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• • Assessment of the Acceptability and Feasibility of Child Potties for Safe Child Feces Disposal in Rural Bangladesh

    Authors: Faruqe Hussain, Stephen P. Luby, Leanne Unicomb, Elli Leontsini, Tania Naushin, Audrey J. Buckland and Peter J. Winch

    Available online: 19 June 2017

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    Indiscriminate defecation among young children and the unsafe disposal of their feces increases fecal contamination in the household environment and the risk of diarrheal disease transmission. Improved sanitary technology for children too young to use a latrine may facilitate safe feces disposal and reduce fecal contamination in the household environment. We assessed the acceptability and feasibility of child potties in rural Bangladesh in 2010. Our team introduced child potties into 26 households for 30 days, and conducted semistructured interviews, group discussions, and observations to assess the acceptability and feasibility of their use for parents and children. Residents of this rural Bangladeshi community accepted the child potties and caregivers found them to be a feasible means of managing child feces. The color, shape, design, and size of the potty influenced its acceptability and use. These residents reported that regular use of the potty improved the household’s physical environment and caregiver and child personal hygiene. Regular potty use also reduced caregivers’ work load by making feces collection and disposal easier. Primary caregivers viewed 4–6 months as the appropriate age to initiate potty training. Sanitation interventions should integrate and emphasize potties for children’s feces management to reduce household environmental contamination.

• • High Iron Levels Are Associated with Increased Malaria Risk in Infants during the First Year of Life in Benin

    Authors: Violeta Moya-Alvarez, Gilles Cottrell, Smaila Ouédraogo, Manfred Accrombessi, Achille Massougbodgi and Michel Cot

    Available online: 19 June 2017

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    The World Health Organization (WHO) estimates that 40% of children in low-income countries are anemic. Therefore, iron supplements are recommended by WHO in areas with high anemia rates. However, some studies have set into question the benefits of iron supplementation in malaria-endemic regions. In Benin, a west African country with high prevalence of anemia and malaria, no iron supplements are given systematically to infants so far despite the WHO recommendations. In this context, we wanted to investigate the effect of iron levels during the first year of life on malarial risk in Benin considering complementary risk factors. We followed 400 women and their offspring between January 2010 and June 2012 in Allada (Benin). Environmental, obstetric, and numerous clinical, maternal, and infant risk factors were considered. In multilevel models, high iron levels were significantly associated with the risk of a positive blood smear (adjusted odds ratio = 2.90, P < 0.001) and Plasmodium falciparum parasitemia (beta estimate = 0.38, P < 0.001). Infants with iron levels in the lowest quartile were less likely to have a positive blood smear (P < 0.001), and the risk increased with higher iron levels. Our results appeal for additional evaluation of the effect of different doses of iron supplements on the infant health status, including malaria incidence. Thus, the health status of infants should be compared between cohorts where iron is given either for prevention or anemia treatment, to better understand the effect of iron supplements on infant health.

• • Epidemiology of Spotted Fever Group Rickettsioses and Acute Undifferentiated Febrile Illness in Villeta, Colombia

    Authors: Álvaro A. Faccini-Martínez, Alejandro Ramírez-Hernández, Christian Barreto, Elkin Forero-Becerra, Diego Millán, Elkin Valbuena, Andrea C. Sánchez-Alfonso, Wilson O. Imbacuán-Pantoja, Jesús A. Cortés-Vecino, Luis J. Polo-Terán, Néstor Yaya-Lancheros, Jorge Jácome, Ana M. Palomar, Sonia Santibáñez, Aránzazu Portillo, José A. Oteo and Marylin Hidalgo

    Available online: 19 June 2017

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    Etiology of acute undifferentiated febrile syndrome (AUFS) is often unknown, leading to inaccurate diagnosis and treatment. Villeta town has been identified as an endemic area for spotted fever group (SFG) rickettsioses but little is known about possible amplifier hosts and other Rickettsia species different from Rickettsia rickettsii. Besides, few studies have approached other AUFS etiologies in the region. We investigated the role of dengue, leptospirosis, rickettsioses, human anaplasmosis, and Q fever as possible causes of AUFS in patients from Villeta. Sera specimens and ticks from animals as well as ticks from vegetation were studied for the presence of different Rickettsia spp. Among 104 sera from patients with AUFS, 16.4%, 24.0%, and 2.9% patients seroconverted to dengue, Leptospira, and SFG Rickettsia, respectively, with a case of probable coinfection or cross-reaction with Anaplasma phagocytophilum. None of the samples were reactive for Coxiella burnetii. Sera samples from 74 horses, 118 dogs, and 62 bovines were collected and showed 33.8%, 14.4%, and 50.0% of seroprevalence for SFG Rickettsia, respectively. A total of 543 ixodid ticks were collected from animals/vegetation and processed in pools for polymerase chain reaction. Among them, 1.7% was positive for Rickettsia genes, and Rickettsia amblyommii, R. rickettsii, and Rickettsia spp. were found. These results confirm the circulation of dengue, different SFG Rickettsia species and the relevance of other etiologies like leptospirosis and human anaplasmosis. Further studies must identify different epidemiological variables to establish proper surveillance and control programs.

• • Mass Azithromycin and Malaria Parasitemia in Niger: Results from a Community-Randomized Trial

    Authors: Kieran S. O’Brien, Sun Y. Cotter, Abdou Amza, Boubacar Kadri, Baido Nassirou, Nicole E. Stoller, Zhaoxia Zhou, Chris Cotter, Sheila K. West, Robin L. Bailey, Philip J. Rosenthal, Bruce D. Gaynor, Travis C. Porco and Thomas M. Lietman

    Available online: 19 June 2017

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    Studies designed to determine the effects of mass administration of azithromycin on trachoma have suggested that mass azithromycin distributions may also reduce the prevalence of malaria. These studies have typically examined the impact of a small number of treatments over short durations. In this prespecified substudy of a cluster-randomized trial for trachoma, we compared malaria parasitemia prevalence in 24 communities in Niger randomized to receive either annual or biannual mass azithromycin distributions over 3 years. The 12 communities randomized to annual azithromycin received three treatments during the high-transmission season, and the 12 communities randomized to biannual azithromycin received a total of six treatments: three during the high-transmission season and three during the low-transmission season. Blood samples were taken to assess malariometric indices among children in all study communities at a single time point during the high-transmission season after 3 years of the intervention. No significant differences were identified in malaria parasitemia, parasite density, or hemoglobin concentration between the annual and biannual treatment arms. When compared with annual mass azithromycin alone, additional mass azithromycin distributions given during the low-transmission season did not significantly reduce the subsequent prevalence of malaria parasitemia or parasite density after 3 years, as measured during the high-transmission season.

• • Human Cases of Tularemia in Armenia, 1996–2012

    Authors: Syuzanna Melikjanyan, Karo Palayan, Artavazd Vanyan, Lilit Avetisyan, Nune Bakunts, Marine Kotanyan and Marta Guerra

    Available online: 19 June 2017

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    A retrospective analysis was conducted of human cases and outbreaks of tularemia in the Republic of Armenia from 1996 to 2012 utilizing Geographic Information System software. A total of 266 human cases of tularemia were recorded in Armenia from 1996 to 2012, with yearly incidence ranging from 0 to 5.5 cases per 100,000 people. Cases predominantly affected the male population (62.8%), 11–20 year age group (37.2%), agricultural workers (49.6%), and persons residing in rural areas (93.6%). In 2003, a waterborne outbreak involving 158 cases occurred in Kotayk Marz, and in 2007, a foodborne outbreak with 17 cases occurred in Gegharkunik Marz, attributed to exposure of food products to contaminated hay. Geospatial analysis of all cases showed that the majority were associated with the steppe vegetation zone, elevations between 1,400 and 2,300 m, and the climate zone associated with dry, warm summers, and cold winters. Characterization of these environmental factors were used to develop a predictive risk model to improve surveillance and outbreak response for tularemia in Armenia.

• • Why Did Zika Not Explode in Cuba? The Role of Active Community Participation to Sustain Control of Vector-Borne Diseases

    Authors: Marta Castro, Dennis Perez, Maria G. Guzman and Clare Barrington

    Available online: 19 June 2017

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    As the global public health community develops strategies for sustainable Zika prevention and control, assessment of the Cuban response to Zika provides critical lessons learned. Cuba’s early and successful response to Zika, grounded in the country’s long-standing dengue prevention and control program, serves as a model of rapid mobilization of intersectoral efforts. Sustaining this response requires applying the evidence generated within the Cuban dengue program that active community participation improves outcomes and is sustainable and cost-effective. There is also a need for implementation science efforts to assess the transferability of lessons learned from Zika prevention and control to other pathogens and from one context to another in addition to how to take these efforts to scale.

• • Classification and Visualization of Physical and Chemical Properties of Falsified Medicines with Handheld Raman Spectroscopy and X-Ray Computed Tomography

    Authors: Tomoko Kakio, Naoko Yoshida, Susan Macha, Kazunobu Moriguchi, Takashi Hiroshima, Yukihiro Ikeda, Hirohito Tsuboi and Kazuko Kimura

    Available online: 19 June 2017

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    Analytical methods for the detection of substandard and falsified medical products (SFs) are important for public health and patient safety. Research to understand how the physical and chemical properties of SFs can be most effectively applied to distinguish the SFs from authentic products has not yet been investigated enough. Here, we investigated the usefulness of two analytical methods, handheld Raman spectroscopy (handheld Raman) and X-ray computed tomography (X-ray CT), for detecting SFs among oral solid antihypertensive pharmaceutical products containing candesartan cilexetil as an active pharmaceutical ingredient (API). X-ray CT visualized at least two different types of falsified tablets, one containing many cracks and voids and the other containing aggregates with high electron density, such as from the presence of the heavy elements. Generic products that purported to contain equivalent amounts of API to the authentic products were discriminated from the authentic products by the handheld Raman and the different physical structure on X-ray CT. Approach to investigate both the chemical and physical properties with handheld Raman and X-ray CT, respectively, promise the accurate discrimination of the SFs, even if their visual appearance is similar with authentic products. We present a decision tree for investigating the authenticity of samples purporting to be authentic commercial tablets. Our results indicate that the combination approach of visual observation, handheld Raman and X-ray CT is a powerful strategy for nondestructive discrimination of suspect samples.

• • Rapid Active Sampling Surveys as a Tool to Evaluate Factors Associated with Acute Gastroenteritis and Norovirus Infection among Children in Rural Guatemala

    Authors: Daniel Olson, Molly M. Lamb, Maria R. Lopez, Maria A. Paniagua-Avila, Alma Zacarias, Gabriela Samayoa-Reyes, Celia Cordon-Rosales and Edwin J. Asturias

    Available online: 19 June 2017

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    We examined burden and factors associated with norovirus (NoV) acute gastroenteritis (AGE) among children in rural Guatemala. Children age 6 weeks to 17 years were enrolled into three AGE surveillance groups, using two-stage cluster sampling: a prospective participatory syndromic surveillance (PSS) cohort and two cross-sectional rapid active sampling (RAS) surveys, conducted from April 2015 to February 2016. Epidemiologic and NoV testing data were used to identify factors associated with NoV infection, AGE, and NoV+ AGE. The three cross-sectional surveys (PSS enrollment visit, RAS Survey 1, and RAS Survey 2) enrolled 1,239 children, who reported 134 (11%) AGE cases with 20% of AGE and 11% of non-AGE samples positive for NoV. Adjusted analyses identified several modifiable factors associated with AGE and NoV infection. The cross-sectional RAS surveys were practical and cost-effective in identifying population-level risk factors for AGE and NoV, supporting their use as a tool to direct limited public health resources toward high-risk populations.

• • Side Benefits of Mass Drug Administration for Lymphatic Filariasis on Strongyloides stercoralis Prevalence on Pemba Island, Tanzania

    Authors: Beatrice Barda, Marco Albonico, Dora Buonfrate, Shaali M. Ame, Said Ali, Benjamin Speich and Jennifer Keiser

    Available online: 19 June 2017

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    Strongyloides stercoralis, although endemic in many countries, is not included in helminth control programs. Few data are available on the prevalence and morbidity linked to this infection. We compared data from two studies conducted in 1998 and 2013 on Pemba Island, Tanzania, involving 525 and 509 schoolchildren, respectively. In 1998, the diagnostic method used was Harada Mori, whereas in 2013 diagnosis was made by both Koga agar plate and Baermann methods. The prevalence registered was 41% in 1998 and 7% in 2013. This data suggest that the prevalence of S. stercoralis on Pemba was significantly reduced 7 years after the last ivermectin administration for preventive chemotherapy and underlines the importance and impact of large-scale preventive chemotherapy, which often goes beyond its actual target. Preventive chemotherapy with ivermectin should be recommended in areas where S. stercoralis is endemic.

• • Population Movement as a Risk Factor for Malaria Infection in High-Altitude Villages of Tahtay–Maychew District, Tigray, Northern Ethiopia: A Case–Ccontrol Study

    Authors: Mebrahtom Haile, Hailemariam Lemma and Yemane Weldu

    Available online: 19 June 2017

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    Key goal and targets of the Ethiopian national malaria control strategy are to achieve malaria elimination within specific geographical areas with historically low malaria transmission and to reach near-zero malaria transmission in the remaining malarious areas by 2020. However, back and forth population movement between high-transmission and low-transmission area imposes challenge on the success of national malaria control programs. Therefore, examining the effect of human movement and identification of at-risk populations is crucial in an elimination setting. A matched case–control study was conducted among 520 study participants at a community level in low malaria transmission settings in northern Ethiopia. Study participants who received a malaria test were interviewed regarding their recent travel history. Bivariate and multivariate analyses were carried out to determine if the reported travel was related to malaria infection. Younger age (adjusted odds ratio [AOR] = 3.20, 95% confidence interval [CI]: 1.73, 5.89) and travel in the previous month (AOR = 11.40, 95% CI: 6.91, 18.82) were statistically significant risk factors for malaria infection. Other statistically significant factors, including lower educational level (AOR = 2.21, 95% CI: 1.26, 3.86) and nonagricultural in occupation (AOR = 2.0, 95% CI: 1.02, 3.94), were also found as risk factors for malaria infection. Generally, travel history was found to be a strong predictor for malaria acquisition in the high-altitude villages. Therefore, besides the existing efforts in endemic areas, targeting those who frequently travel to malarious areas is crucial to reduce malaria infection risks and possibility of local transmissions in high-altitude areas of northern Ethiopia.

• • Diagnostic Validation of the RealStar® Zika Virus Reverse Transcription Polymerase Chain Reaction Kit for Detection of Zika Virus RNA in Urine and Serum Specimens

    Authors: Stephan Ölschläger, Antoine Enfissi, Mareen Zaruba, Mirdad Kazanji and Dominique Rousset

    Available online: 19 June 2017

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    With the Zika virus outbreak in South America starting in 2015 and its potential to cause malformation of the fetus in infected women, the need for diagnostic methods became obvious. Until now, only limited data are available on the diagnostic performance of commercial kits. Here, we present data comparing the RealStar® Zika Virus RT-PCR Kit 1.0 for detection of Zika virus from 208 serum and urine samples collected in French Guiana with a reference method. Of these, 114 samples tested positive with the RealStar Kit and 111 with the reference method.

• • Associations between Household Latrines and the Prevalence of Diarrhea in Idiofa, Democratic Republic of the Congo: A Cross-Sectional Study

    Authors: Seungman Cha, Jae Eun Lee, Dong Sik Seo, Byoung Mann Park, Paul Mansiangi, Jae-sang Hwang and Jungwook Lee

    Available online: 12 June 2017

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    Despite the importance of sanitation, few studies have assessed the effects of latrines on the health outcomes of children under 5 years of age. We assessed the relations between latrine coverage and the prevalence of diarrhea in children under 4 years of age. In this cross-sectional study, we analyzed the baseline data obtained as part of a longitudinal survey targeting 720 households in Idiofa, Bandundu, Democratic Republic of the Congo. We categorized latrines according to the presence of each major component and investigated whether diarrhea prevalence of children under 4 years of age is associated with latrine availability and improvement. Latrines have health benefits regardless of whether they are improved. Also worth noting is that comparatively well-equipped and more appropriately managed latrines could prevent child diarrhea more effectively than less equipped or inappropriately managed latrines. Households who have a latrine with a superstructure, roof, and no flies (a partly improved latrine) were found to be 52% less likely to report cases of diarrhea than households with unimproved latrines (adjusted odds ratio [OR] = 0.48, confidence interval [CI] = 0.31–0.76), which are all the other latrines not included in the partly improved latrine category. We have observed the profound protective effect of latrines with a superstructure. This study demonstrates that latrines are associated with significant improvements in health even when they do not fully meet the conditions of improved latrines. This study adds value to the limited evidence on the effect of latrines on health parameters by demonstrating that latrines have correlations with health benefits regardless of whether they are improved, as well as by elucidating the most essential components of improved latrines.

• • Handwashing in 51 Countries: Analysis of Proxy Measures of Handwashing Behavior in Multiple Indicator Cluster Surveys and Demographic and Health Surveys, 2010–2013

    Authors: Swapna Kumar, Libbet Loughnan, Rolf Luyendijk, Orlando Hernandez, Merri Weinger, Fred Arnold and Pavani K. Ram

    Available online: 12 June 2017

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    In 2009, a common set of questions addressing handwashing behavior was introduced into nationally representative Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS), providing large amounts of comparable data from numerous countries worldwide. The objective of this analysis is to describe global handwashing patterns using two proxy indicators for handwashing behavior from 51 DHS and MICS surveys conducted in 2010–2013: availability of soap anywhere in the dwelling and access to a handwashing place with soap and water. Data were also examined across geographic regions, wealth quintiles, and rural versus urban settings. We found large disparities for both indicators across regions, and even among countries within the same World Health Organization region. Within countries, households in lower wealth quintiles and in rural areas were less likely to have soap anywhere in the dwelling and at designated handwashing locations than households in higher wealth quintiles and urban areas. In addition, disparities existed among various geographic regions within countries. This analysis demonstrates the need to promote access to handwashing materials and placement at handwashing locations in the dwelling, particularly in poorer, rural areas where children are more vulnerable to handwashing-preventable syndromes such as pneumonia and diarrhea.

• • Mycobacterium tuberculosis Infection in Close Childhood Contacts of Adults with Pulmonary Tuberculosis Is Increased by Secondhand Exposure to Tobacco

    Authors: Ifedayo M. O. Adetifa, Lindsay Kendall, Simon Donkor, Moses D. Lugos, Abdulrahman S. Hammond, Patrick K. Owiafe, Martin O. C. Ota, Roger H. Brookes and Philip C. Hill

    Available online: 12 June 2017

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    Tobacco use is a major risk factor for tuberculosis (TB). Secondhand smoke (SHS) is also a risk factor for TB and to a lesser extent, Mycobacterium tuberculosis infection without disease. We investigated the added risk of M. tuberculosis infection due to SHS exposure in childhood contacts of TB cases in The Gambia. Participants were childhood household contacts aged ≤ 14 years of newly diagnosed pulmonary TB (PTB) cases. The intensity of exposure to the case was categorized according to whether contacts slept in the same room, same house, or a different house as the case. Contacts were tested with an enzyme-linked immunospot interferon gamma release assay. In multivariate regression models, M. tuberculosis infection was associated with increasing exposure to a case (odds ratios [OR]: 3.9, 95% confidence interval [CI]: 2.11–71.4, P < 0.001]) and with male gender (OR: 1.5 [95% CI: 1.12–2.11], P = 0.008). Tobacco use caused a 3-fold increase in the odds of M. tuberculosis infection in children who slept closest to a case who smoked within the same home compared with a nonsmoking case (OR: 8.0 [95% CI: 2.74–23.29] versus 2.4 [95% CI: 1.17–4.92], P < 0.001). SHS exposure as an effect modifier appears to greatly increase the risk of M. tuberculosis infection in children exposed to PTB cases. Smoking cessation campaigns may be important for reducing transmission of M. tuberculosis to children within households.

• • Bartonella Infection in Hematophagous, Insectivorous, and Phytophagous Bat Populations of Central Mexico and the Yucatan Peninsula

    Authors: Matthew J. Stuckey, Bruno B. Chomel, Guillermo Galvez-Romero, José Ignacio Olave-Leyva, Cirani Obregón-Morales, Hayde Moreno-Sandoval, Nidia Aréchiga-Ceballos, Mónica Salas-Rojas and Alvaro Aguilar-Setién

    Available online: 12 June 2017

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    Although emerging nonviral pathogens remain relatively understudied in bat populations, there is an increasing focus on identifying bat-associated bartonellae around the world. Many novel Bartonella strains have been described from both bats and their arthropod ectoparasites, including Bartonella mayotimonensis, a zoonotic agent of human endocarditis. This cross-sectional study was designed to describe novel Bartonella strains isolated from bats sampled in Mexico and evaluate factors potentially associated with infection. A total of 238 bats belonging to seven genera were captured in five states of Central Mexico and the Yucatan Peninsula. Animals were screened by bacterial culture from whole blood and/or polymerase chain reaction of DNA extracted from heart tissue or blood. Bartonella spp. were isolated or detected in 54 (22.7%) bats, consisting of 41 (38%) hematophagous, 10 (16.4%) insectivorous, and three (4.3%) phytophagous individuals. This study also identified Balantiopteryx plicata as another possible bat reservoir of Bartonella. Univariate and multivariate logistic regression models suggested that Bartonella infection was positively associated with blood-feeding diet and ectoparasite burden. Phylogenetic analysis identified a number of genetic variants across hematophagous, phytophagous, and insectivorous bats that are unique from described bat-borne Bartonella species. However, these strains were closely related to those bartonellae previously identified in bat species from Latin America.

• • Malaria-Associated Mortality in the Australian Defence Force during the Twentieth Century

    Author: G. Dennis Shanks

    Available online: 12 June 2017

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    Malaria has been a military problem throughout history capable of causing epidemics that stop military operations. Individual mortality was examined from records of the three major wars of the 20th century that involved Australia in which 133 (1914–1919), 92 (1943–1945), and two (1965–1967) soldiers are known to have died with malaria. Those dying were predominately enlisted soldiers with a mean age of 29 years often complicated by other infections such as influenza pneumonia or scrub typhus. Lethal epidemics of falciparum malaria occurred in Palestine/Syria in October 1918 and New Guinea in September 1943 to March 1944. Although no Australian soldier has died in nearly 50 years from malaria, there were three serious falciparum infections in soldiers in East Timor 1999–2000 who might have died if intensive care had not been provided. Recent military deployments into Africa including United Nations contingents still show falciparum malaria’s lethality despite the availability of effective malaria chemoprophylaxis.

• • Rocky Mountain Spotted Fever and Pregnancy: Four Cases from Sonora, Mexico

    Authors: Jesus David Licona-Enriquez, Jesus Delgado-de la Mora, Christopher D. Paddock, Carlos Arturo Ramirez-Rodriguez, María del Carmen Candia-Plata and Gerardo Álvarez Hernández

    Available online: 12 June 2017

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    We present a series of four pregnant women with Rocky Mountain spotted fever (RMSF) that occurred in Sonora, Mexico, during 2015–2016. Confirmatory diagnoses were made by polymerase chain reaction or serological reactivity to antigens of Rickettsia rickettsii by using an indirect immunofluorescence antibody assay. Each patient presented with fever and petechial rash and was treated successfully with doxycycline. Each of the women and one full-term infant delivered at 36 weeks gestation survived the infection. Three of the patients in their first trimester of pregnancy suffered spontaneous abortions. RMSF should be suspected in any pregnant woman presenting with fever, malaise and rash in regions where R. rickettsii is endemic.

• • Assessing the Short-Term Global Health Experience: A Cross-Sectional Study of Demographics, Socioeconomic Factors, and Disease Prevalence

    Authors: Olivia Geen, Allison Pumputis, Cristina Kochi, Andrew Costa and Karl Stobbe

    Available online: 12 June 2017

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    Interest in short-term global health experiences to underserviced populations has grown rapidly in the last few decades. However, there remains very little research on what participants can expect to encounter. At the same time, it has been suggested that in order for physicians and workers to provide safe and effective care, volunteers should have a basic understanding of local culture, health systems, epidemiology, and socioeconomic needs of the community before arriving. Our objective was to add to the limited literature on what short-term global health trips can expect to encounter through a cross-sectional study of patient demographics, socioeconomic markers, and the prevalence of diseases encountered on a short-term medical service trip to Lima, Peru. Descriptive analysis was conducted on clinic data collected from patients living in Pamplona Alta and Pamplona Baja, Lima, Peru, in July 2015. We found that volunteers encountered mainly female patients (70.8%), and that there were significant socioeconomic barriers to care including poverty, poor housing, environmental exposures, and lack of continuity of health care. Analysis of the disease prevalence found a high proportion of acute and chronic musculoskeletal pain in the adult populations (18.8% and 11.4%, respectively), and a high presentation of upper respiratory tract infections (25.4%) and parasites (22.0%) in the pediatric group. These findings can be used by future short-term medical service trips to address potential gaps in care including the organization of weekend clinics to allow access to working men, and the use of patient education and nonpharmacological management of acute and chronic disease.

• • Evaluation of Onchocerciasis Transmission in Tanzania: Preliminary Rapid Field Results in the Tukuyu Focus, 2015

    Authors: Heather N. Paulin, Andreas Nshala, Akili Kalinga, Upendo Mwingira, Ryan Wiegand, Vitaliano Cama and Paul T. Cantey

    Available online: 12 June 2017

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    To compare diagnostic tests for onchocerciasis in a setting that has suppressed transmission, a randomized, age-stratified study was implemented in an area in Tanzania that had received 15 rounds of annual mass drug administration (MDA) with ivermectin. Study participants (N = 948) from 11 villages underwent a questionnaire, skin examination, skin snips, and blood draw. The burden of symptomatic disease was low. Ov-16 antibody rapid diagnostic test (RDT) results were positive in 38 (5.5%) participants, with 1 (0.5%), 1 (0.4%), and 2 (0.8%) in children aged 0–5, 6–10, and 11–15 years, respectively. Despite significant impact of MDA on transmission, the area would have failed to meet World Health Organization serologic criteria for stopping MDA if a full evaluation had been conducted. The specificity of the RDT, which is 97–98%, may result in the identification of a number of false positives that would exceed the current stop MDA threshold.

• • Identification of Risk Factors Associated with Transmission of Plague Disease in Eastern Zambia

    Authors: Stanley S. Nyirenda, Bernard M. Hang’ombe, Robert Machangu, Jackson Mwanza and Bukheti S. Kilonzo

    Available online: 12 June 2017

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    Plague is a fatal, primarily rodent-flea-borne zoonotic disease caused by Yersinia pestis. The identification of risk factors of plague was investigated through questionnaire interview and conducting focus group discussion (FGD) in Sinda and Nyimba of eastern Zambia. A total of 104 questionnaires were administered to individual respondents and 20 groups consisting of 181 discussants, which comprised FGD team in this study. The study revealed that trapping, transportation, and preparation of rodents for food exposed the community to rodent and their fleas suggesting that plague may have occurred primarily by either flea bites or contact with infected wild rodents. The study also revealed that most people in communities consumed rodents as part of their regular diet; therefore, contact with small wild mammals was a common practice. The mode of transportation of freshly trapped rodents, in particular, carcasses risked human to flea bites. Questionnaire respondents (75%) and FGD discussants (55%) indicated that trappers preferred to carry rodent carcasses in small bags, whereas 55.8% and 20% respectively, reported hunters carrying carcasses in their pockets. Carrying of carcass skewers on trappers’ shoulders was reported by 38.4% and 20% of individual respondents and FGD, respectively. All these activities were exposing humans to rodents and their fleas, the natural reservoirs and vectors of plague, respectively. This study also showed that there is a statistically significant (χ2 = 4.6878, P < 0.05), between digging of rodents from their burrows and the presence of fleas on the hunter’s bodies or clothes, which exposes humans to potentially flea bites in an enzootic cycle.

• • Serological Evidence of Rickettsia spp. in Western Australian Dogs

    Authors: Mark David Bennett, Mohammad Yazid Abdad and John Stenos

    Available online: 12 June 2017

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    It has been claimed that dogs can be useful sentinels for public health monitoring of vector-borne infectious diseases, including Rickettsia spp. We used 153 canine blood samples opportunistically collected at Murdoch University Veterinary Hospital and 156 canine sera collected from Aboriginal communities in northwest Western Australia to test for evidence of Rickettsia spp. exposure, using microimmunofluorescence (MIF) in the latter case, and both MIF and polymerase chain reaction (PCR) in the former. Conventional and real-time PCR failed to amplify any Rickettsia spp. DNA. The seroprevalence for spotted fever group/transitional group Rickettsia spp. in Western Australian dogs was 17.3% (54/312), and for typhus group (TG) Rickettsia spp., 18.4% (57/310), with a cut-off titer of 1:128. Young dogs (≤ 2 years) from Aboriginal communities had significantly lower seropositivity to TG Rickettsia spp. compared with all other groups, and young Perth dogs had a significantly higher seropositivity to TG Rickettsia spp. than all Aboriginal community dogs.

• • A Qualitative Study of Provider Perceptions of Influences on Uptake of Pediatric Hospital Guidelines in Lao PDR

    Authors: Amy Z. Gray, Douangdao Soukaloun and Bandith Soumphonphakdy

    Available online: 12 June 2017

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    Strategies to improve the quality of hospital care are needed if ongoing gains in child health and survival are to be made. We previously reported on improvements in the quality of case management in hospitals following a guideline-based intervention in Lao PDR, with variation in the degree of change achieved between clinical conditions. This study aims to understand the factors that influenced the uptake of the guideline-based intervention, and its impact on care. This qualitative study was embedded in a mixed-methods evaluation of guideline implementation in nine hospitals in Lao PDR. Focus groups and individual interviews were conducted with 70 health staff from central, provincial, and district hospitals. The interview guide was based on the Theoretical Domains Framework. Inductive content analysis was performed on interview transcripts to identify themes, supported by field notes from the intervention. Findings were triangulated against previously reported quantitative outcomes using driver diagrams. Key influences on guidelines uptake related to the guideline and intervention (filling a void, physical accessibility, comprehensibility, training in guideline use), health staff (behavior regulation, trust in guidelines, and beliefs about consequences), and the environment (social influences particularly consensus and incorporation into clinical norms). The major barrier was family preference for treatments in conflict with guideline recommendations. This study identifies contextual factors that explain, as well as validate previously identified improvements in care following guideline implementation in Lao PDR. It provides novel understanding of why the same intervention may have a differential impact on different clinical conditions.

• • Differences in Mortality and Clinical Manifestations of Dengue Hemorrhagic Fever in Taiwan in Different Years: A Comparison for Cases in 2014 and 2015 Epidemics

    Authors: Ko Chang, Chung-Hao Huang, Ing-Kit Lee, Po-Liang Lu, Chun-Yu Lin, Tun-Chieh Chen, Ping-Chang Lai, Hsiao-Cheng Hsieh, Hsin-Liang Yu, Chih-Hsing Hung, Meng-Chieh Wu, Yi-Ying Chin, Chun-Chi Huang, Deng-Chyang Wu and Yen-Hsu Chen

    Available online: 12 June 2017

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    People in southern Taiwan experienced two major dengue outbreaks in 2014 and 2015. The mortality and clinical features were very different between these 2 years. Dengue virus serotype 1 (DENV-1) caused epidemic outbreak in 2014 and DENV-2 was predominant in 2015. The characteristics of dengue hemorrhagic fever (DHF) cases in the 2 years was analyzed. We conducted a retrospective chart review to analyze the clinical and laboratory features of 206 adult patients with DHF in southern Taiwan in 2014 and 2015. The mortality rate of DHF cases in 2015 was higher than that of cases in 2014 (38.7% versus 12.4%, P < 0.0001). Compared with cases in 2014, DHF cases in 2015 had more complications, such as gastrointestinal bleeding (78.5% versus 61.9%, P = 0.01), severe hepatitis (30.1% versus 8%, P < 0.0001), and myocarditis (14% versus 0.9%, P < 0.0001). Among the mortality cases, diabetes, chronic renal failure, proton-pump inhibitors using, platelet transfusion, and Charlson comorbidity index score (Charlson score) were also higher in 2015. Multivariate analysis for the mortality cases revealed that the risk factors were Charlson score ≥ 5 (P = 0.02, odds ratio [OR] = 4.07, 95% confidence interval [CI] = 1.244–13.307), severe hepatitis (P < 0.0001, OR = 11.97, 95% CI = 3.831–37.396), and acute renal failure (P < 0.0001, OR = 98.76, 95% CI = 10.847–899.22). DHF cases in 2015 had higher mortality and more complications, such as gastrointestinal bleeding, severe hepatitis, and myocarditis, than in 2014 in southern Taiwan. In the 2-year DHF case series, Charlson score ≥ 5, severe hepatitis, and acute renal failure were independent significant variables for mortality.

• • Recurrence of Guinea Worm Disease in Chad after a 10-Year Absence: Risk Factors for Human Cases Identified in 2010–2011

    Authors: Nandini Sreenivasan, Adam Weiss, Jean-Paul Djiatsa, Fernand Toe, Ngarodjel Djimadoumaji, Tracy Ayers, Mark Eberhard, Ernesto Ruiz-Tiben and Sharon Roy

    Available online: 12 June 2017

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    A decade after reporting its last case of Guinea worm disease (GWD), a waterborne parasitic disease targeted for eradication, Chad reported 20 confirmed human cases from 17 villages—10 cases in 2010 and 10 cases in 2011. In 2012, the first GWD dog infections were diagnosed. We conducted a case-control study during April–May 2012 to identify human transmission risk factors and epidemiologic links. We recruited 19 cases and 45 controls matched by age, sex, time, and location of exposure based on the case patients’ periods of infection 10–14 months earlier. Data were analyzed with simple conditional logistic regression models using Firth penalized likelihood methods. Unusually, GWD did not appear to be associated with household primary water sources. Instead, secondary water sources, used outside the village or other nonprimary sources used at home, were risk factors (matched odds ratio = 38.1, 95% confidence interval = 1.6–728.2). This study highlights the changing epidemiology of GWD in Chad—household primary water sources were not identified as risk factors and few epidemiologic links were identified between the handfuls of sporadic cases per year, a trend that continues. Since this investigation, annual dog infections have increased, far surpassing human cases. An aquatic paratenic host is a postulated mode of transmission for both dogs and humans, although fish could not be assessed in this case-control study due to their near-universal consumption. GWD’s evolving nature in Chad underscores the continued need for interventions to prevent both waterborne and potential foodborne transmission until the true mechanism is established.

• • The Role of Risk Proximity in the Beliefs and Behaviors Related to Mosquito-Borne Diseases: The Case of Chikungunya in French Guiana

    Authors: Claude Flamand, Camille Fritzell, Pauline Obale, Philippe Quenel and Jocelyn Raude

    Available online: 12 June 2017

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    Human behaviors are increasingly recognized to play a key role in the spread of infectious diseases. Although a set of social and cognitive determinants has been consistently found to affect the adoption of health protective behaviors aiming to control and prevent a variety of infections, little is currently known about the ecological drivers of these behaviors in epidemic settings. In this article, we took advantage of the outbreak of chikungunya, a reemerging mosquito-borne disease, that occurred in French Guiana in 2014–15 to test empirically the assumption proposed by Zielinski-Gutierrez and Hayden that the proximity of the disease and perceptions of the natural environment may considerably shape public response to an emerging health threat. To achieve this, a cross-sectional survey was conducted among high school students of the region (N = 1462) at an early stage of the epidemic. Surprisingly, spatial analysis of the collected data leads to counterintuitive results as the participants who lived in the most affected area expressed less concern about the disease and practiced preventive behaviors less frequently than did other participants. These paradoxical results may be attributed to the possible activation of risk denial processes which have previously been observed in the risk perception literature, and described by several social and psychological defensiveness theories.

• • The Effects of an Integrated Community Case Management Strategy on the Appropriate Treatment of Children and Child Mortality in Kono District, Sierra Leone: A Program Evaluation

    Authors: Ruwan Ratnayake, Jeffrey Ratto, Colleen Hardy, Curtis Blanton, Laura Miller, Mary Choi, John Kpaleyea, Pheabean Momoh and Yolanda Barbera

    Available online: 12 June 2017

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    Integrated community case management (iCCM) aims to reduce child mortality in areas with poor access to health care. iCCM was implemented in 2009 in Kono district, Sierra Leone, a postconflict area with high under-five mortality rates (U5MRs). We evaluated iCCM’s impact and effects on child health using cluster surveys in 2010 (midterm) and 2013 (endline) to compare indicators on child mortality, coverage of appropriate treatment, timely access to care, quality of care, and recognition of community health workers (CHWs). The sample size was powered to detect a 28% decline in U5MR. Clusters were selected proportional to population size. All households were sampled to measure mortality and systematic random sampling was used to measure coverage in a subset of households. We used program data to evaluate utilization and access; 5,257 (2010) and 3,649 (2013) households were surveyed. U5MR did not change significantly (4.54 95% confidence interval [CI]: 3.47–5.60] to 3.95 [95% CI: 3.06–4.83] deaths per 1,000 per month (P = 0.4)) though a relative change smaller than 28% could not be detected. CHWs were the first source of care for 52% (2010) and 50.9% (2013) of children. Coverage of appropriate treatment of fever by CHWs or peripheral health units increased from 45.5% [95% CI: 39.2–52.0] to 58.2% [95% CI: 50.5–65.5] (P = 0.01); changes for diarrhea and pneumonia were not significant. The continued reliance on the CHW as the first source of care and improved coverage for the appropriate treatment of fever support iCCM’s role in Kono district.

• • Control of Human Echinococcosis in Xinjiang, China, with 2,544 Surgeries in a Multihospital Network

    Authors: Xinhua Chen, Xinyu Duan, Yingmei Shao, Jianwen Jiang, Shusen Zheng and Hao Wen

    Available online: 12 June 2017

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    Human echinococcosis is a serious parasitic disease threatening public health worldwide especially in Xinjiang, China, an undeveloped farming and pastoral area. A multihospital surgical network was applied to improve human echinococcosis control. An innovative surgery network connected the 28 designated public hospitals, which distributed in a vast land of 1,600,000 m2. The surgery network integrated the efficient patient digital information sharing, treatment consulting, patient transfer, and financial support. The 6-year practical outcome of 2,544 surgeries in Xinjiang, China, was retrospectively analyzed. Electronic database and surgery network have been proven especially effective in undeveloped area with vast territory, sparse population, multiple languages, and poor traffic conditions. This network turned out effectively improved patient processing efficiency and decreased the medical cost.

• • Dengue Virus Coinfection in Human Immunodeficiency Virus-1-Infected Patients on the West Coast of Mexico

    Authors: Francisco Espinoza-Gómez, Iván Delgado-Enciso, Salvador Valle-Reyes, Rodolfo Ochoa-Jiménez, Conrado Arechiga-Ramírez, José L. Gámez-Arroyo, Roberto Vázquez-Campuzano, Carmen Guzmán-Bracho, Clemente Vásquez and Uriel A. López-Lemus

    Available online: 12 June 2017

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    Dengue virus infection in human immunodeficiency virus (HIV)-positive patients is not well studied. Previous reports suggest a transitory inhibition of the HIV-1 viral load, as well as a benign clinical progression of dengue. The follow-up of six HIV-1-infected patients, diagnosed and hospitalized with dengue virus infection in the State of Colima, Mexico, was carried out to analyze the progression of this viral coinfection. The presence of dengue virus serotype 1 was confirmed through molecular tests. No severe complications were observed in any of the patients during dengue virus infection. Significant alteration of the HIV-1 viral loads was not observed during dengue virus infection and 6 months after coinfection. Further studies are required to understand the pathology, as well as the clinical course, of these viral coinfections.

• • Respiratory Complications of Plasmodium vivax Malaria: Systematic Review and Meta-Analysis

    Authors: Fernando Val, Kim Machado, Lisiane Barbosa, Jorge Luis Salinas, André Machado Siqueira, Maria Graças Costa Alecrim, Hernando del Portillo, Quique Bassat, Wuelton Marcelo Monteiro and Marcus Vinícius Guimarães Lacerda

    Available online: 12 June 2017

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    Malaria, a major global public health problem, is mainly caused by Plasmodium falciparum and Plasmodium vivax, and is responsible for nearly half a million deaths annually. Although P. vivax malaria was not believed to cause severe disease, recent robust studies have proved otherwise. However, the clinical spectrum and pathogenesis of severe vivax malaria and, especially, its respiratory complications remain poorly understood. A systematic search for articles reporting respiratory complications associated with vivax malaria was performed in Lilacs, Cochrane, Scielo, Web of Science, and Medline databases irrespective of publication date. Prevalence of acute respiratory distress syndrome (ARDS) and associated mortality among vivax patients were calculated from cross-sectional and longitudinal studies, whereas factors associated with mortality were calculated from data pooled from case reports and series of cases. A total of 101 studies were included (49 cross-sectional or longitudinal and 52 case reports or series of cases). Prevalence of ARDS was 2.8% and 2.2% in children and adults, respectively, with nearly 50% mortality. Moreover, female sex (P = 0.013), having any comorbidity (P = 0.036), lower body temperature (P = 0.032), lower hemoglobin (P = 0.043), and oxygen saturation (P = 0.053) values were significantly associated with mortality. Plasmodium vivax malaria respiratory complications included ARDS and were associated with high mortality. Demographics and clinical characteristics upon presentation to hospital were associated with mortality among patients with respiratory complications in vivax malaria. This study reaffirms the evidence of severe and fatal complications of P. vivax malaria and its associated respiratory complications.

• • Ocular Gnathostomiasis—Update of Earlier Survey

    Authors: Yukifumi Nawa, Masahide Yoshikawa, Kittisak Sawanyawisuth, Verajit Chotmongkol, Sandra Fernández Figueiras, Maria Benavides and Sylvia Paz Diaz Camacho

    Available online: 12 June 2017

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    Ocular gnathostomiasis is rather a rare food-borne zoonosis caused by infection with the larvae of several species of genus Gnathostoma and is a representative ocular larva migrans syndrome. In our previous literature survey, we found 73 cases of ocular gnathostomiasis reported up to and including 2009, though additional sporadic cases have been reported in Asia and the Americas since that report. Here, we review 10 additional cases reported since 2010, and also update current findings regarding epidemiological and clinical features in affected patients.

• • Case Report: Disseminated Shewanella algae Infection with Meningoencephalitis in a Traveler Secondary to Marine Injury in Madagascar

    Authors: Caroline Brulliard, Nicolas Traversier, Jérôme Allyn, Christopher Schaeffer, Bruno Bouchet and Nicolas Allou

    Available online: 12 June 2017

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    Marine microorganisms such as Shewanella spp., Vibrio spp., and Aeromonas spp. can cause sepsis secondary to a wound infection in the context of swimming. These microorganisms are most often susceptible to fluoroquinolones. Here, we report a unique case of Shewanella algae bacteremia associated with meningoencephalitis and disseminated via hematogenous spread secondary to a skin injury. The patient suffered the injury while swimming in saline water during a cruise holiday in Madagascar, and she was initially treated with amoxicillin. The neurological evolution was unsatisfactory. Better knowledge of such infections (and especially of the context in which they occur), as well as greater familiarity with the susceptibility profile of different marine microorganisms would have allowed health professionals to provide presumptive microbiological diagnosis and effective treatment earlier.

• • Rabies in Myanmar: Prevalent, Preventable but not Prioritized

    Authors: Thet Thet Mu, Aye Aye Sein, Chit Soe, Nan Phyu Phyu Aung, Tint Tint Kyi and Josh Hanson

    Available online: 12 June 2017

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    Despite the availability of proven measures to prevent the disease, rabies now kills more people in Myanmar than malaria. Although there are challenges in controlling rabies in such a large and culturally diverse country, Myanmar’s successful National Malaria Control Program demonstrates what can be achieved with sufficient political, financial, and scientific commitment. Presently, however, Myanmar lacks a comparable program to coordinate the multifaceted approach that is necessary to control rabies. The national government has invested heavily in improving access to postexposure prophylaxis, but there should also be an emphasis on other, more cost-effective strategies, particularly mass canine vaccination, which has been an essential component of successful rabies elimination programs in other countries. Continued health system strengthening is also required to improve primary health care, whereas decentralization of laboratory diagnostic services is needed to facilitate more timely, rational, and cost-effective use of postexposure prophylaxis.

• • Estimating the Added Utility of Highly Sensitive Histidine-Rich Protein 2 Detection in Outpatient Clinics in Sub-Saharan Africa

    Authors: Mateusz M. Plucinski, Eric Rogier, Pedro Rafael Dimbu, Filomeno Fortes, Eric S. Halsey and Michael Aidoo

    Available online: 12 June 2017

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    Most malaria testing is by rapid diagnostic tests (RDTs) that detect Plasmodium falciparum histidine-rich protein 2 (HRP2). Recently, several RDT manufacturers have developed highly sensitive RDTs (hsRDTs), promising a limit of detection (LOD) orders of magnitude lower than conventional RDTs. To model the added utility of hsRDTs, HRP2 concentration in Angolan outpatients was measured quantitatively using an ultrasensitive bead-based assay. The distribution of HRP2 concentration was bimodal in both afebrile and febrile patients. The conventional RDT was able to detect 81% of all HRP2-positive febrile patients and 52–77% of HRP2-positive afebrile patients. The added utility of hsRDTs was estimated to be greater in afebrile patients, where an hsRDT with a LOD of 200 pg/mL would detect an additional 50–60% of HRP2-positive persons compared with a conventional RDT with a LOD of 3,000 pg/mL. In febrile patients, the hsRDT would detect an additional 10–20% of cases. Conventional RDTs already capture the vast majority of symptomatic HRP2-positive individuals, and hsRDTs would have to reach a sufficiently low LOD approaching 200 pg/mL to provide added utility in identifying HRP2-positive, asymptomatic individuals.

• • A Recombinant 47-kDa Outer Membrane Protein Induces an Immune Response against Orientia tsutsugamushi Strain Boryong

    Authors: Sangho Choi, Hang Jin Jeong, Kyu-Jam Hwang, Byoungchul Gill, Young Ran Ju, Yeong Seon Lee and Jeongmin Lee

    Available online: 05 June 2017

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    We investigated the 47-kDa outer membrane protein (OMP), which is a periplasmic serine protease and an antigenic major surface protein of Orientia tsutsugamushi, as a vaccine candidate. We developed a conventional subunit vaccine expressing recombinant 47-kDa OMP (rec47) and a DNA vaccine (p47). In mouse immunization experiments, intranasal immunization with rec47 alone or with rec47 plus heat-labile enterotoxin B subunit from Escherichia coli or plus cholera toxin (CT) as adjuvants induced a higher amount of rec47-specific antibodies than intramuscular immunization with p47 alone or with p47 plus pBOOST2-samIRF7/3 (pB) as adjuvant. Moreover, the combination of rec47 and CT induced a strong cellular immune response to 47-kDa OMP, as demonstrated by a spleen cell proliferation assay, and also induced Th1- and Th2-type cytokine production, as demonstrated by a cytokine enzyme-linked immunosorbent assay. Intranasal immunization with rec47 plus CT was the most effective method for the induction of humoral and cell-mediated immune responses. Furthermore, relatively strong protection against homologous O. tsutsugamushi strain Boryong challenge was observed in mice immunized with rec47 plus CT. Therefore, 47-kDa OMP is an attractive candidate for developing a prophylactic vaccine against scrub typhus by O. tsutsugamushi infection.

• • High Mortality and Coinfection in a Prospective Cohort of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Patients with Histoplasmosis in Guatemala

    Authors: Blanca Samayoa, Monika Roy, Angela Ahlquist Cleveland, Narda Medina, Dalia Lau-Bonilla, Christina M. Scheel, Beatriz L. Gomez, Tom Chiller and Eduardo Arathoon

    Available online: 05 June 2017

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    Histoplasmosis is one of the most common and deadly opportunistic infections among persons living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome in Latin America, but due to limited diagnostic capacity in this region, few data on the burden and clinical characteristics of this disease exist. Between 2005 and 2009, we enrolled patients ≥ 18 years of age with suspected histoplasmosis at a hospital-based HIV clinic in Guatemala City. A case of suspected histoplasmosis was defined as a person presenting with at least three of five clinical or radiologic criteria. A confirmed case of histoplasmosis was defined as a person with a positive culture or urine antigen test for Histoplasma capsulatum. Demographic and clinical data were also collected and analyzed. Of 263 enrolled as suspected cases of histoplasmosis, 101 (38.4%) were confirmed cases. Median time to diagnosis was 15 days after presentation (interquartile range [IQR] = 5–23). Crude overall mortality was 43.6%; median survival time was 19 days (IQR = 4–69). Mycobacterial infection was diagnosed in 70 (26.6%) cases; 26 (25.7%) histoplasmosis cases were coinfected with mycobacteria. High mortality and short survival time after presentation were observed in patients with histoplasmosis. Mycobacterial coinfection diagnoses were frequent, highlighting the importance of pursuing diagnoses for both diseases.

• • Precisely Tracking Childhood Death

    Authors: Tamer H. Farag, Jeffrey P. Koplan, Robert F. Breiman, Shabir A. Madhi, Penny M. Heaton, Trevor Mundel, Jaume Ordi, Quique Bassat, Clara Menendez and Scott F. Dowell

    Available online: 05 June 2017

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    Little is known about the specific causes of neonatal and under-five childhood death in high-mortality geographic regions due to a lack of primary data and dependence on inaccurate tools, such as verbal autopsy. To meet the ambitious new Sustainable Development Goal 3.2 to eliminate preventable child mortality in every country, better approaches are needed to precisely determine specific causes of death so that prevention and treatment interventions can be strengthened and focused. Minimally invasive tissue sampling (MITS) is a technique that uses needle-based postmortem sampling, followed by advanced histopathology and microbiology to definitely determine cause of death. The Bill & Melinda Gates Foundation is supporting a new surveillance system called the Child Health and Mortality Prevention Surveillance network, which will determine cause of death using MITS in combination with other information, and yield cause-specific population-based mortality rates, eventually in up to 12–15 sites in sub-Saharan Africa and south Asia. However, the Gates Foundation funding alone is not enough. We call on governments, other funders, and international stakeholders to expand the use of pathology-based cause of death determination to provide the information needed to end preventable childhood mortality.

• • Severe and Complicated Cynomolgi Malaria in a Rhesus Macaque Resulted in Similar Histopathological Changes as Those Seen in Human Malaria

    Authors: Chester Joyner, The MaHPIC Consortium, Jennifer S. Wood, Alberto Moreno, Anapatricia Garcia and Mary R. Galinski

    Available online: 05 June 2017

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    Histopathological data collected from patients with severe malaria have been instrumental for studying malaria pathogenesis. Animal models of malaria are critical to complement such studies. Here, the histopathological changes observed in a rhesus macaque with severe and complicated Plasmodium cynomolgi malaria are reported. The animal presented with thrombocytopenia, severe anemia, and hyperparasitemia during the acute infection. The macaque was given subcurative antimalarial treatment, fluid support, and a blood transfusion to treat the clinical complications, but at the time of transfusion, kidney function was compromised. These interventions did not restore kidney function, and the animal was euthanized due to irreversible renal failure. Gross pathological and histological examinations revealed that the lungs, kidneys, liver, spleen, and bone marrow exhibited abnormalities similar to those described in patients with malaria. Overall, this case report illustrates the similarities in the pathophysiological complications that can occur in human malaria and cynomolgi malaria in rhesus macaques.

• • First Report on Natural Infection of Phlebotomus sergenti with Leishmania tropica in a Classical Focus of Leishmania major in Tunisia

    Authors: Kaouther Jaouadi, Jihene Bettaieb, Amira Bennour, Sadek Salem, Mohamed Ridha Rjeibi, Sana Chaabane, Rihab Yazidi, Neila Khabouchi, Adel Gharbi and Afif Ben Salah

    Available online: 05 June 2017

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    In Tunisia, chronic cutaneous leishmaniasis due to Leishmania tropica is an important health problem. Its spreading has not been fully elucidated. Information on sandfly vectors, as well as their associated Leishmania species, is of paramount importance since vector dispersion is one of the major factors responsible for pathogen dissemination. Ninety-seven unfed females belonging to the genera Sergentomyia and Phlebotomus were collected between June and August 2015 using sticky paper traps. Polymerase chain reaction–restriction fragment length polymorphism analysis of the internal transcribed spacer 1and sequencing were used for Leishmania detection and identification. In total, 650 sandflies were captured and identified (380 males and 270 females). Ninety-seven unfed females were tested for the presence of Leishmania parasite DNA. Six Phlebotomus sergenti were found positive for L. tropica. This novel finding enhances the understanding of the cycle extension of L. tropica outside its original focus of Tataouine.

• • Prevalence, Age Profile, and Associated Risk Factors for Hymenolepis nana Infection in a Large Population-Based Study in Northern Peru

    Authors: Percy M. Vilchez-Barreto, Ricardo Gamboa, Saul Santivañez, Seth E. O'Neal, Claudio Muro, Andrés G. Lescano, Luz-Maria Moyano, Guillermo Gonzálvez, Hector H. García and for the Cysticercosis Working Group in Perú (CWGP)

    Available online: 05 June 2017

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    Hymenolepis nana, the dwarf tapeworm, is a common intestinal infection of children worldwide. We evaluated infection and risk factor data that were previously collected from 14,761 children aged 2–15 years during a large-scale program in northern Peru. We found that 1,124 of 14,761 children (7.61%) had H. nana infection, a likely underestimate given that only a single stool sample was examined by microscopy for diagnosis. The strongest association with infection was lack of adequate water (adjusted prevalence ratio [aPR] 2.22, 95% confidence interval [CI] 1.82–2.48) and sanitation infrastructure in the house (aPR 1.94, 95% CI 1.64–2.29). One quarter of those tested did not have a bathroom or latrine at home, which doubled their likelihood of infection. Similarly, one quarter did not have piped public water to the house, which also increased the likelihood of infection. Continued efforts to improve access to basic water and sanitation services will likely reduce the burden of infection in children for this and other intestinal infections.

• • Therapeutic Response in Adult Patients with Nonsevere Chronic Paracoccidioidomycosis Treated with Sulfamethoxazole–Trimethoprim: A Retrospective Study

    Authors: Andreia F. Nery, Natasha P. Crepaldi, Soraya B. R. S. Rossi, Tomoko Tadano, Fabio A. Leal-Santos, Rosane Christine Hahn, Valfredo M. Menezes and Cor Jesus F. Fontes

    Available online: 30 May 2017

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    According to the Brazilian Consensus on Paracoccidioidomycosis (PCM), itraconazole is the drug of choice for treatment. However, the combination of sulfamethoxazole and trimethoprim (SMX-TMP) is most commonly used in clinical practice because of its higher availability in the public health services. The aims of this study were to evaluate the therapeutic response of patients with nonsevere chronic PCM to SMX-TMP and highlight the factors related to treatment failure. An adequate therapeutic response was defined as completely improved disease signs and symptoms after medication use for a minimum of 6 months, followed by normalized hematological and biochemical changes, radiological improvements, and negative mycological examination findings. Medical records were analyzed for 244 patients with nonsevere chronic PCM who were treated between 1998 and 2014. In total, 41.9% of the patients had PCM for ≥ 8 months. Seven (2.9%) patients were coinfected with human immunodeficiency virus (HIV). The median (25%, 75% percentiles) treatment duration was 21 (10, 25) months. Adequate treatment adherence was reported by 68.3% of patients. In addition, 73.6% of patients exhibited an adequate therapeutic response. The majority (82.6%) of patients who were treated with SMX-TMP for > 24 months displayed an adequate therapeutic response, and the frequency of adequate therapeutic response gradually decreased as the duration of treatment decreased. Treatment nonadherence (P < 0.001) and PCM-HIV coinfection (P = 0.019) were factors associated with therapeutic failure. The study results support the good efficacy of SMX-TMP. Attention should be given to PCM-HIV coinfection, emphasizing the concern of a higher risk of PCM therapeutic failure in these patients.

• • Pilot Intervention Study of Household Ventilation and Fine Particulate Matter Concentrations in a Low-Income Urban Area, Dhaka, Bangladesh

    Authors: Anne M. Weaver, Shahana Parveen, Doli Goswami, Christina Crabtree-Ide, Carole Rudra, Jihnhee Yu, Lina Mu, Alicia M. Fry, Iffat Sharmin, Stephen P. Luby and Pavani K. Ram

    Available online: 30 May 2017

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    Fine particulate matter (PM2.5) is a risk factor for pneumonia; ventilation may be protective. We tested behavioral and structural ventilation interventions on indoor PM2.5 in Dhaka, Bangladesh. We recruited 59 good ventilation (window or door in ≥ 3 walls) and 29 poor ventilation (no window, one door) homes. We monitored baseline indoor and outdoor PM2.5 for 48 hours. We asked all participants to increase ventilation behavior, including opening windows and doors, and operating fans. Where permitted, we installed windows in nine poor ventilation homes, then repeated PM2.5 monitoring. We estimated effects using linear mixed-effects models and conducted qualitative interviews regarding motivators and barriers to ventilation. Compared with poor ventilation homes, good ventilation homes were larger, their residents wealthier and less likely to use biomass fuel. In multivariable linear mixed-effects models, ventilation structures and opening a door or window were inversely associated with the number of hours PM2.5 concentrations exceeded 100 and 250 μg/m3. Outdoor air pollution was positively associated with the number of hours PM2.5 concentrations exceeded 100 and 250 μg/m3. Few homes accepted window installation, due to landlord refusal and fear of theft. Motivators for ventilation behavior included cooling of the home and sunlight; barriers included rain, outdoor odors or noise, theft risk, mosquito entry, and, for fan use, perceptions of wasting electricity or unavailability of electricity. We concluded that ventilation may reduce indoor PM2.5 concentrations but, there are barriers to increasing ventilation and, in areas with high ambient PM2.5 concentrations, indoor concentrations may remain above recommended levels.

• • Household and Individual Risk Factors for Cholera among Cholera Vaccine Recipients in Rural Haiti

    Authors: Wilfredo R. Matias, Jessica E. Teng, Isabelle J. Hilaire, Jason B. Harris, Molly F. Franke and Louise C. Ivers

    Available online: 30 May 2017

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    Oral cholera vaccination was used as part of cholera control in Haiti, but the vaccine does not provide complete protection. We conducted secondary data analyses of a vaccine effectiveness study in Haiti to evaluate risk factors for cholera among cholera vaccine recipients. Individuals vaccinated against cholera that presented with acute watery diarrhea and had a stool sample positive for Vibrio cholerae O1 were included as cases. Up to four vaccinated individuals who did not present for treatment of diarrhea were included as controls for each case, and matched by location of residence, enrollment time, and age. We evaluated sociodemographic characteristics and risk factors for cholera. Univariable and multivariable logistic regression were performed to identify risk factors for cholera among vaccinees. Thirty-three vaccine recipients with culture-confirmed cholera were included as cases. One-hundred-and-seventeen of their matched controls reported receiving vaccine and were included as controls. In a multivariable analysis, self-reporting use of branded household water disinfection products as a means of treating water (adjusted relative risk [aRR] = 44.3, 95% confidence interval [CI] = 4.19–468.05, P = 0.002), and reporting having a latrine as the main household toilet (aRR = 4.22, 95% CI = 1.23–14.43, P = 0.02), were independent risk factors for cholera. Self-reporting always treating water (aRR = 0.09, 95% CI = 0.01–0.5, P = 0.01) was associated with protection against cholera. The field effectiveness of water, sanitation, and hygiene interventions used in combination with cholera vaccination in cholera control should be measured and monitored over time to identify and remediate shortcomings, and ensure successful impact on disease control.

• • Cystic Echinococcosis in Turkana, Kenya: The Role of Cross-Sectional Screening Surveys in Assessing the Prevalence of Human Infection

    Authors: Nadia Solomon, Eberhard Zeyhle, Jane Carter, John Wachira, Asrat Mengiste, Thomas Romig, Paul J. Fields and Calum N. L. Macpherson

    Available online: 30 May 2017

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    Cystic echinococcosis (CE) is a neglected zoonotic disease caused by Echinococcus granulosus. Infection leads to formation of cysts within the viscera of the human host. In the 1980s, the transhumant population of northwest Turkana, Kenya, was found to have the highest prevalence of CE in the world. In 1983, AMREF Health Africa and the Kenya Medical and Research Institute launched a CE Control Program in northwest Turkana, screening and treating the local people. This epidemiological study of CE in Turkana analyses approximately 30 years of surveillance and surgical data. Cyst data were categorized using the World Health Organization CE ultrasound classification system before being analyzed for cyst, patient, and population characteristics, and surveillance data from 1985 are compared with more recent surveillance data to assess changes in prevalence in the control region since the commencement of control activities. In 1985, the prevalence of CE among the Turkana was 5.6%. In 2010–2011 and 2011–2012, calculated CE prevalence rates were 1.9% and 3.8%, respectively. Since the 1980s, the age distribution of people with CE in Turkana has shifted: initially, cases of CE appeared predominantly within younger age groups, but recent data reveal a higher prevalence within older age groups. The frequency of infection in females also significantly decreased. The reduction in CE prevalence from 5.6% in the 1980s to 1.9–3.8% in 2010–2012 and the shift in age distribution of CE-infected individuals over time indicate that the prevalence of CE in Turkana has decreased since the control program began.

• • Active Tuberculosis Case Finding in Haiti

    Authors: Jack Masur, Serena P. Koenig, Pierrot Julma, Oksana Ocheretina, Maria A. Durán-Mendicuti, Daniel W. Fitzgerald and Jean W. Pape

    Available online: 30 May 2017

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    In 2010, Haiti suffered from a devastating earthquake; data on the impact on the tuberculosis (TB) epidemic are limited. From January to June 2013, we conducted active case finding at the household level in a slum in Port-au-Prince. Community health workers identified individuals with cough ≥ 2 weeks, and referred them for evaluation. Contact tracing was conducted for patients with active TB. Of an estimated 7,500 residents screened, 394 (5%) had cough and were tested for TB. One hundred (25%) were diagnosed with active TB; 53 (53%) were smear positive. Ninety of these TB index cases provided 317 contacts, and 44 (14%) were diagnosed with active TB; 17 (39%) were smear positive. Overall, 144 TB cases were detected in 6 months (1,920/100,000; national estimate 200/100,000). We found a high burden of undiagnosed TB in Port-au-Prince 3 years after the earthquake. Further assessment of the burden of TB is indicated.

• • Phase 2a, Open-Label, 4-Escalating-Dose, Randomized Multicenter Study Evaluating the Safety and Activity of Ferroquine (SSR97193) Plus Artesunate, versus Amodiaquine Plus Artesunate, in African Adult Men with Uncomplicated Plasmodium falciparum Malaria

    Authors: Christian Supan, Ghyslain Mombo-Ngoma, Maryvonne Kombila, Carmen L. Ospina Salazar, Jana Held, Bertrand Lell, Cathy Cantalloube, Elhadj Djeriou, Bernhards Ogutu, John Waitumbi, Nekoye Otsula, Duncan Apollo, Mark E. Polhemus, Peter G. Kremsner and Douglas S. Walsh

    Available online: 30 May 2017

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    Artemisinin-based combination therapies are recommended as first-line agents for treating uncomplicated Plasmodium falciparum malaria. Ferroquine, a 4-aminoquinolone, is a novel long-acting combination partner for fast-acting drugs like artesunate (AS). We did a small phase 2a, multicenter, open-label, safety-focused dose-ranging randomized study of ferroquine at three African hospitals: two Gabonese and one Kenyan. We recruited adult men with symptomatic uncomplicated P. falciparum monoinfection. Four escalating doses of ferroquine (100, 200, 400, and 600 mg) were assessed in sequence, versus an amodiaquine comparator. After a 2:1 randomization (block size three, equating to N = 12 for each ferroquine dose and N = 6 for each of four amodiaquine comparator groups) patients received daily for three consecutive days, either ferroquine + AS (200 mg/day) or amodiaquine (612 mg/day) + AS (200 mg/day). Safety, electrocardiograms, parasite clearance times, efficacy, and pharmacokinetics were assessed to day 28. Seventy-two patients were randomized. Ferroquine + AS showed generally mild increases (Grade 1 toxicity) in alanine aminotransferase (ALT) levels with a dose trend starting at 400 mg. There were two Grade 2 ALT events: one patient receiving 200 mg (3.8 upper limit of normal [ULN], day 7) and one receiving 600 mg (3.3 ULN, day 14), both without increased bilirubin. One ferroquine 100 mg + AS patient after one dose was withdrawn after developing a QTcF interval prolongation > 60 milliseconds over baseline. Parasitemias in all patients cleared quickly, with no recurrence through day 28. Hepatic, as well as cardiac, profiles should be monitored closely in future trials. (ClinicalTrials.gov: NCT00563914)

• • Molecular Epidemiology of Staphylococcus aureus Skin and Soft Tissue Infections in the Lao People’s Democratic Republic

    Authors: Alicia D. Yeap, Kate Woods, David A. B. Dance, Bruno Pichon, Sayaphet Rattanavong, Viengmon Davong, Rattanaphone Phetsouvanh, Paul N. Newton, Nandini Shetty and Angela M. Kearns

    Available online: 30 May 2017

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    This is the first report of the molecular epidemiology of Staphylococcus aureus from skin and soft tissue infections (SSTI) in Laos. We selected a random sample of 96 S. aureus SSTI isolates received by the Microbiology Laboratory, Mahosot Hospital, Vientiane, between July 2012 and June 2014, including representation from seven referral hospitals. Isolates underwent susceptibility testing by Clinical and Laboratory Standards Institute methods, spa typing and DNA microarray analysis, with whole genome sequencing for rare lineages. Median patient age was 19.5 years (interquartile range 2–48.5 years); 52% (50) were female. Forty-three spa types, representing 17 lineages, were identified. Fifty-eight percent (56) of all isolates encoded Panton-Valentine leukocidin (PVL), representing six lineages: half of these patients had abscesses and three had positive blood cultures. The dominant lineage was CC121 (39; 41%); all but one isolate encoded PVL and 49% (19) were from children under five. Staphyococcus argenteus was identified in six (6%) patients; mostly adults > 50 years and with diabetes. Six isolates (6%) belonged to rare lineage ST2885; two possibly indicate cross-infection in a neonatal unit. One isolate from a previously undescribed lineage, ST1541, was identified. Antibiotic resistance was uncommon except for penicillin (93; 97%) and tetracycline (48; 50%). Seven (7%) isolates were methicillin-resistant S. aureus (MRSA), belonging to ST239-MRSA-III, CC59-MRSA-V(T) Taiwan Clone, ST2250-MRSA-IV, ST2885-MRSA-V and CC398-MRSA-V. Globally widespread CC5 and CC30 were absent. There are parallels in S. aureus molecular epidemiology between Laos and neighboring countries and these data highlight the prominence of PVL and suggest infiltration of MRSA clones of epidemic potential from surrounding countries.

• • Infant Nutritional Status, Feeding Practices, Enteropathogen Exposure, Socioeconomic Status, and Illness Are Associated with Gut Barrier Function As Assessed by the Lactulose Mannitol Test in the MAL-ED Birth Cohort

    Authors: Gwenyth O. Lee, Benjamin J. J. McCormick, Jessica C. Seidman, Margaret N. Kosek, Rashidul Haque, Maribel Paredes Olortegui, Aldo A. M. Lima, Zulfiqar A. Bhutta, Gagandeep Kang, Amidou Samie, Caroline Amour, Carl J. Mason, Tahmeed Ahmed, Pablo Peñataro Yori, Domingos B. Oliveira, Didar Alam, Sudhir Babji, Pascal Bessong, Estomih Mduma, Sanjaya K. Shrestha, Ramya Ambikapathi, Dennis R. Lang, Michael Gottlieb, Richard L. Guerrant, Laura E. Caulfield and for the MAL-ED Network Investigators

    Available online: 30 May 2017

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    The lactulose mannitol (LM) dual sugar permeability test is the most commonly used test of environmental enteropathy in developing countries. However, there is a large but conflicting literature on its association with enteric infection and host nutritional status. We conducted a longitudinal cohort using a single field protocol and comparable laboratory procedures to examine intestinal permeability in multiple, geographically diverse pediatric populations. Using a previously published systematic review to guide the selection of factors potentially associated with LM test results, we examined the relationships between these factors and mucosal breach, represented by percent lactulose excretion; absorptive area, represented by percent mannitol excretion; and gut barrier function, represented by the L/M ratio. A total of 6,602 LM tests were conducted in 1,980 children at 3, 6, 9, and 15 months old; percent lactulose excretion, percent mannitol excretion, and the L/M ratio were expressed as age- and sex-specific normalized values using the Brazil cohort as the reference population. Among the factors considered, recent severe diarrhea, lower socioeconomic status, and recent asymptomatic enteropathogen infections were associated with decreased percent mannitol excretion and higher L/M ratios. Poorer concurrent weight-for-age, infection, and recent breastfeeding were associated with increased percent lactulose excretion and increased L/M ratios. Our results support previously reported associations between the L/M ratio and factors related to child nutritional status and enteropathogen exposure. These results were remarkably consistent across sites and support the hypothesis that the frequency of these exposures in communities living in poverty leads to alterations in gut barrier function.

• • Morphometric Wings Similarity among Sylvatic and Domestic Populations of Triatoma infestans (Hemiptera: Reduviidae) from the Gran Chaco Region of Paraguay

    Authors: Antonieta Rojas de Arias, Ana Laura Carbajal de la Fuente, Ana Gómez, María Carla Cecere, Miriam Rolón, María Celeste Vega Gómez and Cesia Villalba

    Available online: 30 May 2017

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    Despite sustained efforts for eliminating Triatoma infestans, reinfestation still persists in large part of the endemic area of Chagas disease from the Gran Chaco region. Sylvatic T. infestans populations seem to threat success of control programs of domestic T. infestans. In this study, we analyze whether T. infestans collected after a community-wide spraying were survivors or were immigrants from elsewhere using geometric morphometric tools. We used 101 right wings of female T. infestans captured before and after intervention program carried out in 12 de Junio and Casuarina, villages from Paraguayan Chaco, and in Puerto Casado during presprayed collection. There were no significant differences in wing size of domestic T. infestans between pre- and postspraying populations, and between domestic and sylvatic ones. When shape variables originating from postintervention individuals from 12 de Junio were introduced one by one into a discriminant analysis, the greatest weight (53%) was allocated to the sylvatic group. Furthermore, from the prespraying population, 25% were reallocated as postintervention individuals. Only 11% of the insects were reassigned to other groups Puerto Casado and Casuarina. These results suggest that postspraying individuals appear to have different origins. Half of the postspraying individuals from 12 de Junio were similar to the sylvatic ones and 25% of these were similar to those captured in the prespraying period. This remarkable morphometric wings similarity between sylvatic and domestic populations is new evidence suggesting that they could be highly related to each other in the Paraguayan Chaco; human-fed bugs from sylvatic area also support this.

• • Silencing of Two Vitellogenin Genes Inhibits Oviposition in the Chagas Disease Vector Triatoma infestans (Hemiptera: Reduviidae)

    Authors: María J. Blariza, Carla G. Grosso and Beatriz A. García

    Available online: 30 May 2017

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    RNA interference caused by exogenous double-stranded RNA (dsRNA) is used to downregulate crucial genes to control insects. The reproductive success of all oviparous species depends on vitellogenin (Vg) biosynthesis and its accumulation in the developing oocytes. Adult females of Triatoma infestans were independently injected with two Vg dsRNAs (Vg1 dsRNA or Vg2 dsRNA) or nuclease-free water (control) 24 hours before feeding, and a group of adult females not injected was also analyzed (control). Vg1 and Vg2 messenger RNA silencing was verified by reverse transcription quantitative polymerase chain reaction. The transcript levels of the Vg1 and Vg2 genes were significantly reduced after dsRNA treatment in fat body and ovary of T. infestans in relation to those detected in individuals injected with nuclease-free water and not injected (controls). Moreover, the present study demonstrated that the silencing of the Vg1 or Vg2 genes inhibits oviposition in the Chagas disease vector T. infestans. These findings may have important implications for the development of novel vector control strategies.

• • Schistosomiasis in European Travelers and Migrants: Analysis of 14 Years TropNet Surveillance Data

    Authors: Tilman Lingscheid, Florian Kurth, Jan Clerinx, Stefania Marocco, Begoña Trevino, Mirjam Schunk, José Muñoz, Ida E. Gjørup, Tomas Jelinek, Michel Develoux, Graham Fry, Thomas Jänisch, Matthias L. Schmid, Olivier Bouchaud, Sabino Puente, Lorenzo Zammarchi, Kristine Mørch, Anders Björkman, Heli Siikamäki, Andreas Neumayr, Henrik Nielsen, Urban Hellgren, Malgorzata Paul, Guido Calleri, Pavel Kosina, Bjørn Myrvang, José M. Ramos, Gudrun Just-Nübling, Anna Beltrame, José Saraiva da Cunha, Peter Kern, Laurence Rochat, August Stich, Peter Pongratz, Martin P. Grobusch, Norbert Suttorp, Martin Witzenrath, Christoph Hatz, Thomas Zoller and TropNet Schistosomiasis Investigator Group

    Available online: 30 May 2017

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    Schistosomiasis remains one of the most prevalent parasitic diseases worldwide and the infection is frequently found in travelers and migrants. The European Network for Tropical Medicine and Travel Health conducted a sentinel surveillance study on imported schistosomiasis between 1997 and 2010. This report summarizes epidemiological and clinical data from 1,465 cases of imported schistosomiasis. Direct pathogen detection and serology were the main diagnostic tools applied. Of these, 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants. Overall, only 18.6% of travelers had received pretravel advice; 95% of infections were acquired in the African region. On species level, Schistosoma mansoni was identified in 570 (39%) and Schistosoma haematobium in 318 (22%) cases; 57.5% of patients were symptomatic. Acute symptoms were reported in 27% of patients leading to earlier presentation within 3 months. Praziquantel was used in all patients to treat schistosomiasis. Many infections were detected in asymptomatic patients. In 47.4% of asymptomatic patients infection was detected by microscopy and in 39% by serology or antigen testing. Schistosomiasis remains a frequent infection in travelers and migrants to Europe. Travelers should be made aware of the risk of schistosomiasis infection when traveling to sub-Saharan Africa. Posttravel consultations particularly for returning expatriates are useful given the high potential for detecting asymptomatic infections.

• • A Direct from Blood Reverse Transcriptase Polymerase Chain Reaction Assay for Monitoring Falciparum Malaria Parasite Transmission in Elimination Settings

    Authors: Brian J. Taylor, Kjerstin Lanke, Shanna L. Banman, Isabelle Morlais, Merribeth J. Morin, Teun Bousema, Sanna R. Rijpma and Stephanie K. Yanow

    Available online: 30 May 2017

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    We describe a novel one-step reverse transcriptase real-time PCR (direct RT-PCR) for Plasmodium falciparum malaria parasites that amplifies RNA targets directly from blood. We developed the assay to identify gametocyte-specific transcripts in parasites from patient blood samples, as a means of monitoring malaria parasite transmission in field settings. To perform the test, blood is added directly to a master mix in PCR tubes and analyzed by real-time PCR. The limit of detection of the assay on both conventional and portable real-time PCR instruments was 100 parasites/mL for 18S rRNA, and 1,000 parasites/mL for asexual (PFE0065W) and gametocyte (PF14_0367, PFGEXP5) mRNA targets. The usefulness of this assay in field studies was explored in samples from individuals living in a high-transmission region in Cameroon. The sensitivity and specificity of the assay compared with a standard two-step RT-PCR was 100% for 18S rRNA on both conventional and portable instruments. For PF14_0367, the sensitivity and specificity were 85.7% and 70.0%, respectively, on the conventional instrument and 78.6% and 90%, respectively, on the portable instrument. The concordance for assays run on the two instruments was 100% for 18S rRNA, and 79.2% for PF14_0367, with most discrepancies resulting from samples with low transcript levels. The results show asexual and sexual stage RNA targets can be detected directly from blood samples in a simple one-step test on a field-friendly instrument. This assay may be useful for monitoring malaria parasite transmission potential in elimination settings, where sensitive diagnostics are needed to evaluate the progress of malaria eradication initiatives.

• • A Cluster of Symptomatic and Asymptomatic Infections of Severe Fever with Thrombocytopenia Syndrome Caused by Person-to-Person Transmission

    Authors: Deyu Huang, Yueping Jiang, Xiaoping Liu, Bo Wang, Junming Shi, Zhan Su, Hui Wang, Ting Wang, Shuang Tang, Hanyun Liu, Zhihong Hu, Fei Deng and Shu Shen

    Available online: 30 May 2017

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    Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus that was identified to be the etiological pathogen of the emerging infectious disease, severe fever with thrombocytopenia syndrome (SFTS). SFTSV could be transmitted through tick bite. Transmission of SFTSV among humans has also been reported mainly through direct blood contact. In July 2014, a cluster of six suspected SFTS cases occurred in Shandong Province, China. In this cluster, both symptomatic and asymptomatic persons were included. By analyzing the clinical data and results of laboratory tests, and conducting the epidemiological interviews with the cases and their families, risk factors responsible for the transmission were evaluated. The findings suggested that SFTSV transmission among humans may cause asymptomatic infection via personal contact without blood exposure.

• • The Use of Xenosurveillance to Detect Human Bacteria, Parasites, and Viruses in Mosquito Bloodmeals

    Authors: Joseph R. Fauver, Alex Gendernalik, James Weger-Lucarelli, Nathan D. Grubaugh, Doug E. Brackney, Brian D. Foy and Gregory D. Ebel

    Available online: 30 May 2017

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    Infectious disease surveillance is hindered by several factors, including limited infrastructure and geographic isolation of many resource-poor regions. In addition, the complexities of sample acquisition, processing, and analysis, even in developed regions, can be rate limiting. Therefore, new strategies to survey human populations for emerging pathogens are necessary. Xenosurveillance is a method that utilizes mosquitoes as sampling devices to search for genetic signatures of pathogens in vertebrates. Previously we demonstrated that xenosurveillance can detect viral RNA in both laboratory and field settings. However, its ability to detect bacteria and parasites remains to be assessed. Accordingly, we fed Anopheles gambiae mosquitoes blood that contained Trypanosoma brucei gambiense and Bacillus anthracis. In addition, we determined whether two additional emerging viruses, Middle East Respiratory Syndrome Coronavirus and Zika virus could be detected by this method. Pathogen-specific real-time reverse transcription polymerase chain reaction was used to evaluate the sensitivity of xenosurveillance across multiple pathogen taxa and over time. We detected RNA from all pathogens at clinically relevant concentrations from mosquitoes processed up to 1 day postbloodfeeding. These results demonstrate that xenosurveillance may be used as a tool to expand surveillance for viral, parasitic, and bacterial pathogens in resource-limited areas.

• • Case Report: Infectious Diseases in Pilgrims Visiting the Holy Land

    Authors: Orna Nitzan, Arnon Blum, Esther Marva, Adina Katz, Bat-Sheva Tzadok, Yaarit Nachum-Biala, Gad Baneth and Avi Peretz

    Available online: 30 May 2017

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    Every year Christian pilgrims from around the world visit the holy sites located around the Sea of Galilee. Some become ill during their stay with infectious diseases that were acquired in their country of origin, and are hospitalized at Poriya Medical Center. They pose a diagnostic challenge due to language barriers, the rarity of these infections in Israel, and the fact that diagnostic tests are not readily available. All patient records from 2015 of Holy Land tourists hospitalized at Poriya Medical Center were screened for the diagnosis of imported zoonotic diseases that are not commonly diagnosed in Israel. Three patients who were on a Holy Land tour were hospitalized during 2015 with laboratory-confirmed diagnostically challenging zoonotic infectious diseases: a 91-year-old priest from Ethiopia diagnosed with relapsing fever due to Borrelia recurrentis, an 85-year-old retired mountaineer from New Hampshire diagnosed with human granulocytic anaplasmosis, and a 57-year-old farmer from central Brazil diagnosed with leptospirosis. These case reports emphasize the importance of considering imported zoonotic infectious diseases and obtaining appropriate diagnostic tests when treating Holy Land travelers to Israel.

• • Serologic Evidence of Various Arboviruses Detected in White-Tailed Deer (Odocoileus virginianus) in the United States

    Authors: Kerri Pedersen, Eryu Wang, Scott C. Weaver, Paul C. Wolf, Adam R. Randall, Kyle R. Van Why, Amelia P.A. Travassos Da Rosa and Thomas Gidlewski

    Available online: 30 May 2017

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    White-tailed deer (Odocoileus virginianus) are an abundant mammal with a wide geographic distribution in the United States, which make them good sentinels for monitoring arboviral activity across the country. Exposure to various arboviruses has been detected in white-tailed deer, typically in conjunction with another diagnostic finding. To better assess the exposure of white-tailed deer to seven arboviruses, we tested 1,508 sera collected from 2010 to 2016 for antibodies to eastern equine encephalitis (2.5%), Powassan (4.2%), St. Louis encephalitis, (3.7%), West Nile (6.0%), Maguari (19.4%), La Crosse (30.3%), and bluetongue (7.8%) viruses. At least one arbovirus was detected in 51.3%, and exposure to more than one arbovirus was identified in 17.6% of the white-tailed deer sampled.

• • Malaria Infection and Gametocyte Carriage Rates in Preparation for Transmission Blocking Vaccine Trials in Bancoumana, Mali

    Authors: Mahamadoun Hamady Assadou, Issaka Sagara, Sara A. Healy, Merepen Agnes Guindo, Mamady Kone, Sintry Sanogo, M'Bouye Doucoure, Sekouba Keita, Ruth D. Ellis, Yimin Wu, Freda Omaswa, Patrick E. Duffy and Ogobara K. Doumbo

    Available online: 22 May 2017

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    The epidemiological characterization of transmission reservoirs is a critical step in preparation for interventional trials for malaria elimination/eradication. Using cluster sampling and households/compounds as units of sampling, we recruited and followed monthly, from June 2011 to June 2012, 250 volunteers 3 months to 50 years of age in Bancoumana, Mali. In July 2012, only participants 5–35 years of age (N = 121) were reenrolled and followed for an additional year. Malaria infection prevalence was highest in October in both 2011 (21.5%, 50/233) and 2012 (38.2%, 26/68). During both years, malaria infection prevalence was highest in children 5–14 years of age (P = 0.01 and P = 0.02, respectively). The gametocyte carriage prevalence was highest in November 2011 (7.6%, 17/225) and in October 2012 (16.2%, 11/68). Gametocyte carriage rates by age did not significantly differ in 2011 and 2012. In Bancoumana, the asexual and sexual parasite carriage rates are relatively high and highly seasonal. Seasonal variation and age differences in parasite and gametocyte carriage provide essential knowledge for the design of transmission blocking assay and vaccine studies in the field.

• • High Prevalence of Anemia but Low Level of Iron Deficiency in Preschool Children during a Low Transmission Period of Malaria in Rural Kivu, Democratic Republic of the Congo

    Authors: Esto Bahizire, Paluku Bahwere, Philippe Donnen, P. Lundimu Tugirimana, Serge Balol'ebwami, Michèle Dramaix, Chouchou Nfundiko, Raphaël Chirimwami and Kanigula Mubagwa

    Available online: 22 May 2017

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    Anemia is a worldwide public health concern especially in preschool children in developing countries and iron deficiency (ID) is generally assumed to cause at least 50% of the cases. However, data on this contribution are scarce. To close this gap, we determined in 2013 the contribution of ID in the etiology of anemia and measured others factors associated to noniron deficiency anemia (NIDA) in 900 preschool children randomly selected during a two-stage cluster nutritional survey in the Miti-Murhesa health zone, in eastern Democratic Republic of the Congo. In these children, we collected sociodemographic, clinical, and biological parameters and determined the nutritional status according to the World Health Organization 2006 standards. Anemia was defined as altitude-adjusted hemoglobin < 110 g/L and ID was defined as serum ferritin < 12 μg/L or < 30 μg/L in the absence or presence of inflammation, respectively. Median (interquartile range) age was 29.4 (12–45) months. The prevalence of anemia was 46.6% (391/838) among whom only 16.5% (62/377) had ID. Among children without signs of inflammation, only 4.4% (11/251) met the ferritin-based (unadjusted) definition of ID. Logistic regression analysis identified ID, history of fever during the last 2 weeks and mid-upper arm circumference < 125 mm as the only independent factors associated to anemia. In conclusion, anemia is a severe public health problem in the Miti-Murhesa health zone, but NIDA is mostly predominant and needs to be further studied. Control of infections and prevention of acute undernutrition (wasting) are some of appropriate interventions to reduce the burden anemia in this region.

• • Sustained High Cure Rate of Artemether–Lumefantrine Against Uncomplicated Plasmodium falciparum Malaria After 8 Years of Its Wide-Scale Use in Bagamoyo District, Tanzania

    Authors: Richard Mwaiswelo, Billy Ngasala, J. Pedro Gil, Maja Malmberg, Irina Jovel, Weiping Xu, Zul Premji, Bruno P. Mmbando, Anders Björkman and Andreas Mårtensson

    Available online: 15 May 2017

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    We assessed the temporal trend of artemether–lumefantrine (AL) cure rate after 8 years of its wide-scale use for treatment of uncomplicated Plasmodium falciparum malaria from 2006 to 2014 in Bagamoyo district, Tanzania. Trend analysis was performed for four studies conducted in 2006, 2007–2008, 2012–2013, and 2014. Patients with acute uncomplicated P. falciparum malaria were enrolled, treated with standard AL regimen and followed-up for 3 (2006), 28 (2014), 42 (2012–2013), or 56 (2007–2008) days for clinical and laboratory evaluation. Primary outcome was day 28 polymerase chain reaction (PCR)-adjusted cure rate across years from 2007 to 2014. Parasite clearance was slower for the 2006 and 2007–2008 cohorts with less than 50% of patients cleared of parasitemia on day 1, but was rapid for the 2012–2013 and 2014 cohorts. Day 28 PCR-adjusted cure rate was 168/170 (98.8%) (95% confidence interval [CI], 97.2–100), 122/127 (96.1%) (95% CI, 92.6–99.5), and 206/207 (99.5%) (95% CI, 98.6–100) in 2007–2008, 2012–2013, and 2014, respectively. There was no significant change in the trend of cure rate between 2007 and 2014 (χ2-trend test = 0.06, P = 0.90). Pretreatment P. falciparum multidrug-resistant gene 1 (Pfmdr1) N86 prevalence increased significantly across years from 13/48 (27.1%) in 2006 to 183/213 (85.9%) in 2014 (P < 0.001), and P. falciparum chloroquine resistance transporter gene (Pfcrt) K76 prevalence increased significantly from 24/47 (51.1%) in 2006 to 198/205 (96.6%) in 2014 (P < 0.001). The AL cure rate remained high after 8 years of its wide-scale use in Bagamoyo district for the treatment of uncomplicated P. falciparum malaria despite an increase in prevalence of pretreatment Pfmdr1 N86 and Pfcrt K76 between 2006 and 2014.

• • A Systematic Review and Meta-Analysis of Practices Exposing Humans to Avian Influenza Viruses, Their Prevalence, and Rationale

    Authors: Guillaume Fournié, Erling Høg, Tony Barnett, Dirk U. Pfeiffer and Punam Mangtani

    Available online: 15 May 2017

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    Almost all human infections by avian influenza viruses (AIVs) are transmitted from poultry. A systematic review was conducted to identify practices associated with human infections, their prevalence, and rationale. Observational studies were identified through database searches. Meta-analysis produced combined odds ratio estimates. The prevalence of practices and rationales for their adoptions were reported. Of the 48,217 records initially identified, 65 articles were included. Direct and indirect exposures to poultry were associated with infection for all investigated viral subtypes and settings. For the most frequently reported practices, association with infection seemed stronger in markets than households, for sick and dead than healthy poultry, and for H7N9 than H5N1. Practices were often described in general terms and their frequency and intensity of contact were not provided. The prevalence of practices was highly variable across studies, and no studies comprehensively explored reasons behind the adoption of practices. Combining epidemiological and targeted anthropological studies would increase the spectrum and detail of practices that could be investigated and should aim to provide insights into the rationale(s) for their existence. A better understanding of these rationales may help to design more realistic and acceptable preventive public health measures and messages.

• • Consistency of Use and Effectiveness of Household Water Treatment Among Indian Households Claiming to Treat Their Water

    Authors: Ghislaine Rosa and Thomas Clasen

    Available online: 08 May 2017

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    Household water treatment (HWT) can improve drinking water quality and prevent disease if used correctly and consistently by populations at risk. Current international monitoring estimates by the Joint Monitoring Program for water and sanitation suggest that at least 1.1 billion people practice HWT. These estimates, however, are based on surveys that may overstate the level of consistent use and do not address microbial effectiveness. We sought to assess how HWT is practiced among households identified as HWT users according to these monitoring standards. After a baseline survey (urban: 189 households, rural: 210 households) to identify HWT users, 83 urban and 90 rural households were followed up for 6 weeks. Consistency of reported HWT practices was high in both urban (100%) and rural (93.3%) settings, as was availability of treated water (based on self-report) in all three sampling points (urban: 98.8%, rural: 76.0%). Nevertheless, only 13.7% of urban and 25.8% of rural households identified at baseline as users of adequate HWT had water free of thermotolerant coliforms at all three water sampling points. Our findings raise questions about the value of the data gathered through the international monitoring of HWT as predictors of water quality in the home, as well as questioning the ability of HWT, as actually practiced by vulnerable populations, to reduce exposure to waterborne diseases.

• • Clinical Usefulness of Real-Time Polymerase Chain Reaction for the Diagnosis of Vibrio vulnificus Infection Using Skin and Soft Tissues

    Authors: Jun-Young Lee, Seok Won Kim, Dong-Min Kim, Na Ra Yun, Choon-Mee Kim and Sang-Hong Lee

    Available online: 08 May 2017

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    Vibrio vulnificus is a halophilic gram-negative bacillus isolated in seawater, fish, and shellfish. Infection by V. vulnificus is the most severe food-borne infection reported in the United States of America. Here, we aimed to examine the clinical usefulness of polymerase chain reaction (PCR) using tissue specimens other than blood samples as a diagnostic tool for V. vulnificus infection. A retrospective study was conducted with patients who underwent real-time PCR of toxR in both blood and skin tissues, including serum, bullae, swab, and operation room specimens, between 2006 and 2009. The median V. vulnificus DNA load of 14 patients in real-time PCR analysis of serum at the time of admission was 638.5 copies/mL blood, which was within the interquartile range (IQR: 37–3,225). In contrast, the median value by real-time PCR using the first tissue specimen at the time of admission was 16,650 copies/mL tissue fluid (IQR: 4,419–832,500). This difference was statistically significant (P = 0.022). DNA copy numbers in tissues were less affected by short-term antibiotic administration than that in blood samples, and antibiotic administration increased the DNA copy number in some patients. We found, for the first time, that DNA copy numbers in tissues of patients infected by V. vulnificus were higher than those in blood samples. Additionally, skin lesions were more useful than blood samples as specimens for PCR analysis in patients administered antibiotics for V. vulnificus infection before admission.

• • Polymerase Chain Reaction Testing of Tick Bite Site Samples for the Diagnosis of Human Granulocytic Anaplasmosis

    Authors: Choon-Mee Kim, Seok W. Kim, Dong-Min Kim, Na-Ra Yoon, Piyush Jha, Sook J. Jang, Young-Joon Ahn, Donghoon Lim, Seung H. Lee, Seon do Hwang and Yeong S. Lee

    Available online: 08 May 2017

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    Human granulocytic anaplasmosis (HGA) is a tick-borne infectious disease caused by Anaplasma phagocytophilum, an obligate intracellular bacterium. Until now, the utility of tick-bite site samples for HGA diagnosis has not been reported. Using a patient's buffy coat and tick-bite site crust samples, we performed polymerase chain reaction (PCR) testing using Ehrlichia- or Anaplasma-specific primers. PCR with buffy coat and crust samples obtained before doxycycline administration was positive. Six days after doxycycline administration, PCR with the buffy coat sample was negative but PCR with a crust tissue sample from the tick-bite site remained positive. This is the first case to suggest that crust tissue at the tick-bite site may be useful for early HGA diagnosis in patients who have already been treated with antibiotics such as doxycycline.

• • Zika Virus Meningoencephalitis and Myelitis and Associated Magnetic Resonance Imaging Findings

    Authors: Faruq Pradhan, Joseph D. Burns, Ahmed Agameya, Avignat Patel, Mohammad Alfaqih, Juan E. Small and Winnie Ooi

    Available online: 08 May 2017

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    Zika virus (ZIKV) has a wide clinical spectrum of associated neurologic disease including microcephaly and Guillain–Barre syndrome but, despite its known neurotropism, ZIKV meningoencephalitis and myelitis have been rare complications. We describe a case of ZIKV meningoencephalitis and probable myelitis and its associated magnetic resonance imaging findings that rapidly resolved during recovery in a previously healthy adult.

• • Hygienic Behaviors and Risks for Ascariasis Among College Students in Kabul, Afghanistan

    Authors: Mohammad Yousuf Mubarak, Abram L. Wagner, Bradley F. Carlson and Matthew L. Boulton

    Available online: 08 May 2017

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    Teenagers have a high prevalence of ascariasis in low-income countries with endemic disease, and their hygienic behaviors and access to proper sanitation may be limited in rapidly urbanizing settings. We studied university students in Kabul to estimate the proportion with ascariasis and determine the prevalence of risk factors for infection. Ascariasis was assessed through microscopy for 520 students attending Kabul Medical University. Overall, 15.8% of students were infected. Living in a hostel (21.2% versus 10.4% in houses) using well water (27.7% versus 9.7% for piped water), eating street food (29.4% versus 3.0% for those who do not), and eating unwashed vegetables (63.6% versus 8.8% for those who do not) were risk factors for infection. Recent city migrants who live in group hostels, including students, are important targets for interventions to reduce ascariasis. Such interventions could include encouraging individuals to prepare their own food and use only potable water.

• • Differential Vector Competency of Aedes albopictus Populations from the Americas for Zika Virus

    Authors: Sasha R. Azar, Christopher M. Roundy, Shannan L. Rossi, Jing H. Huang, Grace Leal, Ruimei Yun, Ildefonso Fernandez-Salas, Christopher J. Vitek, Igor A. D. Paploski, Pamela M. Stark, Jeremy Vela, Mustapha Debboun, Martin R. Nava, Uriel Kitron, Guilherme S. Ribeiro, Kathryn A. Hanley, Nikos Vasilakis and Scott C. Weaver

    Available online: 08 May 2017

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    To evaluate the potential role of Aedes albopictus (Skuse) as a vector of Zika virus (ZIKV), colonized mosquitoes of low generation number (≤ F5) from Brazil, Houston, and the Rio Grande Valley of Texas engorged on viremic mice infected with ZIKV strains originating from Senegal, Cambodia, Mexico, Brazil, or Puerto Rico. Vector competence was established by monitoring infection, dissemination, and transmission potential after 3, 7, and 14 days extrinsic incubation. Positive saliva samples were assayed for infectious titer. Although all three mosquito populations were susceptible to all ZIKV strains, rates of infection, dissemination, and transmission differed between mosquito and virus strains. Aedes albopictus from Salvador, Brazil, were the least efficient vectors; demonstrating susceptibility to infection to two American strains of ZIKV but failing to transmit virus in saliva. Mosquitoes from the Rio Grande Valley were the most efficient vectors and were capable of transmitting all three tested ZIKV strains into saliva after 14 days of extrinsic incubation. In particular, ZIKV strain DakAR 41525 (Senegal 1954) was significantly more efficient at dissemination and saliva deposition than the others tested in Rio Grande mosquitoes. Overall, our data indicate that, while Ae. albopictus is capable of transmitting ZIKV, its competence is potentially dependent on geographic origin of both the mosquito population and the viral strain.

• • Clinical Characteristics of Severe Japanese Encephalitis: A Case Series from South Korea

    Authors: Jun-Sang Sunwoo, Soon-Tae Lee, Keun-Hwa Jung, Kyung-Il Park, Jangsup Moon, Ki-Young Jung, Manho Kim, Sang Kun Lee and Kon Chu

    Available online: 08 May 2017

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    Japanese encephalitis (JE) virus is a major cause of devastating viral encephalitis, especially in Asia. Although a successful vaccination program led to its near-elimination over three decades in South Korea, the incidence of JE has increased since 2010. The present study investigated the clinical manifestations, laboratory findings, and factors affecting neurological outcomes of reemerging JE. We retrospectively reviewed medical records of laboratory-confirmed JE patients who presented with acute encephalitis syndrome at three tertiary hospitals between 2010 and 2015. A total of 17 patients with JE were identified. Their median age was 51 years, and 10 (58.5%) were men. The most common symptoms and signs were fever (94.1%), altered consciousness (94.1%), and headache (80.2%). Hyporeflexia (47.1%), seizures (35.2%), abnormal brainstem reflex (23.5%), and flaccid weakness (17.6%) were also noted. Brain imaging revealed thalamic lesions in all patients, with the hippocampus, midbrain, basal ganglia, and cerebral cortex affected to varying degrees. Sixteen patients (94.1%) required management in the intensive care unit with mechanical ventilation due to neurological deterioration. At the time of discharge, 11 (64.7%) had poor recovery, defined as Glasgow coma scale scores of less than 8, and remained ventilator dependent. Comparison between the two outcome groups indicated that midbrain involvement (P = 0.028) and rapid deterioration (P = 0.005) were associated with severe neurological sequelae. Given that JE is a vaccine-preventable disease, vaccination for adults should be considered in response to the reemergence of JE.

• • Prevention and Care of Hepatitis B in Senegal; Awareness and Attitudes of Medical Practitioners

    Authors: Antoine Jaquet, Gilles Wandeler, Judicaël Tine, Mouhamadou Baïla Diallo, Noel M. Manga, Ndeye Mery Dia, Fatou Fall, François Dabis and Moussa Seydi

    Available online: 08 May 2017

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    In highly endemic settings for hepatitis B virus (HBV) infection such as Senegal, access to HBV prevention and care is rapidly evolving. In this context, all medical practitioners should have baseline knowledge on HBV infection and promote access to vaccination, screening, and care. A knowledge and attitudes survey on HBV infection was conducted among a randomly selected sample of medical practitioners in Senegal. Participants were asked to fill-out a questionnaire on the HBV epidemiology, prevention, and treatment. A 60-item knowledge score was computed; the lower quartile of the observed score was used to define poor knowledge. Factors associated with poor knowledge were assessed using a logistic regression model. A total of 127 medical practitioners completed the questionnaire. Only 14 (11.0%) participants knew that HBV vaccine could be safely administered to pregnant women and 65 (51.2%) to newborns. Older practitioners (> 40 years) as well as general practitioners (compared with specialists) were more likely to have a poor knowledge score with odds ratios (ORs) of 3.1 (95% confidence interval [CI] 1.0–9.2) and 2.6 (95% CI 1.0–7.3), respectively. Practitioners who declared not to recommend HBV screening frequently during their consultation were more likely to present a poor knowledge score [OR: 3.0; (95% CI 1.1–8.2)]. As universal HBV screening is being promoted in countries with endemic HBV infection, our finding that poor screening attitudes were associated with a poor knowledge is of concern. There is a need to raise awareness of medical practitioners in Senegal toward universal HBV screening and early vaccination of newborns.

• • Clinical Features of a Case of Suspected Borrelia miyamotoi Disease in Hokkaido, Japan

    Authors: Kimiaki Yamano, Takuya Ito, Kaori Kiyanagi, Hirotaka Yamazaki, Mutsubu Sugawara, Takashige Saito, Norio Ohashi, Aya Zamoto-Niikura, Kozue Sato and Hiroki Kawabata

    Available online: 01 May 2017

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    We herein report a case of suspected Borrelia miyamotoi disease in Hokkaido, Japan. The patient complained of lassitude, arthralgia, and high fever after a tick bite. Furthermore, at the time of consultation, the patient exhibited momentary loss of consciousness and low blood pressure. Laboratory tests revealed elevation of liver enzymes, thrombocytopenia, and increased C-reactive protein. Seroconversion to B. miyamotoi glycerophosphoryl diester phosphodiesterase antigen suggested the patient was infected with a relapsing fever group Borrelia species.

• • Spatiotemporal Analysis of the Malaria Epidemic in Mainland China, 2004–2014

    Authors: Qiang Huang, Lin Hu, Qi-bin Liao, Jing Xia, Qian-ru Wang and Hong-Juan Peng

    Available online: 01 May 2017

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    The purpose of this study is to characterize spatiotemporal heterogeneities in malaria distribution at a provincial level and investigate the association between malaria incidence and climate factors from 2004 to 2014 in China to inform current malaria control efforts. National malaria incidence peaked (4.6/100,000) in 2006 and decreased to a very low level (0.21/100,000) in 2014, and the proportion of imported cases increased from 16.2% in 2004 to 98.2% in 2014. Statistical analyses of global and local spatial autocorrelations and purely spatial scan statistics revealed that malaria was localized in Hainan, Anhui, and Yunnan during 2004–2009 and then gradually shifted and clustered in Yunnan after 2010. Purely temporal clusters shortened to less than 5 months during 2012–2014. The two most likely clusters detected using spatiotemporal analysis occurred in Anhui between July 2005 and November 2007 and Yunnan between January 2010 and June 2012. Correlation coefficients for the association between malaria incidence and climate factors sharply decreased after 2010, and there were zero-month lag effects for climate factors during 2010–2014. Overall, the spatiotemporal distribution of malaria in China changed from relatively scattered (2004–2009) to relatively clustered (2010–2014). As the proportion of imported cases increased, the effect of climate factors on malaria incidence has gradually become weaker since 2011. Therefore, new warning systems should be applied to monitor resurgence and outbreaks of malaria in mainland China, and quarantine at borders should be reinforced to control the increasingly trend of imported malaria cases.

• • Severity of Pneumonia in Under 5-Year-Old Children from Developing Countries: A Multicenter, Prospective, Observational Study

    Authors: Thomas Bénet, Valentina Sanchez Picot, Shally Awasthi, Nitin Pandey, Ashish Bavdekar, Anand Kawade, Annick Robinson, Mala Rakoto-Andrianarivelo, Maryam Sylla, Souleymane Diallo, Graciela Russomando, Wilma Basualdo, Florence Komurian-Pradel, Hubert Endtz, Philippe Vanhems and Gláucia Paranhos-Baccalà

    Available online: 01 May 2017

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    Pneumonia is the leading cause of death in children. The objectives were to evaluate the microbiological agents linked with hypoxemia in hospitalized children with pneumonia from developing countries, to identify predictors of hypoxemia, and to characterize factors associated with in-hospital mortality. A multicenter, observational study was conducted in five hospitals, from India (Lucknow, Vadu), Madagascar (Antananarivo), Mali (Bamako), and Paraguay (San Lorenzo). Children aged 2–60 months with radiologically confirmed pneumonia were enrolled prospectively. Respiratory and whole blood specimens were collected, identifying viruses and bacteria by real-time multiplex polymerase chain reaction (PCR). Microbiological agents linked with hypoxemia at admission (oxygen saturation < 90%) were analyzed by multivariate logistic regression, and factors associated with 14-day in-hospital mortality were assessed by bivariate Cox regression. Overall, 405 pneumonia cases (3,338 hospitalization days) were analyzed; 13 patients died within 14 days of hospitalization. Hypoxemia prevalence was 17.3%. Detection of human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) in respiratory samples was independently associated with increased risk of hypoxemia (adjusted odds ratio [aOR] = 2.4, 95% confidence interval [95% CI] = 1.0–5.8 and aOR = 2.5, 95% CI = 1.1–5.3, respectively). Lower chest indrawing and cyanosis were predictive of hypoxemia (positive likelihood ratios = 2.3 and 2.4, respectively). Predictors of death were Streptococcus pneumoniae detection by blood PCR (crude hazard ratio [cHR] = 4.6, 95% CI = 1.5–14.0), procalcitonin ≥ 50 ng/mL (cHR = 22.4, 95% CI = 7.3–68.5) and hypoxemia (cHR = 4.8, 95% CI = 1.6–14.4). These findings were consistent on bivariate analysis. hMPV and RSV in respiratory samples were linked with hypoxemia, and S. pneumoniae in blood was associated with increased risk of death among hospitalized children with pneumonia in developing countries.

• • Performance of Real-Time Polymerase Chain Reaction Assays for the Detection of 20 Gastrointestinal Parasites in Clinical Samples from Senegal

    Authors: Doudou Sow, Philippe Parola, Khadime Sylla, Magatte Ndiaye, Pascal Delaunay, Philippe Halfon, Sabine Camiade, Thérèse Dieng, Roger C. K. Tine, Babacar Faye, Jean Louis Ndiaye, Yémou Dieng, Oumar Gaye, Didier Raoult and Fadi Bittar

    Available online: 01 May 2017

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    Gastrointestinal parasite infections represent one of the biggest public health problems in the world. Therefore, appropriate innovative tools are needed for assessing interventions to control these infections. This study aims to compare the performance of real-time polymerase chain reaction (PCR) assays to microscopic examination for detection of intestinal parasites. A direct microscopic examination and stool concentration was performed on 98 stool samples from patients attending Senegalese hospitals. Negative microscopic control samples were also collected in Nice and Marseille (France). Species-specific primers/probes were used to detect 20 common gastrointestinal protozoans and helminths. Positive frequency and the sensitivity of each real-time PCR assay were compared with conventional microscopic examination. Real-time PCR was positive in 72 of 98 samples (73.5%), whereas microscopic examination was positive in 37 (37.7%) samples (P < 0.001). The real-time PCR assays were more sensitive than microscopy, with 57.4% (31/54) versus 18.5% (10/54), respectively, in the detection of parasites in asymptomatic patients (P < 0.05). In terms of polyparasitism, there were more coinfections detected by real-time PCR assays compared with microscopic methods (25.5% versus 3.06%). In comparison to parasite prevalence on individual samples, the results showed a perfect agreement (100%) between the two techniques for seven species, whereas discrepancies were observed for the others (agreement percentage varying from 64.2% to 98.9%). Real-time PCR appeared to be superior to microscopic examination for the detection of parasites in stool samples. This assay will be useful in diagnostic laboratories and in the field for evaluating the efficacy of mass drug administration programs.

• • Phosphoproteome of Toxoplasma gondii–Infected Host Cells Reveals Specific Cellular Processes Predominating in Different Phases of Infection

    Authors: Cheng He, Ai-Yuan Chen, Hai-Xia Wei, Xiao-Shuang Feng and Hong-Juan Peng

    Available online: 01 May 2017

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    The invasion of Toxoplasma gondii tachyzoites into the host cell results in extensive host cell signaling activation/deactivation that is usually regulated by the phosphorylation/dephosphorylation. To elucidate how T. gondii regulates host cell signal transduction, the comparative phosphoproteome of stable isotope labeling with amino acids in cell culture–labeled human foreskin fibroblast cells was analyzed. The cells were grouped (Light [L], Medium [M], and Heavy [H] groups) based on the labeling isotope weight and were infected with T. gondii for different lengths of time (L: 0 hour; M: 2 hours; and H: 6 hours). A total of 892 phosphoproteins were identified with 1,872 phosphopeptides and 1,619 phosphorylation sites. The M versus L comparison revealed 694 significantly regulated phosphopeptides (436 upregulated and 258 downregulated). The H versus L comparison revealed 592 significantly regulated phosphopeptides (146 upregulated and 446 downregulated). The H versus M comparison revealed 794 significantly regulated phosphopeptides (149 upregulated and 645 downregulated). At 2 and 6 hours post-T. gondii infection, the most predominant host cell reactions were cell cycle regulation and cytoskeletal reorganization, which might be required for the efficient invasion and multiplication of T. gondii. Similar biological process profiles but different molecular function categories of host cells infected with T. gondii for 2 and 6 hours, which suggested that the host cell processes were not affected significantly by T. gondii infection but emphasized some differences in specific cellular processes at this two time points. Western blotting verification of some significantly regulated phosphoprotein phosphorylation sites was consistent with the mass spectra data. This study provided new insights into and further understanding of pathogen–host interactions from the host cell perspective.

• • Rickettsia australis and Queensland Tick Typhus: A Rickettsial Spotted Fever Group Infection in Australia

    Authors: Adam Stewart, Mark Armstrong, Stephen Graves and Krispin Hajkowicz

    Available online: 01 May 2017

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    Rickettsia australis, the etiologic agent of Queensland tick typhus (QTT), is increasingly being recognized as a cause of community-acquired acute febrile illness in eastern Australia. Changing human population demographics, climate change, and increased understanding of expanding vector distribution indicate QTT is an emerging public health threat. This review summarizes the epidemiology, pathogenesis, clinical features, treatment principles, and future directions of this disease. Increased recognition of QTT will enable consideration of and prompt treatment of R. australis infection by clinicians in Australia.

• • Seasonal Variation in the Epidemiology of Asymptomatic Plasmodium falciparum Infections Across Two Catchment Areas in Bongo District, Ghana

    Authors: Kathryn E. Tiedje, Abraham Oduro, Godfred Agongo, Thomas Anyorigiya, Daniel Azongo, Timothy Awine, Anita Ghansah, Mercedes Pascual, Kwadwo Koram and Karen P. Day

    Available online: 01 May 2017

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    Understanding the epidemiology of asymptomatic Plasmodium falciparum infections is critical for countries to move toward malaria elimination. Using different methods for parasite detection, we evaluated how seasonality, spatial location, and other factors affect the age-specific epidemiology of asymptomatic malaria in Bongo District, Ghana. Asymptomatic prevalence by microscopy decreased significantly from 42.5% at the end of the wet to 27.5% at the end of the dry season (P < 0.001). Using the 18S rRNA polymerase chain reactions (PCRs), all microscopy-negative samples were screened and prevalence of submicroscopic infections also decreased significantly from the wet (55.4%) to the dry (20.7%) season (P < 0.001). Combining detection methods, 74.4% and 42.5% of the population in the wet and dry seasons, respectively, had evidence of a P. falciparum infection. Interestingly in those > 20 years of age, we found evidence of infection in 64.3% of the population in the wet and 27.0% in the dry season. Using both microscopy and PCR, the asymptomatic P. falciparum reservoir peaks at the end of the wet season and infections in all age groups constitute the reservoir of malaria infection. At the end of the wet season, spatial heterogeneity in the prevalence and density of P. falciparum infections was observed between the two catchment areas surveyed in Bongo District. These results indicate that if elimination is to succeed, interventions will need to target not just P. falciparum infections in children but also in adults, and be implemented toward the end of the dry season in this area of west Africa.

• • Conventional Wisdom Versus Actual Outcomes: Challenges in the Conduct of an Ebola Vaccine Trial in Liberia During the International Public Health Emergency

    Authors: Gregg S. Larson, Beth R. Baseler, Marie L. Hoover, Jerome F. Pierson, Jemee K. Tegli, Melvin P. Johnson, Mark W. S. Kieh, Laura A. McNay and Wissedi Sio Njoh

    Available online: 01 May 2017

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    Clinical trials are challenging endeavors. Planning and implementing an investigational vaccine trial in Liberia, in the midst of an Ebola virus disease (EVD) epidemic that World Health Organization classified a public health emergency of international concern, presented extraordinary challenges. Normally, years of preparation and a litany of tasks lay the groundwork for a successful, randomized, blinded, placebo-controlled trial focused on safety and efficacy. Difficult research settings, unpredictable events, and other unique circumstances can add complexity. The setting in Liberia was especially problematic due to an infrastructure still badly damaged following a lengthy civil war and a very fragile health-care system that was further devastated by the EVD outbreak. The Partnership for Research on Vaccines in Liberia I EVD vaccine trial was planned and implemented in less than 3 months by a Liberian and U.S. research partnership, and its Phase II substudy was fully enrolled 3 months later. Contrasting conventional wisdom with trial outcomes offers an opportunity to compare early assumptions, barriers encountered, and adaptive strategies used, with end results. Understanding what was learned can inform future trial responses when disease outbreaks, especially in resource-poor locations with minimal infrastructure, pose a significant threat to public health.

• • Burden and Seasonality of Viral Acute Respiratory Tract Infections Among Outpatients in Southern Sri Lanka

    Authors: David Shapiro, Champica K. Bodinayake, Ajith Nagahawatte, Vasantha Devasiri, Ruvini Kurukulasooriya, Jeremy Hsiang, Bradley Nicholson, Aruna Dharshan De Silva, Truls Ostbye, Megan E. Reller, Christopher W. Woods and L. Gayani Tillekeratne

    Available online: 01 May 2017

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    In tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. We determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern Sri Lanka. From March 2013 to January 2015, we enrolled outpatients presenting with influenza-like illness (ILI). Nasal/nasopharyngeal samples were tested in duplicate using antigen-based rapid influenza testing and multiplex polymerase chain reaction (PCR) for respiratory viruses. Monthly proportion positive was calculated for each virus. Bivariable and multivariable logistic regression were used to identify associations between sociodemographic/clinical information and viral detection. Of 571 subjects, most (470, 82.3%) were ≥ 5 years of age and 53.1% were male. A respiratory virus was detected by PCR in 63.6% (N = 363). Common viral etiologies included influenza (223, 39%), human enterovirus/rhinovirus (HEV/HRV, 14.5%), respiratory syncytial virus (RSV, 4.2%), and human metapneumovirus (hMPV, 3.9%). Both ILI and influenza showed clear seasonal variation, with peaks from March to June each year. RSV and hMPV activity peaked from May to July, whereas HEV/HRV was seen year-round. Patients with respiratory viruses detected were more likely to report pain with breathing (odds ratio [OR] = 2.60, P = 0.003), anorexia (OR = 2.29, P < 0.001), and fatigue (OR = 2.00, P = 0.002) compared with patients with no respiratory viruses detected. ILI showed clear seasonal variation in southern Sri Lanka, with most activity during March to June; peak activity was largely due to influenza. Targeted infection prevention activities such as influenza vaccination in January–February may have a large public health impact in this region.

• • Knowledge and Prevention Practices Among U.S. Pregnant Immigrants from Zika Virus Outbreak Areas

    Authors: Abbey B. Berenson, Ha N. Trinh, Jacqueline M. Hirth, Fangjian Guo, Erika L. Fuchs and Scott C. Weaver

    Available online: 01 May 2017

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    We administered an anonymous survey to assess knowledge, attitudes, and prevention practices related to the Zika virus among pregnant women residing in Texas. Multivariate logistic regression models controlling for age, race/ethnicity, education, and number of years in the United States assessed differences between women born in outbreak areas (N = 390) versus those born in the United States (N = 249). Results demonstrated that most women wanted more information on the Zika virus and desired to obtain it from their physician. The majority did not know that the Zika virus could be spread through sex with an asymptomatic partner or how often those infected were symptomatic. Few women took precautions to avoid mosquito bites. Only 40% reported frequently using repellent; 21% stated that cost was problematic and almost half were concerned about use during pregnancy. Three-fourths stated they would agree to vaccination, if available. Compared with U.S.-born women, those born in outbreak areas were more likely to have already discussed the Zika virus with their doctor (adjusted odds ratio [aOR] = 1.86, 95% confidence interval [CI] = 1.27, 2.71) and identify microcephaly as the most common birth defect (aOR = 2.59, 95% CI = 1.78, 3.76). Moreover, women born in outbreak areas were less likely to desire to keep it a secret if they became infected (aOR = 0.47, 95% CI = 0.31, 0.71). This study found that, regardless of birthplace, pregnant women need more education on the Zika virus disease and assurance regarding the safety of using repellent during pregnancy. They also need financial assistance for repellent, especially if living in states where transmission by mosquitos has been reported.

• • Rift Valley Fever Seroprevalence in Coastal Kenya

    Authors: Elysse N. Grossi-Soyster, Tamara Banda, Crystal Y. Teng, Eric M. Muchiri, Peter L. Mungai, Francis M. Mutuku, Ginny Gildengorin, Uriel Kitron, Charles H. King and A. Desiree Labeaud

    Available online: 01 May 2017

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    Rift Valley fever virus (RVFV) causes severe disease in both animals and humans, resulting in significant economic and public health damages. The objective of this study was to measure RVFV seroprevalence in six coastal Kenyan villages between 2009 and 2011, and characterize individual-, household-, and community-level risk factors for prior RVFV exposure. Sera were tested for anti-RVFV IgG via enzyme-linked immunosorbent assay. Overall, 51 (1.8%; confidence interval [CI95] 1.3–2.3) of 2,871 samples were seropositive for RVFV. Seroprevalence differed significantly among villages, and was highest in Jego Village (18/300; 6.0%; CI95 3.6–9.3) and lowest in Magodzoni (0/248). Adults were more likely to be seropositive than children (P < 0.001). Seropositive subjects were less likely to own land or a motor vehicle (P < 0.01), suggesting exposure is associated with lower socioeconomic standing (P = 0.03). RVFV exposure appears to be low in coastal Kenya, although with some variability among villages.

• • Zika Virus Disease in the Americas: A Storm in the Making

    Authors: Carissa Etienne, Thais dos Santos and Marcos A. Espinal

    Available online: 01 May 2017

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    More than 700,000 cases of Zika virus (ZIKAV) disease have been officially reported to the Pan American Health Organization (PAHO) from 48 countries and territories of the Americas. The response led by the PAHO and partners suggests major lessons of this outbreak. A seemingly innocuous pathogen became the new villain, causing fear, economic losses and, most importantly, debilitating birth defects and neurological problems, reaffirming the well-known war principle of never to underestimate one's opponent. The ZIKAV tested public health capacities under the International Health Regulations, highlighting the need for continued investment in health security. Last but not least, the lack of appropriate tools was another reminder of the pressing need for innovative solutions to persistent problems. Latin America and the Caribbean have approximately 500 million persons living in areas at risk for transmission of ZIKAV. The fight against ZIKAV is not a 100-m race, but rather a marathon in which science and public health need to work hand in hand for the benefit of our peoples.

• • A Symptomatic Case of Hymenolepis diminuta Infection in an Urban-Dwelling Adult in Malaysia

    Authors: Arine Fadzlun Ahmad, Romano Ngui, Jaxinthe Ong, Farikha Sarip, Wan Hafiz Wan Ismail, Hasidah Omar, Zurainee Mohamed Nor, Amirah Amir, Yvonne A. L. Lim and Rohela Mahmud

    Available online: 24 April 2017

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    A case of Hymenolepis diminuta infection in a 43-year-old Malaysian male with persistent abdominal colicky pain is reported. Endoscopy revealed whitish worms in the lumen of the small intestine, which were identified as H. diminuta after microscopy. Patient was successfully treated with a single dose of praziquantel (25 mg/kg).

• • Analysis of Dengue Serotype 4 in Sri Lanka During the 2012–2013 Dengue Epidemic

    Authors: Anna Uehara, Hasitha Aravinda Tissera, Champica K. Bodinayake, Ananda Amarasinghe, Ajith Nagahawatte, L. Gayani Tillekeratne, Jie Cui, Megan E. Reller, Paba Palihawadana, Sunethra Gunasena, Aruna Dharshan Desilva, Annelies Wilder-Smith, Duane J. Gubler, Christopher W. Woods and October M. Sessions

    Available online: 24 April 2017

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    The four serotypes of dengue virus (DENV-1, -2, -3, and -4) have had a rapidly expanding geographic range and are now endemic in over 100 tropical and subtropical countries. Sri Lanka has experienced periodic dengue outbreaks since the 1960s, but since 1989 epidemics have become progressively larger and associated with more severe disease. The dominant virus in the 2012 epidemic was DENV-1, but DENV-4 infections were also commonly observed. DENV-4 transmission was first documented in Sri Lanka when it was isolated from a traveler in 1978, but has been comparatively uncommon since dengue surveillance began in the early 1980s. To better understand the molecular epidemiology of DENV-4 infections in Sri Lanka, we conducted whole-genome sequencing on dengue patient samples from two different geographic locations. Phylogenetic analysis indicates that all sequenced DENV-4 strains belong to genotype 1 and are most closely related to DENV-4 viruses previously found in Sri Lanka and those recently found to be circulating in India and Pakistan.

• • Experience with a Multinational, Secondary School Education Module with a Focus on Prevention of Virus Infections

    Authors: Laura Doornekamp, Karen M. Stegers-Jager, Odette M. Vlek, Tanja Klop, Marco Goeijenbier and Eric C. M. van Gorp

    Available online: 24 April 2017

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    Worldwide, virus infections are responsible for many diseases in terms of morbidity and mortality. Vaccinations and therapies are only available for relatively few virus infections and not always where they are needed. However, knowledge of transmission routes can prevent virus infection. In the context of this study, we measured the effects of a secondary school education module, named Viruskenner, on knowledge, attitude, and risk behavior as these relate to virus infections. A nonrandomized intervention study was conducted between April and August 2015 to assess the effect of this 2-month education module on knowledge, attitude, and behavior of 684 secondary school students in the Netherlands, Suriname, and Indonesia. For the Netherlands, a control group of a further 184 students was added. Factor analysis was performed on questions pertaining to attitude and behavior. Comparative analyses between pre- and posttest per country were done using multiple linear regression, independent sample T-tests, and one-way analysis of variance. These showed a significant increase in knowledge about virus infections and the prevention of infectious diseases among the Dutch and Surinamese groups, whereas a trend of increased knowledge was evident among the Indonesian participants. The Dutch control group showed an overall decrease in knowledge. Regression analyses showed that there was a significant interaction effect between participation and time on knowledge, attitude, and awareness and behavior and risk infection. Attitudes improved significantly in the intervention group. Pearson correlation coefficients between knowledge, attitude, and behavior were found to be positive.

• • Extensive Resistance of Anopheles sinensis to Insecticides in Malaria-Endemic Areas of Hainan Province, China

    Authors: Ding-wei Sun, Guang-ze Wang, Lin-hai Zeng, Shan-gan Li, Chang-hua He, Xi-min Hu and Shan-qing Wang

    Available online: 24 April 2017

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    Anopheles sinensis is one of the major malaria vectors and among the dominant species in Hainan Province, China. The resistance of An. sinensis to insecticides is an important threat to malaria control. However, few reports on insecticide resistance of An. sinensis were reported in this area. Eight districts in Hainan Province were selected as the study areas. Insecticide susceptibility bioassays were tested on wild-caught female mosquitoes of An. sinensis to 4% dichlorodiphenyltrichloroethane (DDT), 0.05% deltamethrin, and 5% malathion by using the World Health Organization standard resistance tube assay procedure. All the tested An. sinensis mosquitoes demonstrated resistance to 4% DDT, with less than 72% mortality in the standard assay. The populations from Baisha and Qiongzhong demonstrated possible resistance to 0.05% deltamethrin, with 94–95% mortality, whereas the populations from other districts demonstrated resistance to 0.05% deltamethrin in the standard assay. The populations from Baisha, Qiongzhong, and Dongfang demonstrated susceptibility but the populations from other districts demonstrated resistance. These results facilitate the improvement of effective control strategies for malaria vector mosquitoes in Hainan.

• • Regional Differences in the Prevalence of Major Opportunistic Infections Among Antiretroviral-Naïve Human Immunodeficiency Virus Patients in Japan, Northern Thailand, Northern Vietnam, and the Philippines

    Authors: Louie Mar A. Gangcuangco, Ikumi Sawada, Naho Tsuchiya, Cuong D. Do, Thanh Thuy T. Pham, Archawin Rojanawiwat, Marissa Alejandria, Katerina Leyritana, Yoshiyuki Yokomaku, Panita Pathipvanich and Koya Ariyoshi

    Available online: 24 April 2017

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    To identify regional differences in the distribution of opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in Asia, the medical records of antiretroviral therapy (ART)-naïve patients who attended the following tertiary hospitals from 2003 to 2011 were reviewed: Nagoya Medical Center (NMC, Nagoya, Japan), Lampang Hospital (LPH, Lampang, northern Thailand), Bach Mai Hospital (BMH, Hanoi, northern Vietnam), and Philippine General Hospital (PGH, Manila, Philippines). Logistic regression analyses were performed to identify associations between country of origin and risk of major OIs. In total, 1,505 patients were included: NMC, N = 365; LPH, N = 442; BMH, N = 384; and PGH, N = 314. The median age was 32 years, and 73.3% of all patients were male. The median CD4 count was 200 cells/μL. Most patients at NMC and PGH were men who have sex with men. Injection drug users were most common at BMH (35.7%). Mycobacterium tuberculosis (TB) was most common at PGH (N = 75) but was rare at NMC (N = 4). Pneumocystis pneumonia (PCP) prevalence was highest at NMC (N = 74) and lowest at BMH (N = 13). Multivariable logistic regression showed increased odds of TB at PGH (adjusted odds ratio [aOR] = 42.2, 95% confidence interval [CI] = 14.6–122.1), BMH (aOR = 12.6, CI = 3.9–40.3), and LPH (aOR = 6.6, CI = 2.1–21.1) but decreased odds of PCP at BMH (aOR = 0.1, CI = 0.04–0.2) and LPH (aOR = 0.2, CI = 0.1–0.4) compared with those at NMC. The cryptococcosis risk was increased at LPH (aOR = 6.2, CI = 0.9–41.0) compared with that at NMC. Cytomegalovirus (CMV) retinitis prevalences were similar in all countries. OI prevalence remained high among ART-naïve patients in our cohort. The risks of TB, PCP, and cryptococcosis, but not CMV retinitis, differed between countries. Improved early HIV detection is warranted.

• • Optimizing Household Chlorination Marketing Strategies: A Randomized Controlled Trial on the Effect of Price and Promotion on Adoption in Haiti

    Authors: Michael Ritter, Eveline Camille, Christophe Velcine, Rose-Kerline Guillaume and Daniele Lantagne

    Available online: 24 April 2017

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    Household water treatment can reduce diarrheal morbidity and mortality in developing countries, but adoption remains low and supply is often unreliable. To test effects of marketing strategies on consumers and suppliers, we randomized 1,798 households in rural Haiti and collected data on purchases of a household chlorination product for 4 months. Households received randomly selected prices ($0.11–$0.56 per chlorine bottle), and half received monthly visits from sales agents. Each $0.22 drop in price increased purchases by 0.10 bottles per household per month (P < 0.001). At the mean price, each 1% drop in price increased purchases by 0.45% (elasticity = 0.45). There is suggestive evidence that household visits by some sales agents increased purchases at mid-range prices; however, the additional revenue did not offset visit cost. Choosing the lowest price and conducting visits maximizes chlorine use, whereas slightly raising the retail price and not conducting visits maximizes cost recovery. For the equivalent cost, price discounts increase purchases 4.2 times as much as adding visits at the current retail price. In this context, price subsidies may be a more cost-effective use of resources than household visits, though all marketing strategies tested offer cost-effective ways to achieve incremental health impact. Decisions about pricing and promotion for health products in developing countries affect health impact, cost recovery, and cost-effectiveness, and tradeoffs between these goals should be made explicit in program design.

• • Susceptibility of Clinical Isolates of Burkholderia pseudomallei to a Lipid A Biosynthesis Inhibitor

    Authors: Sineenart Sengyee, Natnaree Saiprom, Suporn Paksanont, Direk Limmathurotsakul, Vanaporn Wuthiekanun and Narisara Chantratita

    Available online: 24 April 2017

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    Burkholderia pseudomallei is the causative agent of melioidosis, a serious infection associated with high mortality and relapse. Current antimicrobial therapy using ceftazidime (CAZ) is often ineffective. Inhibitors of LpxC, the enzyme responsible for lipid A biosynthesis, have potential antimicrobial activity against several Gram-negative bacteria in vivo, but their activity against B. pseudomallei is unclear. Herein, we investigated the susceptibility of B. pseudomallei clinical isolates to LpxC-4, an LpxC inhibitor, and LpxC-4 in combination with CAZ. Time-kill assays for bactericidal activity were conducted for B. pseudomallei K96243, revealing growth inhibition and bactericidal effect at LpxC-4 concentrations of 2 μg/mL and 4 μg/mL, respectively. No significant synergistic effect was observed with the combination of LpxC-4 and CAZ. LpxC-4 susceptibility was tested on three groups of clinical isolates: 1) CAZ- and trimethoprim–sulfamethoxazole (SXT)–susceptible (N = 71), 2) CAZ-resistant (N = 14), and 3) SXT-resistant (N = 23) isolates, by broth microdilution. The minimum concentration of LpxC-4 required to inhibit the growth of 90% of organisms was 2 μg/mL for all isolates. The median minimum inhibitory concentration of both the CAZ/SXT-susceptible and CAZ-resistant groups was 1 μg/mL (interquartile range [IQR] = 1–2 μg/mL), compared with 2 μg/mL (IQR = 2–4 μg/mL) for the SXT-resistant group. Cell morphology was observed after drug exposure by immunofluorescent staining, and a change from rod-shaped to cell wall–defective spherical cells was observed in surviving bacteria. LpxC-4 is a potent bactericidal agent against B. pseudomallei and warrants further testing as a new antibiotic to treat melioidosis.

• • Molecular Markers for Sensitive Detection of Plasmodium falciparum Asexual Stage Parasites and Their Application in a Malaria Clinical Trial

    Authors: Fitsum G. Tadesse, Kjerstin Lanke, Issa Nebie, Jodie A. Schildkraut, Bronner P. Gonçalves, Alfred B. Tiono, Robert Sauerwein, Chris Drakeley, Teun Bousema and Sanna R. Rijpma

    Available online: 24 April 2017

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    Plasmodium falciparum parasite life stages respond differently to antimalarial drugs. Sensitive stage-specific molecular assays may help to examine parasite dynamics at microscopically detectable and submicroscopic parasite densities in epidemiological and clinical studies. In this study, we compared the performance of skeleton-binding protein 1 (SBP1), ring-infected erythrocyte surface antigen, Hyp8, ring-exported protein 1 (REX1), and PHISTb mRNA for detecting ring-stage trophozoite-specific transcripts using quantitative reverse transcriptase polymerase chain reaction. Markers were tested on tightly synchronized in vitro parasites and clinical trial samples alongside established markers of parasite density (18S DNA and rRNA) and gametocyte density (Pfs25 mRNA). SBP1 was the most sensitive marker but showed low-level expression in mature gametocytes. Novel markers REX1 and PHISTb showed lower sensitivity but higher specificity for ring-stage trophozoites. Using in vivo clinical trial samples from gametocyte-negative patients, we observed evidence of persisting trophozoite transcripts for at least 14 days postinitiation of treatment. It is currently not clear if these transcripts represent viable parasites that may have implications for clinical treatment outcome or transmission potential.

• • Bidirectional Exchange in Global Health: Moving Toward True Global Health Partnership

    Authors: Gitanjili Arora, Christiana Russ, Maneesh Batra, Sabrina Butteris, Jennifer Watts and Michael Pitt

    Available online: 24 April 2017

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    Although there has been rapid growth in global health educational experiences over the last two decades, the flow of learners remains overwhelmingly one directional; providers from high-resourced settings travel to limited-resourced environments to participate in clinical care, education, and/or research. Increasingly, there has been a call to promote parity in partnerships, including the development of bidirectional exchanges, where trainees from each institution travel to the partner's setting to learn from and teach each other. As global health educators and steering committee members of the Association of Pediatric Program Directors Global Health Pediatric Education Group, we endorse the belief that we must move away from merely sending learners to international partner sites and instead become true global health partners offering equitable educational experiences. In this article, we summarize the benefits, review common challenges, and highlight solutions to hosting and providing meaningful global health experiences for learners from limited-resourced partner institutions to academic health centers in the United States.

• • Experimental Infection with and Maintenance of Cell Fusing Agent Virus (Flavivirus) in Aedes aegypti

    Authors: Maria Angelica Contreras-Gutierrez, Hilda Guzman, Saravanan Thangamani, Nikos Vasilakis and Robert B. Tesh

    Available online: 24 April 2017

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    During the past two decades, there has been a dramatic increase in the recognition and characterization of novel insect-specific flaviviruses (ISFVs). Some of these agents are closely related to important mosquito-borne flavivirus pathogens. Results of experimental studies suggest that mosquitoes and mosquito cell cultures infected with some ISFVs are refractory to superinfection with related flavivirus pathogens; and it has been proposed that ISFVs potentially could be used to alter the vector competence of mosquitoes and reduce transmission of specific flavivirus pathogens, such as dengue, West Nile, or Zika viruses. In order for an ISFV to be used in such a control strategy, the virus would have to be vertically transmitted at a high rate in the target vector population to insure its continued maintenance. This study compared the vertical transmission rates of an ISFV, cell fusing agent virus (CFAV), in two Aedes aegypti colonies: one naturally infected with CFAV and the other experimentally infected but previously free of the virus. CFAV filial infection rates in progeny of female mosquitoes from both colonies were > 90% after two generations of selection, indicating the feasibility of introducing an ISFV into a mosquito population. This and other considerations for evaluating the feasibility of using ISFVs as an arbovirus control strategy are discussed.

• • Endemic Amebiasis in Australia: Implications for Residents, Travelers, and Clinicians

    Authors: Simon Smith, Gael E. Phillips, William J. H. McBride and Josh Hanson

    Available online: 24 April 2017

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    Entamoeba histolytica is considered endemic in Australia; however, cases are rare, occurring almost exclusively in high-risk individuals. We describe a series of locally acquired, complicated cases in low-risk individuals from Far North Queensland in whom the diagnosis was delayed. Amebiasis may pose a greater local threat than is currently recognized.

• • Cognitive Outcomes and Psychiatric Symptoms of Retinopathy-Positive Cerebral Malaria: Cohort Description and Baseline Results

    Authors: Rachel Brim, Sebastian Mboma, Margaret Semrud-Clikeman, Sam Kampondeni, Jed Magen, Terrie Taylor and John Langfitt

    Available online: 24 April 2017

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    Cerebral malaria (CM) is a common cause of death and disability among children in sub-Saharan Africa. Many prior studies of neuropsychiatric morbidity have been limited by a cross-sectional design or a short duration of follow-up. Most have included subjects who may have presented with coma due to a disease process other than CM. No studies have assessed the relationship between magnetic resonance imaging (MRI) findings and long-term outcomes. The cognitive outcomes and psychiatric symptoms of retinopathy-positive CM cohort is the first large (N = 221) prospectively recruited cohort of stringently defined cases of CM and hospital-based, age-matched, non-CM controls in whom cognitive and psychiatric outcomes are assessed with standardized measures annually for up to 5 years. We report baseline characteristics of the cohort and outcomes at 1 month. At enrollment, CM cases were more likely to come from families with fewer socioeconomic resources and to have health characteristics that increase risk for malaria. In children younger than 5 years, cases were delayed in motor, language, and social development by approximately 6 months, compared with controls. More significant delays occurred in those with MRI abnormalities at the 1-month follow-up visit. There were no differences between cases and controls in inhibitory self-control, nor in cognitive function in children ≥ 5 years of age. The latter finding may be related to the smaller sample size, case-control imbalance in socioeconomic status, or the use of cognitive and behavioral assessments that are less culturally appropriate to this population. Continued follow-up will help determine predictors of long-term outcomes.

• • Development of a Real-Time Reverse Transcription Polymerase Chain Reaction for O'nyong-nyong Virus and Evaluation with Clinical and Mosquito Specimens from Kenya

    Authors: Jesse Waggoner, Claire Jane Heath, Bryson Ndenga, Francis Mutuku, Malaya K. Sahoo, Alisha Mohamed-Hadley, John Vulule, Dunstan Mukoko, A. Desiree LaBeaud and Benjamin A. Pinsky

    Available online: 24 April 2017

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    O'nyong-nyong virus (ONNV), an alphavirus closely related to chikungunya virus (CHIKV), has been the documented cause of two large outbreaks in east Africa; however, little is known about the contribution of ONNV to cases of acute febrile illness during interepidemic periods. An ONNV real-time reverse transcription polymerase chain reaction (rRT-PCR) was developed and evaluated using clinical and mosquito pool samples. The ONNV rRT-PCR linear range extended from 8.0 to 2.0 log10 copies/μL, and the lower limit of 95% detection was 22.4 copies/μL. No cases of ONNV infection were identified in serum from 385 Kenyan children who presented with an acute febrile illness. Additionally, ONNV was not detected in 120 mosquito pools collected in coastal and western Kenya. The ONNV rRT-PCR demonstrated good analytical sensitivity when performed in monoplex or as a component of an ONNV–CHIKV duplex assay. This assay should provide a useful diagnostic for the detection of ONNV in surveillance studies.

• • Malaria-Related Hospitalizations in the United States, 2000–2014

    Authors: Diana Khuu, Mark L. Eberhard, Benjamin N. Bristow, Marjan Javanbakht, Lawrence R. Ash, Shira C. Shafir and Frank J. Sorvillo

    Available online: 24 April 2017

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    Few data are available on the burden of malaria hospitalization in the United States. Study of malaria using hospital-based data can better define the impact of malaria and help inform prevention efforts. U.S. malaria cases identified from hospitalization discharge records in the 2000–2014 Nationwide Inpatient Sample were examined. Frequencies and population rates were reported by demographics, infecting species, clinical, financial, institutional, geographic, and seasonal characteristics, and disparities were identified. Time trends in malaria cases were assessed using negative binomial regression. From 2000 to 2014, there were an estimated 22,029 malaria-related hospitalizations (4.88 per 1 million population) in the United States, including 182 in-hospital deaths and 4,823 severe malaria cases. The rate of malaria-related hospitalizations did not change significantly over the study period. The largest number of malaria-related hospitalizations occurred in August. Malaria-related hospitalizations occurred disproportionately among patients who were male, black, or 25–44 years of age. Plasmodium falciparum accounted for the majority of malaria-related hospitalizations. On average, malaria patients were hospitalized for 4.36 days with charges of $25,789. Patients with a malaria diagnosis were more often hospitalized in the Middle Atlantic and South Atlantic census divisions, urban teaching, private not-for-profit, and large-bed-size hospitals. Malaria imposes a substantial disease burden in the United States. Enhanced primary and secondary prevention measures, including strategies to increase the use of pretravel consultations and prompt diagnosis and treatment are needed.

• • Climate Influence on Emerging Risk Areas for Rift Valley Fever Epidemics in Tanzania

    Authors: Clement N. Mweya, Leonard E. G. Mboera and Sharadhuli I. Kimera

    Available online: 17 April 2017

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    Rift Valley Fever (RVF) is a climate-related arboviral infection of animals and humans. Climate is thought to represent a threat toward emerging risk areas for RVF epidemics globally. The objective of this study was to evaluate influence of climate on distribution of suitable breeding habitats for Culex pipiens complex, potential mosquito vector responsible for transmission and distribution of disease epidemics risk areas in Tanzania. We used ecological niche models to estimate potential distribution of disease risk areas based on vectors and disease co-occurrence data approach. Climatic variables for the current and future scenarios were used as model inputs. Changes in mosquito vectors' habitat suitability in relation to disease risk areas were estimated. We used partial receiver operating characteristic and the area under the curves approach to evaluate model predictive performance and significance. Habitat suitability for Cx. pipiens complex indicated broad-scale potential for change and shift in the distribution of the vectors and disease for both 2020 and 2050 climatic scenarios. Risk areas indicated more intensification in the areas surrounding Lake Victoria and northeastern part of the country through 2050 climate scenario. Models show higher probability of emerging risk areas spreading toward the western parts of Tanzania from northeastern areas and decrease in the southern part of the country. Results presented here identified sites for consideration to guide surveillance and control interventions to reduce risk of RVF disease epidemics in Tanzania. A collaborative approach is recommended to develop and adapt climate-related disease control and prevention strategies.

• • A Fatal Hantavirus Pulmonary Syndrome Misdiagnosed as Dengue: An Investigation Into the First Reported Case in Rio de Janeiro State, Brazil

    Authors: Renata Carvalho de Oliveira, Alexandro Guterres, Bernardo Rodrigues Teixeira, Jorlan Fernandes, João Marcos Penna Júnior, Reynaldo de Jesus Oliveira Júnior, Liana Strecht Pereira, João Bosco Júnior, Patrícia Soares Meneguete, Cristina Maria Giordano Dias, Cibele Rodrigues Bonvicino, Paulo Sérgio D'Andrea and Elba Regina Sampaio de Lemos

    Available online: 17 April 2017

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    We report the results of an investigation into a fatal case of hantavirus pulmonary syndrome (HPS) in Rio de Janeiro State, Brazil, where the disease had not been reported previous to 2015. Following the notification of an HPS case, serum samples were collected from the household members and work contacts of the HPS patient and tested for antibody to hantaviruses. Seroprevalence of 22% (10/45) was indicated for hantavirus out of 45 human samples tested. Blood and tissue samples were collected from 72 rodents during fieldwork to evaluate the prevalence of hantavirus infection, by using enzyme-linked immunosorbent assay IgG, and to characterize the rodent hantavirus reservoir(s), by reverse transcription polymerase chain reaction and sequencing. Antibody prevalence was 6.9%. The circulation of a single genotype, the Juquitiba hantavirus, carried by two rodent species, black-footed pigmy rice rat (Oligoryzomys nigripes) and cursor grass mouse (Akodon cursor), was shown by analysis of the nucleotide sequences of the S segment. Juquitiba hantavirus circulates in rodents of various species, but mainly in the black-footed pigmy rice rat. HPS is a newly recognized clinical entity in Rio de Janeiro State and should be considered in patients with febrile illness and acute respiratory distress.

• • Seroprevalence of Toxoplasma gondii Infection in Refugee and Migrant Pregnant Women Along the Thailand–Myanmar Border

    Authors: Bert J. D. van Enter, Yee-Ling Lau, Clare L. Ling, Wanitda Watthanaworawit, Yaowalark Sukthana, Wenn-Chyau Lee, François Nosten and Rose McGready

    Available online: 17 April 2017

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    Toxoplasma gondii primary infection in pregnancy is associated with poor obstetric outcomes. This study aimed to determine the seroprevalence of Toxoplasma infection in pregnant migrant and refugee women from Myanmar attending antenatal care in Thailand. A random selection of 199 residual blood samples from first antenatal screen in 2014–2015 was tested for Toxoplasma IgG and IgM antibodies. Seroprevalence of Toxoplasma infection was 31.7% (95% confidence interval = 25.6–38.4). Avidity testing in the three positive IgM cases indicated all were past infections. Multiparity (≥ 3 children) was significantly associated with higher Toxoplasma seropositivity rates. Seroprevalence of T. gondii infection in this pregnant population is similar to the only other report from Myanmar, and was significantly associated with multiparity. Toxoplasma infection is important in pregnant women. Nevertheless, in this marginalized population, this infection may be given less priority, due to resource constraints in providing the most basic components of safe motherhood programs.

• • Disseminated Talaromyces (Penicillium) marneffei and Mycobacterium tuberculosis Coinfection in a Japanese Patient with Acquired Immunodeficiency Syndrome

    Authors: Shuji Hatakeyama, Takeshi Yamashita, Toshiyaku Sakai and Katsuhiko Kamei

    Available online: 17 April 2017

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    Talaromyces marneffei is a dimorphic fungus endemic mainly in southeast and south Asia. It causes severe mycosis, usually in immunocompromised individuals, such as those with human immunodeficiency virus (HIV) infection. Concomitant infection with T. marneffei and other opportunistic pathogens is plausible because the majority of T. marneffei infections occur in patients with advanced HIV infection. Nonetheless, coinfection in the same site has rarely been reported, and poses a considerable diagnostic and therapeutic challenge. We report the case of an HIV-infected Japanese patient who had lived in Thailand for 6 years. The patient developed T. marneffei and Mycobacterium tuberculosis coinfection, and both pathogens were isolated from the same sites: a blood specimen and a lymph node aspirate. Clinicians should be aware of concomitant infection with T. marneffei and other pathogens in patients with advanced HIV disease who are living in or who have visited endemic areas.

• • Analysis of Clinical and Laboratory Alterations Related to Dengue Case Severity: Comparison Between Serotypes 2 and 4 in Brazil

    Authors: Nieli Rodrigues da Costa Faria, Victor Edgar Fiestas Solorzano, Luiz José de Souza, Rita Maria Ribeiro Nogueira, Fernanda de Bruycker-Nogueira, Thaís Chouin-Carneiro, Jaqueline Bastos Santos Simões, Monique da Rocha Queiroz Lima, Luzia Maria de Oliveira Pinto, Claire Fernandes Kubelka, Manoela Heringer, Elzinandes Leal de Azeredo and Flavia Barreto dos Santos

    Available online: 10 April 2017

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    The increase in severe dengue (SD) cases has caused great impact on public health and has concerned authorities of countries where the disease is endemic and epidemics reach high proportions. The recognition of progression signs of this severe disease during the initial febrile phase can be difficult, since the symptoms are often indistinguishable from other febrile diseases. The aim of this study was to evaluate the clinical manifestations and laboratory findings in patients from two dengue outbreaks and their association with the disease. The study was conducted in patients (n = 153) with signs and symptoms consistent with dengue occurred during two distinct epidemics, 2010 and 2013, in the city of Campos dos Goytacazes, Rio de Janeiro, Brazil. According to the 2009 World Health Organization criteria, patients were classified as dengue without warning signs ([DwoWS] 60.6%, 57/94), dengue with warning signs ([DwWS] 30.9%, 29/94), and SD (4.25%, 4/94). Patients with DwWS/SD presented lower platelet and leukocyte counts and higher transaminase levels when compared with the DwoWS ones. Interestingly, patients from the epidemic of 2010 caused by dengue virus 2 (DENV-2) had lower platelet counts than patients of the 2013 epidemic caused by DENV-4. Furthermore, plasma leakage, gastrointestinal bleeding, and pleural effusion, hallmarks for a more severe disease, were also more frequently observed in those cases. Although previous studies may have extensively reported the wide range of the clinical aspects of dengue, the characterization of DENV-4 is desirable considering the burden of the disease during epidemics, especially for the health units and hospitals performing patient's management.

• • Infective Endocarditis in French West Indies: A 13-Year Observational Study

    Authors: Elisabeth Fernandes, Claude Olive, Jocelyn Inamo, François Roques, André Cabié and Patrick Hochedez

    Available online: 10 April 2017

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    We conducted an observational study to describe the characteristics of infective endocarditis (IE) in French West Indies (FWI) and to identify variables associated with in-hospital case fatality. The records of the patients admitted for IE to the University Hospital of Martinique between 2000 and 2012 were collected using an electronic case report form. Only Duke-Li definite cases were considered for this analysis. Variables associated with in-hospital mortality were tested using univariate logistic regression analysis. The analysis included 201 patients (median age 58 years, sex ratio: two males to one female). There was no previously known heart disease in 45.8%, a prosthetic valve in 21.4%, and previously known native valve disease in 32.8% of the cases. Community-acquired IE represented 59.7% of all cases, health-care-associated IE represented 38.3% and injection-drug-use-acquired IE represented 1.5%. Locations of IE were distributed as follows: 42.3% were mitral valve IE, 34.8% were aortic valve IE, and 7% were right-sided IE. Microorganisms recovered from blood cultures included 30.4% streptococci, 28.9% staphylococci, and 5% enterococci. Blood cultures were negative in 20.9% of the cases. Surgical treatment was performed in 53% of the patients. In-hospital case fatality rate was 19%. Advanced age, Staphylococcus aureus IE, and health-care-associated IE were associated with in-hospital case fatality. The epidemiological and microbiological profile of IE in FWI is in between those observed in developed countries and developing countries: patients were younger, blood cultures were more frequently negative, and IE due to group D streptococci and enterococci were less common than in industrialized countries.

• • Serologic Monitoring of Public Health Interventions Against Strongyloides stercoralis

    Authors: Paola Vargas, Alejandro J. Krolewiecki, Adriana Echazú, Marisa Juarez, Pamela Cajal, Jose F. Gil, Nicolás Caro, Julio Nasser, Patrick Lammie and Rubén O. Cimino

    Available online: 10 April 2017

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    Northwestern Argentina is endemic for soil-transmitted helminths, and annual deworming programs are carried out in prioritized areas. High prevalence of Strongyloides stercoralis was reported in this area; therefore, control programs including ivermectin are being evaluated. The NIE-enzyme linked immunosorbent assay (ELISA) was used for this purpose. In this community trial, two groups of patients, classified according to housing and living conditions were evaluated. Simultaneous with baseline survey, Group 1 was moved to new households with access to improved water and sanitation facilities (W and S), where deworming (MDA, massive drug administration) took place within 1 month; whereas Group 2 received MDA but remained living with unimproved W and S. The mean time interval between baseline and the follow-up was 331 days for Group 1 and 508 for Group 2. Anti-NIE levels were measured for each individual before and after interventions and follow-up optical density (OD) ratios were calculated to quantify the variation. A significant decrease of the anti-NIE levels between baseline and follow-up was observed in both groups. Nonetheless, the number of patients that achieved the cure criteria (OD ratio < 0.6) was higher in Group 1 than Group 2 with values of 72.7% (24/33) and 45.0% (18/40), respectively (P = 0.0197). Our results support the conclusion that a combined intervention including deworming and improvements in life conditions is more effective, in terms of the proportion of subjects cured than deworming alone. Furthermore, we found that NIE-ELISA is a useful test for assessing the response to treatment and to evaluate the outcome of control intervention programs.

• • Factors Associated with the Duration of Moderate-to-Severe Diarrhea Among Children in Rural Western Kenya Enrolled in the Global Enteric Multicenter Study, 2008–2012

    Authors: Katharine A. Schilling, Richard Omore, Gordana Derado, Tracy Ayers, Ben J. Ochieng, Tamer H. Farag, Dilruba Nasrin, Sandra Panchalingam, James P. Nataro, Karen L. Kotloff, Myron M. Levine, Joseph Oundo, Michelle B. Parsons, Cheryl Bopp, Kayla Laserson, Christine E. Stauber, Richard Rothenberg, Robert F. Breiman, Ciara E. O'Reilly and Eric D. Mintz

    Available online: 10 April 2017

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    Diarrheal disease is a leading cause of death among young children worldwide. As rates of acute diarrhea (AD; 1–6 days duration) have decreased, persistent diarrhea (PD; > 14 days duration) accounts for a greater proportion of the diarrheal disease burden. We describe factors associated with the duration of moderate-to-severe diarrhea in Kenyan children < 5 years old enrolled in the Global Enteric Multicenter Study. We found 587 (58%) children experienced AD, 360 (35%) had prolonged acute diarrhea (ProAD; 7–13 days duration), and 73 (7%) had PD. We constructed a Cox proportional hazards model to identify factors associated with diarrheal duration. Risk factors independently associated with longer diarrheal duration included infection with Cryptosporidium (hazard ratio [HR]: 0.868, P = 0.035), using an unimproved drinking water source (HR: 0.87, P = 0.035), and being stunted at enrollment (HR: 0.026, P < 0.0001). Diarrheal illness of extended duration appears to be multifactorial; given its association with adverse health and development outcomes, effective strategies should be implemented to reduce the duration and severity of diarrheal illness. Effective treatments for Cryptosporidium should be identified, interventions to improve drinking water are imperative, and nutrition should be improved through exclusive breastfeeding in infants ≤ 6 months and appropriate continued feeding practices for ill children.

• • Association of Interferon-γ Receptor-1 Gene Polymorphism with Nontuberculous Mycobacterial Lung Infection Among Iranian Pulmonary Patients

    Authors: Poopak Farnia, Jalaledin Ghanavi, Shima Saif, Parissa Farnia and Ali Akbar Velayati

    Available online: 10 April 2017

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    Nontuberculous mycobacteria (NTM) cause significant pulmonary infections in humans. Researchers have reported an association between interferon-gamma receptor-1 (IFN-γR1 or IFNGR1) deficiency and susceptibility to NTM, but the relevance of polymorphism within these genes is not yet clear. In this study, a single nucleotide polymorphism (SNP), T to C, at position-56 in NTM pulmonary patients was investigated. Molecular identification of Mycobacterium isolates was performed with hsp65 genes using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Then, the host genomic DNA from confirmed NTM patients (N = 80) and control subjects (N = 80) were screened for SNPs of IFNGR1 (T-56C) by PCR-RFLP. The results indicated that NTM patients had higher TC (26/80; 32.5%) or CC (46/80; 57.5%) genotypes in comparison with control groups (TC genotypes [22/80, 27.5%]; CC genotypes [6/80, 7.5%]) (P < 0.05). In this regard, all the patients infected with rapid-growing Mycobacterium (RGM, i.e., Mycobacterium chelonae and Mycobacterium fortuitum) had CC genotypes (100%). In contrary, only 50.7% (35/69) of infected patients with slow-growing Mycobacterium (i.e., Mycobacterium simiae, Mycobacterium kansasii, and Mycobacterium avium-intracellulare) had CC genotypes. Thus, patients with CC mutation in IFNGR1 at position-56 are more likely to develop RGM infection. In overall, there is a significant association between SNP of IFNGR1 at position-56 and susceptibility to NTM infection. Based on these data, we propose SNP of IFNGR1 at position-56 as a suitable “biomarker” for identifying populations at higher risk of infection.

• • Chikungunya and Zika Virus Cases Detected Against a Backdrop of Endemic Dengue Transmission in Vietnam

    Authors: Nguyen Than Ha Quyen, Duong Thi Hue Kien, Maia Rabaa, Nguyen Minh Tuan, Tran Thuy Vi, Le Van Tan, Nguyen Thanh Hung, Ha Manh Tuan, Ta Van Tram, Nguyen Le Da Ha, Han Khoi Quang, Nguyen Quoc Doanh, Nguyen Van Vinh Chau, Bridget Wills and Cameron P. Simmons

    Available online: 10 April 2017

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    Between 2010 and 2014, four chikungunya and two Zika virus infections were identified among 8,105 febrile children in southern Vietnam. Zika viruses were linked to French Polynesian strains, chikungunya to Cambodian strains. Against a backdrop of endemic dengue transmission, chikungunya and Zika present an additional arboviral disease burden in Vietnam.

• • Microcephaly in Twins Due to the Zika Virus

    Authors: Victor S. Santos, Sheila J. G. Oliveira, Ricardo Q. Gurgel, Dorothy R. R. Lima, Cliomar A. dos Santos and Paulo R. S. Martins-Filho

    Available online: 10 April 2017

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    Recent studies have demonstrated an association between congenital Zika virus (ZIKV) infection and microcephaly; however, to date, there have been no reports on the consequences of ZIKV infection on fetuses in twin pregnancies. Herein, we reported on the first case of a monochorionic diamniotic (MCDA) twin pregnancy having ZIKV-related microcephaly. Our findings suggested that, in an MCDA twin pregnancy, the ZIKV may cause infection in both fetuses, resulting in severe abnormalities in the central nervous system due to neural cell destruction and the disruption of the normal development processes of the brain. This case report and other similar twin cases may help to understand the pathogenesis and to confirm the etiology of ZIKV as a teratogenic microorganism.

• • Molecular Epidemiology of Malaria in Cameroon and Côte d'Ivoire. XXXI. Kelch 13 Propeller Sequences in Plasmodium falciparum Isolates Before and After Implementation of Artemisinin-Based Combination Therapy

    Authors: Joseph Allico Djaman, Dagnogo Olefongo, Aristide Berenger Ako, Jocelyne Roman, Vincent Foumane Ngane, Leonardo K. Basco and Rachida Tahar

    Available online: 27 March 2017

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    Artemisinin-resistant malaria has not been reported from Africa, but resistance can possibly spread from Asia or arise independently in Africa. The emergence of artemisinin resistance in Africa can be monitored by molecular assay of Kelch 13 (K13) propeller sequences. A total of 251 archived DNA samples of Plasmodium falciparum isolates collected in 2002, 2003, and 2006 in Yaounde, Cameroon, and 47 samples collected in 2006 and 2013 in Abidjan, Côte d'Ivoire, were analyzed for K13-propeller sequence polymorphism. Only one isolate carried a mutant K13-propeller allele (E602D). None of the isolates carried the key mutant alleles (Y493H, R539T, I543T, and C580Y) associated with artemisinin resistance in Cambodia. The presence of the mutant allele was not correlated with in vitro response to dihydroartemisinin determined by the classical hypoxanthine incorporation assay. There was no evidence of K13 mutations associated with artemisinin resistance before and soon after the introduction of artemisinin-based combination therapies in Cameroon and Côte d'Ivoire.

• • Assessing the Contribution of Malaria Vector Control and Other Maternal and Child Health Interventions in Reducing All-Cause Under-Five Mortality in Zambia

    Authors: Marie Ng, K. Ellicott Colson, Nancy Fullman, Laura Dwyer-Lindgren, Tom Achoki, Matthew T. Schneider, Peter Mulenga, Peter Hangoma, Felix Masiye and Emmanuela Gakidou

    Available online: 15 February 2016

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    Under-five mortality in Zambia has declined since 1990, with reductions accelerating after 2000. Zambia's scale-up of malaria control is viewed as the driver of these gains, but past studies have not fully accounted for other potential factors. This study sought to systematically evaluate the impact of malaria vector control on under-five mortality. Using a mixed-effects regression model, we quantified the relationship between malaria vector control, other priority health interventions, and socioeconomic indicators and district-level under-five mortality trends from 1990 to 2010. We then conducted counterfactual analyses to estimate under-five mortality in the absence of scaling up malaria vector control. Throughout Zambia, increased malaria vector control coverage coincided with scaling up three other interventions: the pentavalent vaccine, exclusive breast-feeding, and prevention of mother-to-child transmission of HIV services. This simultaneous scale-up made statistically isolating intervention-specific impact infeasible. Instead, in combination, these interventions jointly accelerated declines in under-five mortality by 11% between 2000 and 2010. Zambia's scale-up of multiple interventions is notable, yet our findings highlight challenges in quantifying program-specific impact without better health data and information systems. As countries aim to further improve health outcomes, there is even greater need—and opportunity—to strengthen routine data systems and to develop more rigorous evaluation strategies.