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• • Cost-Effectiveness of Indoor Residual Spraying of Households with Insecticide for Malaria Prevention and Control in Tanzania

    Authors: Rachel Stelmach, Rajeev Colaço, Shabbir Llaji, Deborah McFarland and Richard Reithinger

    Available online: 16 July 2018

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    Using a decision-tree approach, we examined the cost-effectiveness of indoor residual spraying of households with insecticide (IRS) combined with insecticide-treated bed net (ITN) distribution (IRS + ITN), compared with ITN distribution alone in the programmatic context of mainland Tanzania. The primary outcome of our model was the expected economic cost to society per case of malaria averted in children ≤ 5 years of age. Indoor residual spraying of households with insecticide data came from a program implemented in northwest Tanzania from 2008 to 2012; all other data originated from the published literature. Through sensitivity and scenario analyses, the model also examined the effects of variations in insecticide resistance, malaria prevalence, and different IRS modalities. In the base case, IRS + ITN is expected to be more expensive and more effective than the ITN-only intervention (incremental cost per case averted [ICER]: $152.36). The number of IRS rounds, IRS insecticide costs, ITN use, malaria prevalence, and the probability that a child develops symptoms following infection drove the interventions’ cost-effectiveness. Compared with universal spraying, targeted spraying is expected to lead to a higher number of malaria cases per person targeted (0.211–0.256 versus 0.050–0.076), but the incremental cost per case of malaria averted is expected to be lower (ICER: $41.70). In a scenario of increasing pyrethroid resistance, the incremental expected cost per case of malaria averted is expected to increase compared with the base case (ICER: $192.12). Tanzania should pursue universal IRS only in those regions that report high malaria prevalence. If the cost per case of malaria averted of universal IRS exceeds the willingness to pay, targeted spraying could provide an alternative, but may result in higher malaria prevalence.

• • Accuracy, Ease of Use, Safety, and Acceptability of a 23-μL Conical Cup Blood Transfer Device for Use with Rapid Diagnostic Tests

    Authors: Sandra Incardona, Daniel J. Kyabayinze, David Bell, Bbale Ndawula, Marvis C. Kanyago, Magoma C. Mwancha-Kwasa and Iveth J. González

    Available online: 16 July 2018

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    Devices to safely transfer fixed amounts of finger prick blood to rapid diagnostic tests (RDTs) pose a significant challenge, especially in non-laboratory settings. Following the success of an “inverted cup device” for transfer of 5 μL blood, a prototype with a conical cup shape was developed for transfer of 20 μL blood, the amount needed for human immunodeficiency virus or human African trypanosomiasis (HAT) RDTs. This study determined the volume of blood transferred by this new blood transfer device (BTD) and compared its ease of use, safety, and acceptability with that of a plastic pipette when used by health workers (HWs) for HAT RDTs in northwestern Uganda. After a half-day training, 48 HWs had used the two BTDs with at least 10 patients. The conical cup BTD effectively transferred a mean of 22.76 μL of blood (standard deviation 3.31 μL). A significantly higher proportion of HWs were able to collect the full amount of blood using the conical cup BTD, as compared with the pipette (92.4% versus 74.2%, P < 0.001). In HW questionnaires, the conical cup BTD scored higher than the pipette in various aspects of ease of use and safety. In addition, HWs preferred the conical cup BTD (79%), indicating that it was easy to handle, made work faster, and increased their confidence in front of the patient. These findings suggest that the design of the conical cup BTD may be adapted for RDTs requiring 20 μL of blood to facilitate safe and accurate blood transfer.

• • Hepatitis B Surface Antigen Seroprevalence among Prevaccine and Vaccine Era Children in Bangladesh

    Authors: Repon C. Paul, Mahmudur Rahman, Eric Wiesen, Minal Patel, Kajal C. Banik, Ahmed R. Sharif, Sharmin Sultana, Mizanur Rahman, Jayantha Liyanage, Nihal Abeysinghe, Saleem Kamili, Trudy Murphy, Stephen P. Luby and Eric E. Mast

    Available online: 16 July 2018

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    Bangladesh introduced hepatitis B vaccine in a phased manner during 2003–2005 into the routine childhood vaccination schedule. This study was designed to evaluate the impact of the introduction of hepatitis B vaccine in Bangladesh by comparing hepatitis B surface antigen (HBsAg) prevalence among children born before and after vaccine introduction and to estimate the risk of vertical transmission of chronic hepatitis B virus (HBV) infection from mother to infant. We also evaluated the field sensitivity and specificity of an HBsAg point-of-care test strip. We selected a nationally representative sample of 2,100 prevaccine era and 2,100 vaccine era children. We collected a 5-mL blood sample from each child. One drop of blood was used to perform rapid HBsAg testing. If a child had a positive HBsAg test result with the rapid test, a blood sample was collected from the mother of the HBsAg-positive child and from the mothers of two subsequently enrolled HBsAg-negative children. All samples were tested for serologic markers of HBV infection using standard enzyme-linked immunosorbent assay. One (0.05%) child in the vaccine era group and 27 (1.2%; 95% confidence interval [CI]: 0.8–1.7%) children in the prevaccine era group were HBsAg positive. Mothers of HBsAg-positive children were more likely to be HBsAg positive than mothers of HBsAg-negative children (odds ratios = 4.7; 95% CI: 1.0–21.7%). Sensitivity of the HBsAg rapid test was 91.2% (95% CI: 76.6–98.1%) and specificity was 100% (95% CI: 99.9–100%). The study results suggest that even without a birth dose, the hepatitis B vaccine program in Bangladesh was highly effective in preventing chronic HBV infection among children.

• • Mentoring in Global Health: Formative Evaluation of Tuberculosis Research Training Programs in Ethiopia and Georgia

    Authors: Dawn L. Comeau, Kathryn Mishkin, Nestani Tukvadze, Zaza Avaliani, Russell R. Kempker, Lisa Sthreshley, Matthew J. Magee, Hannah Eisen, Damen Haile Mariam, Abraham Aseffa and Henry M. Blumberg

    Available online: 16 July 2018

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    Mentoring is a critical component of career development for research scientists and is related to mentee success both in terms of career selection and advancement. However, there are limited data on the role of mentoring in low- and middle-income countries (LMICs). Cross-cultural mentorship programs have the potential to foster the transfer of knowledge and the development of capacity to resource-poor settings. This formative evaluation explores the cultural context of mentoring in the countries of Georgia and Ethiopia. Results were used to build culturally relevant mentor training programs for the National Institutes of Health Fogarty International Center funded Global Infectious Diseases grants focused on tuberculosis (TB) research and research training. Four focus group discussions were conducted with research trainees and mentors to explore the perceptions of mentorship, identify obstacles for successful mentoring, and generate recommendations to strengthen mentoring in each program situated in a LMIC. Data revealed the barriers to mentoring in Ethiopia and Georgia included gaps in knowledge about mentoring roles and responsibilities, lack of knowledge about the responsibilities of the trainee in a mentoring relationship, and the need to set clear expectations between mentors and trainees. All of the focus group participants desired formal mentor training. These data informed six key components of the development and implementation of the mentor training programs in both countries. The topics included the following: a foundation in mentoring, establishing expectations between mentees and mentors, increasing interactions between mentees and mentors, additional mentor training, a case study curriculum, and methods of evaluating mentoring relationships.

• • First Report of Trypanosoma cruzi Infection in Salivary Gland of Bats from the Peruvian Amazon

    Authors: Fredy E. Villena, Luis A. Gomez-Puerta, Erik J. Jhonston, O. Melisa Del Alcazar, Jorge L. Maguiña, Christian Albujar, V. Alberto Laguna-Torres, Sergio E. Recuenco, Sarah-Blythe Ballard and Julia S. Ampuero

    Available online: 16 July 2018

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    In the Americas, 8 million people are infected with Chagas disease, and an additional 90 million people are at risk for infection. Little is known about the role bats play in the sylvatic transmission cycle of Trypanosoma cruzi, the parasite causing Chagas disease. Here, we captured bats in the villages of Palmiche, Pachacutec, Nuevo San Martin, and Mayuriaga located in the Datem del Marañon Province in Loreto, Peru. Venous blood samples were collected by cardiac puncture or from the upper extremities, and trypanosomatids were identified by microscopy and molecularly. We collected blood samples from 121 bats on filter paper for molecular studies and 111 slides for microscopic examination of thin and thick blood smears from 16 different bat species. The prevalence of trypanosomatids in all bats species was 34.7% (42/121) and the prevalence of T. cruzi was 4.1% (5/121). In hematophagous bat species, the prevalence of trypanosomatids and T. cruzi was 36.9% (27/73) and 2.7% (2/73), respectively. In non-hematophagous bats, the prevalences of trypanosomatids and T. cruzi were 31.2% (15/48) and 6.2% (3/48), respectively. Also, we confirm the presence of T. cruzi in salivary glands of hematophagous bats Diaemus youngi. These results suggest a sylvatic cycle of trypanosomatid transmission in which bats may harbor infectious T. cruzi parasites that could be transmitted to humans via hematophagous bat bites or salivary contamination by non-hematophagous bats of vegetables consumed by humans.

• • Characterizing Pediatric Tuberculosis with and without Human Immunodeficiency Virus Coinfection in Harare, Zimbabwe

    Authors: Michelle Earley, Joconiah Chirenda, Alexandra Highet, Hilda A. Mujuru and Zhenhua Yang

    Available online: 16 July 2018

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    Pediatric tuberculosis (TB) represents a major barrier to reducing global TB mortality, especially in countries confronting dual TB and human immunodeficiency virus (HIV) epidemics. Our study aimed to characterize pediatric TB epidemiology in the high-burden setting of Harare, Zimbabwe, both to fill the current knowledge gap around the epidemiology of pediatric TB and to indicate areas for future research and interventions. We analyzed de-identified data of 1,051 pediatric TB cases (0–14 years) found among a total of 11,607 TB cases reported in Harare, Zimbabwe, during 2011–2012. We performed Pearson’s χ2 test and multivariate logistic regression analysis to characterize pediatric TB and to assess predictors of HIV coinfection. Pediatric TB cases accounted for 9.1% of all TB cases reported during 2011–2012. Approximately 50% of pediatric TB cases were children younger than 5 years. Almost 60% of the under-5 age group were male, whereas almost 60% of the 10–14 age group were female. The overall HIV coinfection rate was 58.3%. Odds for HIV coinfection was higher for the 5–9 age group (adjusted odds ratio [AOR]: 2.77, 95% confidence interval [CI]: 1.97–3.94), the 10–14 group (AOR: 3.57, 95% CI: 2.52–5.11), retreatment cases (AOR: 6.17, 95% CI: 2.13, 26.16), and pulmonary TB cases (AOR: 2.39, 95% CI: 1.52, 3.75). In conclusion, our study generated evidence that pediatric TB, compounded by HIV coinfection, significantly impacts children in high-burden settings. The findings of our study indicate a critical need for targeted interventions.

• • Case Report: Delayed Diagnosis of Congenital Malaria by Plasmodium vivax in a Newborn of an Eritrean Woman with Varicella Infection

    Authors: Saba Gebremeskel Tekle, Angela Corpolongo, Alessandra D’Abramo, Maria Letizia Giancola, Marco Iannetta, Laura Scorzolini, Paola Marcozzi, Elsa Buffone, Giuseppina Liuzzi and Emanuele Nicastri

    Available online: 16 July 2018

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    Congenital malaria (CM) is uncommon in both malaria-endemic and non-endemic countries. It may be caused by any Plasmodium spp., although Plasmodium falciparum and Plasmodium vivax are the more frequent etiologic agents. We report a case of delayed diagnosis of CM by P. vivax in a newborn of an Eritrean primigravida. The mother developed pregnancy-related immunodepression and varicella-zoster viral infection 9 days before natural delivery; therefore, the child was admitted in the neonatal intensive care unit (NICU) to administer specific varicella-zoster immunoglobulin prophylaxis and for clinical monitoring. During the NICU stay, the newborn presented a febrile syndrome with vomiting, anemia, and thrombocytopenia. A P. vivax severe malaria diagnosis was made by detecting trophozoites in the thick and thin blood smears. The infant was successfully treated with intravenous artesunate and clindamycin. Our experience suggests that malaria diagnostic tests need to be included in routine blood analyses in newborns with febrile syndrome from mothers with an epidemiologic link to malaria-endemic areas.

• • Case Report: First Report of Autochthonous Human Cutaneous Myiasis Caused by Hypoderma lineatum in Europe

    Authors: Paola Rappelli, Antonio Varcasia, Arnoldo Vargiu and Antonio Scala

    Available online: 16 July 2018

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    We report a case of human cutaneous myiasis by Hypoderma lineatum, contracted by a farmer who never traveled outside Italy. Identification at species level has been performed by both morphological examination and sequencing of cytochrome c oxidase subunit I gene. This is the first description of human hypodermosis by H. lineatum contracted in Europe.

• • Case Report: Corneal Coinfection with Fungus and Amoeba: Report of Two Patients and Literature Review

    Authors: Joveeta Joseph, Sunita Chaurasia and Savitri Sharma

    Available online: 16 July 2018

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    We report two cases of corneal coinfection with Acanthamoeba and Fusarium sp. along with the review of published literature. A 35-year-old woman and 65-year-old man presented to the institute with corneal ulcer refractory for treatment with topical antibiotics. Microbiological examination revealed the presence of Acanthamoeba cysts along with septate, hyaline fungal filaments. After emergency therapeutic penetrating keratoplasty (TPK) in both, the corneal tissue was sent for histopathologic examination, which confirmed the presence of Acanthamoeba and fungal coinfection. One patient had a recurrence of fungal infection after TPK. In subjects with a rapid progression of mycotic ulcer, coinfection with other microorganisms including Acanthamoeba should be suspected. The two cases presented here emphasize the importance of microbiology in making prompt diagnosis and appropriate management of these cases at an early stage.

• • Comprehensive Assessment of a Hotspot with Persistent Bancroftian Filariasis in Coastal Sri Lanka

    Authors: Ramakrishna U. Rao, Sandhya D. Samarasekera, Kumara C. Nagodavithana, Charles W. Goss, Manjula W. Punchihewa, Tharanga D. M. Dassanayaka, Udaya S. B. Ranasinghe, Devika Mendis and Gary J. Weil

    Available online: 16 July 2018

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    The Sri Lankan Anti-Filariasis campaign distributed five rounds of mass drug administration (MDA with diethylcarbamazine plus albendazole) to some 10 million people in eight districts between 2002 and 2006. Sri Lanka was recognized by the WHO for having eliminated lymphatic filariasis (LF) as a public health problem in 2016. However, recent studies by our group documented pockets with persistent LF in coastal Sri Lanka, especially in Galle district. The present study was performed to reexamine an area previously identified as a potential hotspot for persistent LF (Balapitiya Public Health Inspector, population 17,500). A community survey documented high rates for circulating filarial antigenemia (3%, confidence interval [CI]: 1.8–4.9) and microfilaremia (1%, CI: 0.5–2.5%). Circulating filarial antigenemia rates were 2.8-fold higher in males than females. High prevalence was also observed for anti-filarial antibodies in young children (5.7%, CI: 3.7–8.4%) and for filarial DNA in vector mosquitoes (5.2%, CI: 4.2–6.3%). Spatial data showed that persistent LF was dispersed across the entire study area. Other studies showed that persistent LF was not limited to Balapitiya and not solved by additional rounds of MDA. Molecular xenomonitoring studies conducted in 2016 in 22 of 168 Public Health Midwife areas in the coastal Galle evaluation unit (approximate population 600,000) found that 179 of 660 (27%) pools of Culex collected from all areas were positive for Wuchereria bancrofti DNA by qPCR; the estimated infection rate in mosquitoes was 1.26%, CI: 1.0–1.5%. Interventions other than routine MDA will be required to remove LF hotspots in Balapitiya and in other areas in coastal Sri Lanka.

• • Salmonella enterica serovars Panama and Arechavaleta, Risk Factors for Invasive Non-Typhoidal Salmonella Disease in Guadeloupe, French West Indies

    Authors: Stephanie Guyomard-Rabenirina, Blandine Muanza, Sylvaine Bastian, Edith Malpote, Pauline Jestin, Meggie Guerrin, Antoine Talarmin, François-Xavier Weill, Arnaud Legrand and Sebastien Breurec

    Available online: 16 July 2018

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    A retrospective study was conducted to identify the risk factors associated with Salmonella enterica bacteremia in infants and children in Guadeloupe, French West Indies. The 171 patients with S. enterica infection seen between 2010 and 2014 included 155 (90.6%) with acute gastroenteritis, of whom 42 (27.1%) had concomitant bacteremia and 16 (9.4%) with primary bacteremia. Most cases (97.7%) were in infants and children with no underlying health condition. Two subspecies were recovered: enterica (N = 161, 94.2%) and houtenae (N = 10, 5.8%). All but one (serovar Typhi) were non-typhoidal Salmonella. The most common serovars were Panama (N = 57, 33.3% of isolates) and Arechavaleta (N = 28, 16.4%). Univariate analysis showed a strong association only between age > 6 months and infection with the Panama or Arechavaleta serovar (P = 0.002). The rate of resistance to all classes of antibiotics during the study period was low (< 15%); however, the detection of one extended-spectrum beta-lactamase–producing S. enterica strain highlights the need for continued monitoring of antimicrobial drug susceptibility. Infection with Panama (P < 0.001) or Arechavaleta (P < 0.001) serovar was significantly associated with bacteremia in a multivariate analysis. These serovars are probably poorly adapted to humans or are more virulent. A delay between onset of symptoms and hospital admission > 5 days (P = 0.01), vomiting (P = 0.001), and increased respiratory rate (P = 0.001) contributed independently to bacteremia in the multivariate analysis. Thus, if non-typhoidal infection is suspected, blood should be cultured and antibiotic treatment initiated in all patients who meet these criteria.

• • Controlled Human Malaria Infection with Graded Numbers of Plasmodium falciparum NF135.C10- or NF166.C8-Infected Mosquitoes

    Authors: Marijke C. C. Langenberg, Linda J. Wammes, Matthew B. B. McCall, Else M. Bijker, GeertJan van Gemert, Wouter Graumans, Marga van de Vegte, Karina Teelen, Cornelis C. Hermsen, Rob Koelewijn, Jaap J. van Hellemond, Perry J. J. van Genderen and Robert W. Sauerwein

    Available online: 16 July 2018

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    Controlled human malaria infections (CHMIs) with Plasmodium falciparum (Pf) parasites are well established. Exposure to five Pf (NF54)-infected Anopheles mosquitoes results in 100% infection rates in malaria-naïve volunteers. Recently Pf clones NF135.C10 and NF166.C8 were generated for application in CHMIs. Here, we tested the clinical infection rates of these clones, using graded numbers of Pf-infected mosquitoes. In a double-blind randomized trial, we exposed 24 malaria-naïve volunteers to bites from one, two, or five mosquitoes infected with NF135.C10 or NF166.C8. The primary endpoint was parasitemia by qPCR. For both strains, bites by five infected mosquitoes resulted in parasitemia in 4/4 volunteers; 3/4 volunteers developed parasitemia after exposure to one or two infected mosquitoes infected with either clone. The prepatent period was 7.25 ± 4.0 days (median ± range). There were no serious adverse events and comparable clinical symptoms between all groups. These data confirm the eligibility of NF135.C10 and NF166.C8 for use in CHMI studies.

• • Anthropometry and Malaria among Children in Niger: A Cross-Sectional Study

    Authors: Kieran S. O’Brien, Abdou Amza, Boubacar Kadri, Beido Nassirou, Sun Y. Cotter, Nicole E. Stoller, Sheila K. West, Robin L. Bailey, Travis C. Porco, Bruce D. Gaynor, Thomas M. Lietman and Catherine E. Oldenburg

    Available online: 16 July 2018

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    The complex relationship between malnutrition and malaria affects morbidity and mortality in children younger than 5 years, particularly in parts of sub-Saharan Africa where these conditions occur together seasonally. Previous research on this relationship has been inconclusive. Here, we examine the association between anthropometric indicators and malaria infection in a population-based sample of children younger than 5 years in Niger. This cross-sectional study is a secondary analysis of a cluster-randomized trial comparing treatment strategies for trachoma in Niger. We included children aged 6–60 months residing in the 48 communities enrolled in the trial who completed anthropometric and malaria infection assessments at the final study visit. We evaluated the association between anthropometric indicators, including height-for-age z-score (HAZ) and weight-for-age z-score (WAZ) and indicators of malaria infection, including malaria parasitemia and clinical malaria. In May 2013, we collected data from 1,649 children. Of these, 780 (47.3%) were positive for malaria parasitemia and 401 (24.3%) had clinical malaria. In models of malaria parasitemia, the adjusted odds ratio (aOR) was 1.05 (95% confidence interval [CI]: 1.00–1.10) for HAZ and 1.07 (95% CI: 0.99, 1.15) for WAZ. In models of clinical malaria, the aOR was 1.07 (95% CI: 1.02–1.11) for HAZ and 1.09 (95% CI: 1.01–1.19) for WAZ. Overall, we did not find evidence of an association between most anthropometric indicators and malaria infection. Greater height may be associated with an increased risk of clinical malaria.

• • Operational Performance of the Onchocerca volvulus “OEPA” Ov16 ELISA Serological Assay in Mapping, Stop Mass Drug Administration, and Posttreatment Surveillance Surveys

    Authors: Frank O. Richards Jr.,, Moses Katabarwa, Firdaweke Bekele, Zerihun Tadesse, Aderajew Mohammed, Mauricio Sauerbrey, Alfredo Dominguez-Vazquez, Mario A. Rodriguez-Perez, Nadia A. Fernández-Santos, Nidia Rizzo, Harland R. Schuler Martínez, Raquel Lovato Silva, Zoraida Morales Monroy, Peace Habomugisha, David W. Oguttu, Issam M. A. Zarroug, Nabil A. Aziz and Thomas R. Unnasch

    Available online: 16 July 2018

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    Onchocerciasis is a neglected tropical disease targeted for elimination. The World Health Organization (WHO) has developed guidelines for the verification of onchocerciasis elimination that include entomological and epidemiological criteria. The latter require demonstrating with statistical confidence that the infection prevalence in children is less than 0.1%, necessitating an assay with a high degree of specificity. We present an analysis of the performance of the Onchocerciasis Elimination Program for the Americas (OEPA) version of the Ov16 ELISA when used under operational conditions. In Africa and Latin America, the assay demonstrated 99.98% specificity in 69,888 children in 20 foci where transmission was believed to be interrupted. The assay produced a prevalence estimate equal to that of skin snip microscopy when applied in putatively hypo-endemic zones of Ethiopia. The OEPA Ov16 ELISA demonstrated the specificity required to be effectively deployed to verify transmission elimination under the WHO guidelines, while exhibiting a sensitivity equivalent to skin snip microscopy to identify hypo-endemic areas.

• • Effect of Antibiotics on Short-Term Growth among Children in Burkina Faso: A Randomized Trial

    Authors: Ali Sié, Clarisse Dah, Lucienne Ouermi, Charlemagne Tapsoba, Pascal Zabre, Till Bärnighausen, Elodie Lebas, Ahmed M. Arzika, Blake M. Snyder, Travis C. Porco, Thomas M. Lietman, Jeremy D. Keenan and Catherine E. Oldenburg

    Available online: 16 July 2018

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    Antibiotics improve both weight and height gain in randomized trials of preschool children with preexisting morbidity. Here, we assess the effect of a short course of three different antibiotics (amoxicillin, azithromycin, and cotrimoxazole) on short-term linear and ponderal growth in a population-based sample of preschool children in rural Burkina Faso. We randomized households with at least two children in the Nouna district, Burkina Faso, to a 5-day course of amoxicillin, azithromycin, cotrimoxazole, or placebo. Within each antibiotic-randomized household, one child was randomly assigned to receive the antibiotic and the other to receive the placebo. Weight and height measurements were taken at baseline and 30 days following the last study medication dose. Weight-for-height Z (WHZ), height-for-age Z (HAZ), and weight-for-age Z (WAZ) scoreswere calculated based on the 2006 World Health Organization standards. Of the 124 households and 248 children enrolled, 229 had anthropometry measurements at 1 month and were analyzed. Children randomized to amoxicillin gained significantly more weight compared with both the placebo household (mean difference 317 g, 95% CI: 115–519 g) and placebo sibling (mean difference 315 g, 95% CI: 147–482 g) controls. Growth velocity in g/kg/day, and WHZ and WAZ scores were higher in amoxicillin-treated children compared with placebo households and siblings. There were no differences in weight gain in children randomized to azithromycin or cotrimoxazole compared with placebo households or placebo siblings. There were no differences in height gain or HAZ across any of the study arms. Amoxicillin may have short-term growth-promoting effects in healthy children.

• • Case Report: A Cluster of Plasmodium falciparum Malaria Cases among Thai Workers in Gembu, Nigeria

    Authors: Wasin Matsee, Lapakorn Chatapat, Kesinee Chotivanich and Watcharapong Piyaphanee

    Available online: 16 July 2018

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    Although falciparum malaria is an important risk among travelers to sub-Saharan Africa, many travelers remain unaware of this risk. In October 2015, we found a cluster of imported Plasmodium falciparum malaria cases among Thai gem mine workers in Nigeria; none had received malaria chemoprophylaxis or information regarding malaria risk. The index case developed fever and visited our hospital on arrival day in Thailand after his 3-week stay in Nigeria. Plasmodium falciparum was found in his blood. He recovered completely 3 days post-admission. After we requested he contact his colleagues in Nigeria regarding malaria risk, we found that three of his five colleagues currently had fever, were diagnosed with malaria, and were being treated in a local hospital. Two were successfully treated in Nigeria. Although their blood films were negative for malaria, we could confirm that they recently had malaria because the polymerase chain reaction (PCR) was still positive for P. falciparum. Tragically, the last febrile case died in Nigeria 6 days post-admission, after developing jaundice and alteration of consciousness. The two colleagues without fever symptoms were also tested by PCR, which was negative for malaria. In conclusion, we found that four of six workers had malaria in this cluster, which was equal to 66.7% attack rate. There is an urgent need to raise awareness of malaria among workers in highly endemic areas. Clinical practice for travelers who are ill on their return should not only focus on individual cases but also consider potential disease clusters.

• • Epidemiology of Plasmodium vivax Malaria Infection in Nepal

    Authors: Komal Raj Rijal, Bipin Adhikari, Prakash Ghimire, Megha Raj Banjara, Borimas Hanboonkunupakarn, Mallika Imwong, Kesinee Chotivanich, Kedar Prasad Ceintury, Bibek Kumar Lal, Garib Das Thakur, Nicholas P. J. Day, Nicholas J. White and Sasithon Pukrittayakamee

    Available online: 16 July 2018

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    Malaria is endemic in the southern plain of Nepal which shares a porous border with India. More than 80% cases of malaria in Nepal are caused by Plasmodium vivax. The main objective of this study was to review the epidemiology of P. vivax malaria infections as recorded by the national malaria control program of Nepal between 1963 and 2016. National malaria data were retrieved from the National Malaria program in the Ministry of Health, Government of Nepal. The epidemiological trends and malariometric indicators were analyzed. Vivax malaria has predominated over falciparum malaria in the past 53 years, with P. vivax malaria comprising 70–95% of the annual malaria infections. In 1985, a malaria epidemic occurred with 42,321 cases (82% P. vivax and 17% Plasmodium falciparum). Nepal had experienced further outbreaks of malaria in 1991 and 2002. Plasmodium falciparum cases increased from 2005 to 2010 but since then declined. Analyzing the overall trend between 2002 (12,786 cases) until 2016 (1,009 cases) shows a case reduction by 92%. The proportion of imported malaria cases has increased from 18% of cases in 2001 to 50% in 2016. The current trends of malariometric indices indicate that Nepal is making a significant progress toward achieving the goal of malaria elimination by 2025. Most of the cases are caused by P. vivax with imported malaria comprising an increasing proportion of cases. The malaria control program in Nepal needs to counter importation of malaria at high risk areas with collaborative cross border malaria control activities.

• • Antibiotic Therapy in Adults with Malaria: High Rate of Clinically Significant Bacteremia in Hospitalized Adults Diagnosed with Falciparum Malaria

    Authors: Ne Myo Aung, Phyo Pyae Nyein, Thu Ya Htut, Zaw Win Htet, Tint Tint Kyi, Nicholas M. Anstey, Mar Mar Kyi and Josh Hanson

    Available online: 16 July 2018

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    It has been believed that concomitant bacteremia is uncommon in adults hospitalized with falciparum malaria. Accordingly, the World Health Organization treatment guidelines presently only recommended additional antibacterial therapy in these patients if they have a clinical syndrome compatible with serious bacterial infection. Admission blood cultures were collected from 20 consecutive adults in Myanmar, hospitalized with a positive immunochromatographic test and blood film, suggesting a diagnosis of falciparum malaria; four (20%) had bacteremia with a clinically significant pathogen. These case series’ data were pooled with a previously published multicenter study from Myanmar which had also collected blood cultures in adults hospitalized with a diagnosis of falciparum malaria. Among 87 patients in the two studies, 13 (15%) had clinically significant bacteremia on admission, with Gram-negative organisms in 10 (77%) and Staphylococcus aureus in the remaining three (23%). Bacteremic patients had more severe disease than non-bacteremic patients (median [interquartile range] RCAM score 2 [1–4] versus 1 [1–2], P = 0.02) and were more likely to die (2/13 [15%] versus 1/74 [1%], P = 0.02). However, bacterial coinfection was suspected clinically in a minority of bacteremic patients (5/13 [38%] compared with 13/70 [19%] of non-bacteremic patients, P = 0.11). Concomitant bacteremia in adults diagnosed with falciparum malaria may be more common than previously believed and is difficult to identify clinically in resource-poor settings. Death is more common in these patients, suggesting that clinicians should have a lower threshold for commencing empirical antibacterial therapy in adults diagnosed with falciparum malaria in these locations than is recommended presently.

• • Melioidosis is in the Americas: A Call to Action for Diagnosing and Treating the Disease

    Authors: Alfredo G. Torres, Franco E. Montufar, Jay E. Gee, Alex R. Hoffmaster, Mindy G. Elrod, Carolina Duarte-Valderrama, Monica G. Huertas and David E. Blaney

    Available online: 16 July 2018

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    Melioidosis, a disease caused by the pathogen Burkholderia pseudomallei, is a significant underreported endemic disease found in tropical countries worldwide. Recent studies have demonstrated that human melioidosis cases have been increasingly recognized in the Americas. Therefore, the first Scientific Reunion of Melioidosis in the Americas was organized in Colombia, with the participation of health authorities of 11 Latin American countries and the United States. This report summarizes the topics reviewed during the meeting, including how to identify human infections and properly diagnose them, with the goal of increasing recognition of the disease in the Americas.

• • Antibiotic Prophylaxis for Melioidosis in Patients Receiving Hemodialysis in the Tropics? One Size Does Not Fit All

    Authors: Ken W. T. Chau, Simon Smith, Katherine Kang, Shyam Dheda and Josh Hanson

    Available online: 16 July 2018

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    Melioidosis has a high case fatality rate and is more common in patients with chronic kidney disease. Some authors recommended trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis for all hemodialysis (HD) patients during the wet season in melioidosis-endemic regions. Historical data were reviewed to determine if TMP/SMX prophylaxis was warranted in the HD population of Far North Queensland, Australia. Between 1997 and 2017, there were 242 culture-confirmed cases of melioidosis in the region, three (1.2%) occurred in HD patients; all survived without intensive care support. During the study period, there were 843 HD patients in the region with 3,024 cumulative patient years of risk. Even assuming 100% efficacy, it would have been necessary to prescribe TMP/SMX for 1,008 patient years to prevent one case of melioidosis. Given the significant additional cost and potentially life-threatening side effects of TMP/SMX therapy, clinicians should review the local epidemiology of melioidosis before the implementation of universal TMP/SMX prophylaxis in their HD population.

• • Genomic Investigation of a Mycobacterium tuberculosis Outbreak Involving Prison and Community Cases in Florida, United States

    Authors: Marie Nancy Séraphin, Xavier Didelot, David J. Nolan, Justin R. May, Md. Siddiqur Rahman Khan, Ellen R. Murray, Marco Salemi, J. Glenn Morris Jr. and Michael Lauzardo

    Available online: 09 July 2018

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    We used whole-genome sequencing to investigate a tuberculosis outbreak involving U.S.-born persons in the prison system and both U.S.- and foreign-born persons in the community in Florida over a 7-year period (2009–2015). Genotyping by spacer oligonucleotide typing and 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat suggested that the outbreak might be clonal in origin. However, contact tracing could not link the two populations. Through a multidisciplinary approach, we showed that the cluster involved distinct bacterial transmission networks segregated by country of birth. The source strain is of foreign origin and circulated in the local Florida community for more than 20 years before introduction into the prison system. We also identified novel transmission links involving foreign and U.S.-born cases not discovered during contact investigation. Our data highlight the potential for spread of strains originating from outside the United States into U.S. “high-risk” populations (such as prisoners), with subsequent movement back to the general community.

• • Non-Respiratory and Non-Diarrheal Causes of Acute Febrile Illnesses in Children Requiring Hospitalization in a Tertiary Care Hospital in North India: A Prospective Study

    Authors: Abdul Rauf, Sunit Singhi, Karthi Nallasamy, Mandeep Walia and Pallab Ray

    Available online: 09 July 2018

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    Acute febrile illnesses (AFIs) in children from the developing world can have varying etiologies. Awareness of local epidemiology helps in prioritizing investigations and empiric treatment. This prospective study was carried out in a tertiary care center in North India, aiming to determine the burden, etiology, and outcome of AFI other than pneumonia and diarrhea in hospitalized children. A total of 613 consecutive children aged 3 months to 12 years with febrile illness of < 7 days during four selected months of 2014 representing different seasons were screened for eligibility. Those with acute respiratory diseases (N = 175, 28.5%) and diarrheal illness (N = 46, 7.5%) were excluded and 217 children were enrolled. Mean (standard deviation) age was 4.8 (3.4) years. Nearly half (N = 91, 41.9%) presented in post-monsoon season. Diagnosis could be established in 187 (86.2%) children. Acute CNS infections were the most common (N = 54, 24.8%). Among specific infections, scrub typhus was the most frequent (N = 23, 10.5%) followed by malaria (N = 14, 6.4%), typhoid (N = 14, 6.5%), and viral hepatitis (N = 13, 6.0%). Blood culture had a low (6.5%) yield; Salmonella typhi (N = 6) and Staphylococcus aureus (N = 5) were the common isolates. Serological tests were helpful in 50 (23%) cases. In multivariate analysis, hepatomegaly and/or splenomegaly independently predicted scrub typhus. Mortality rate was 10.1%. We conclude that AFI other than pneumonia and diarrhea are a significant burden and follow a seasonal trend. Scrub typhus has emerged as an important etiology of childhood AFIs in northern India. Periodic review of regional epidemiology will help in understanding the changing pattern of infectious diseases.

• • Accuracy of a Rapid Diagnostic Test Based on Antigen Detection for the Diagnosis of Cutaneous Leishmaniasis in Patients with Suggestive Skin Lesions in Morocco

    Authors: Issam Bennis, Kristien Verdonck, Nora el Khalfaoui, Myriam Riyad, Hajiba Fellah, Jean-Claude Dujardin, Hamid Sahibi, Souad Bouhout, Gert Van der Auwera and Marleen Boelaert

    Available online: 09 July 2018

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    In rural areas in Morocco, diagnosing cutaneous leishmaniasis (CL) can be challenging. We evaluated the accuracy of a rapid diagnostic test (RDT) based on antigen detection, CL Detect Rapid Test™ (Inbios International Inc., Seattle, WA), in this setting. We consecutively recruited patients with new skin ulcers in nine primary health centers. We took a dental broach sample for the RDT and two other tissue samples by scraping the border and center of the lesion with a scalpel and smearing it on a slide. We duplicated each smear by pressing a clean slide against it and processed the slides by using microscopy, polymerase chain reaction (PCR) internal transcribed spacer 1, and kDNA minicircle PCR. In a subgroup with positive PCR, the Leishmania species was identified using PCR-restriction fragment length polymorphism and PCR-sequencing of hsp70 genes. A participant with positive microscopy and/or PCR was considered a confirmed CL case. We computed sensitivity (Se) and specificity (Sp) of the RDT compared with this reference standard (ClinicalTrials.gov registration: NCT02979002). Between December 2016 and July 2017, we included 219 patients, 50% of them were under 18 years old. Rapid diagnostic test Se was 68% [95% confidence interval (CI): 61–74], Sp 94% [95% CI: 91–97], positive predictive value 95% [95% CI: 92–98], and negative predictive value 64% [95% CI: 58–70]. Despite its low Se, this novel RDT is a useful addition to clinical management of CL in Morocco, especially in isolated localities. Rapid diagnostic test–positive lesions can be treated as CL; but when RDT negative, microscopy should be performed as a second step. The Se of the RDT can probably be optimized by improving the sampling procedure.

• • Relative Contribution of Schistosomiasis and Malaria to Anemia in Western Kenya

    Authors: Emily M. Valice, Ryan E. Wiegand, Pauline N. M. Mwinzi, Diana M. S. Karanja, John M. Williamson, Elizabeth Ochola, Aaron Samuels, Jennifer R. Verani, Juan S. Leon, W. Evan Secor and Susan P. Montgomery

    Available online: 09 July 2018

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    Because anemia is one of the markers of morbidity associated with schistosomiasis, it has been proposed as a potential measure to evaluate the impact of control programs. However, anemia is also a common consequence of malaria, and schistosomiasis and malaria are often co-endemic. To estimate the attributable fraction of anemia due to Schistosoma mansoni and Plasmodium falciparum infections, we applied a log-binomial model to four studies measuring these parameters of a combined 5,849 children in western Kenya. In our studies, malaria contributed 23.3%, schistosomiasis contributed 6.6%, and co-infection contributed 27.6% of the anemia. We conclude that in areas where S. mansoni and P. falciparum are co-endemic, the contribution of schistosomiasis to anemia is masked by anemia resulting from malaria, thus limiting anemia as a useful measure for schistosomiasis control programs in these settings.

• • Seroepidemiology of Dengue, Zika, and Yellow Fever Viruses among Children in the Democratic Republic of the Congo

    Authors: Alexandra C. Willcox, Matthew H. Collins, Ramesh Jadi, Corinna Keeler, Jonathan B. Parr, Dieudonné Mumba, Melchior Kashamuka, Antoinette Tshefu, Aravinda M. de Silva and Steven R. Meshnick

    Available online: 09 July 2018

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    Flaviviruses such as Zika, dengue, and yellow fever cause epidemics throughout the tropics and account for substantial global morbidity and mortality. Although malaria and other vector-borne diseases have long been appreciated in Africa, flavivirus epidemiology is incompletely understood. Despite the existence of an effective vaccine, yellow fever continues to cause outbreaks and deaths, including at least 42 fatalities in the Democratic Republic of the Congo (DRC) in 2016. Here, we leveraged biospecimens collected as part of the nationally representative 2013–2014 Demographic and Health Survey in the DRC to examine serological evidence of flavivirus infection or vaccination in children aged 6 months to 5 years. Even in this young stratum of the Congolese population, we find evidence of infection by dengue and Zika viruses based on results from enzyme-linked immunosorbent assay and neutralization assay. Surprisingly, there was remarkable discordance between reported yellow fever vaccination status and results of serological assays. The estimated seroprevalences of neutralizing antibodies against each virus are yellow fever, 6.0% (95% confidence interval [CI] = 4.6–7.5%); dengue, 0.4% (0.1–0.9%); and Zika, 0.1% (0.0–0.5%). These results merit targeted, prospective studies to assess effectiveness of yellow fever vaccination programs, determine flavivirus seroprevalence across a broader age range, and investigate how these emerging diseases contribute to the burden of acute febrile illness in the DRC.

• • Case Report: Orbital Tumor Revealing Adult T-Cell Leukemia/Lymphoma Associated with Human T-Cell Lymphotropic Virus Type-1

    Authors: Selim Farès, Rabih Hage, Jean Pegliasco, Samy Chraibi and Harold Merle

    Available online: 02 July 2018

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    Adult T-cell Leukemia/Lymphoma (ATLL) is a sight- and life-threatening complication of human T-cell lymphotropic virus type 1 (HTLV-1) infection. Ophthalmic manifestations include uveitis, optic nerve oedema, retinal vasculitis, and lymphomatous infiltration. Orbital lesions are rare. We report the case of an orbital tumor revealing systemic ATLL in a 45-year-old Dominican patient who died despite treatment. Apart from late-grade cutaneous T-cell lymphoma, ATLL is the only T-lymphoma to develop in the orbit. Diagnosis is based on serologic evidence of HTLV-1 infection, cytology, and blood sample analysis. Biopsy is deemed necessary. Given the poor prognosis of ATLL and the worldwide presentation of HTLV-1, physicians should consider ATLL in the differential diagnosis of orbital malignant tumor and look for HTLV-1 infection in populations at risk.

• • Important Clinical Features of Japanese Spotted Fever

    Authors: Masamitsu Noguchi, Shizuka Oshita, Naohisa Yamazoe, Mitsukazu Miyazaki and Yousuke C. Takemura

    Available online: 02 July 2018

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    Japanese spotted fever (JSF) is a zoonosis transmitted by ticks carrying the pathogen Rickettsia japonica. The classic triad of JSF symptoms is high fever, erythema, and tick bite eschar. About 200 people in Japan develop the disease every year. Japanese spotted fever is also a potentially fatal disease. At Minami-Ise Municipal Hospital in Japan, 55 patients were diagnosed with JSF from 2007 to 2015, which was equivalent to 4.3% of the total JSF cases in Japan. In this retrospective study, we examined the medical records of these 55 JSF cases. Fever, erythema, eschar, and elevated C-reactive protein (CRP) are characteristic clinical features of the disease. We confirmed four of these in the reviewed cases; however, eschar was not present in occasional cases. We confirmed that eosinopenia appeared in nearly all cases. Using fever, erythema, elevated CRP, and eosinopenia in diagnostic screening, our positivity rate was 90.9%. In our clinical practice, including eosinopenia improves the initial diagnosis of JSF.

• • Dried Blood Spots for Global Health Diagnostics and Surveillance: Opportunities and Challenges

    Author: Mark D. Lim

    Available online: 02 July 2018

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    There is increasing interest in using dried blood spot (DBS) cards to extend the reach of global health and disease surveillance programs to hard-to-reach populations. Conceptually, DBS offers a cost-effective solution for multiple use cases by simplifying logistics for collecting, preserving, and transporting blood specimens in settings with minimal infrastructure. This review describes methods to determine both the reliability of DBS-based bioanalysis for a defined use case and the optimal conditions that minimize pre-analytical sources of data variability. Examples by the newborn screening, drug development, and global health communities are provided in this review of published literature. Sources of variability are linked in most cases, emphasizing the importance of field-to-laboratory standard operating procedures that are evidence based and consider both stability and efficiency of recovery for a specified analyte in defining the type of DBS card, accessories, handling procedures, and storage conditions. Also included in this review are reports where DBS was determined to not be feasible because of technology limitations or physiological properties of a targeted analyte.

• • A Systematic Review and Meta-Analysis of the Association between Water, Sanitation, and Hygiene Exposures and Cholera in Case–Control Studies

    Authors: Marlene Wolfe, Mehar Kaur, Travis Yates, Mark Woodin and Daniele Lantagne

    Available online: 02 July 2018

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    Case–control studies are conducted to identify cholera transmission routes. Water, sanitation, and hygiene (WASH) exposures can facilitate cholera transmission (risk factors) or interrupt transmission (protective factors). To our knowledge, the association between WASH exposures and cholera from case–control studies has not been systematically analyzed. A systematic review was completed to close this gap, including describing the theory of risk and protection, developing inclusion criteria, searching and selecting studies, assessing quality of evidence, and summarizing associations between cholera and seven predicted WASH protective factors and eight predicted WASH risk factors using meta-analysis and sensitivity analysis. Overall, 47 articles describing 51 individual studies from 30 countries met the inclusion criteria. All eight predicted risk factors were associated with higher odds of cholera (odds ratio [OR] = 1.9–5.6), with heterogeneity (I 2) of 0–92%. Of the predicted protective factors, five of seven were associated with lower odds of cholera (OR = 0.35–1.4), with heterogeneity of 57–91%; exceptions were insignificant associations for improved water source (OR = 1.1, heterogeneity 91%) and improved sanitation (OR = 1.4, heterogeneity 68%). Results were robust; 3/70 (5%) associations changed directionality or significance in sensitivity analysis. Meta-analysis results highlight that predicted risk factors are associated with cholera; however, predicted protective factors are not as consistently protective. This variable protection is attributed to 1) cholera transmission via multiple routes and 2) WASH intervention implementation quality variation. Water, sanitation, and hygiene interventions should address multiple transmission routes and be well implemented, according to international guidance, to ensure that field effectiveness matches theoretical efficacy. In addition, future case–control studies should detail WASH characteristics to contextualize results.

• • Endotoxin at the Maternal–Fetal Interface in a Resource-Constrained Setting: Risk Factors and Associated Birth Outcomes

    Authors: Emily A. McDonald, Ronald Stuart, Ayush Joshi, Hannah W. Wu, Remigio M. Olveda, Luz P. Acosta, Veronica Tallo, Palmera I. Baltazar, Jeffrey A. Bailey, Jonathan D. Kurtis and Jennifer F. Friedman

    Available online: 02 July 2018

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    Low- and middle-income countries (LMICs) carry a high burden of infectious diseases associated with impaired gut integrity, leading to microbial translocation. Pregnancies in this setting are at high risk of fetal growth restriction (FGR). We examined the association among specific risk factors for impaired gut integrity (schistosomiasis, hookworm infection, and alcohol consumption), blood endotoxin levels, and FGR. Endotoxins, LPS-binding proteins (LBPs), and cytokines were measured in blood from women at 32 weeks gestation, the maternal–fetal interface (MFI) at delivery, and cord blood at delivery. Resolution of schistosomiasis had no impact on endotoxin levels; however, maternal hookworm infection and alcohol consumption were associated with modest increases in endotoxin at the MFI. Cytokines responses within the maternal peripheral blood and blood from the MFI were positively associated with endotoxins, but many cord blood cytokines were negatively associated with endotoxins. Newborns with FGR also had higher levels of endotoxins at the MFI. Risk factors for microbial translocation may lead to increased levels of endotoxins at the MFI, which may contribute to poor growth in utero.

• • Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in a Malaria-Endemic Area of Papua New Guinea

    Authors: Nigani Willie, Peter A. Zimmerman and Rajeev K. Mehlotra

    Available online: 02 July 2018

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    Histidine-rich protein 2 of Plasmodium falciparum (PfHRP2) forms the basis of many current malaria rapid diagnostic tests (RDTs). It is concerning that there are parasites that lack part or all of the pfhrp2 gene, and thus do not express the PfHRP2 protein; such parasites are not identifiable by PfHRP2-detecting RDTs. Very limited information is available regarding pfhrp2 genetic variation in Papua New Guinea (PNG). In the present study, this gene variation was evaluated using 169 samples previously collected from the Wosera area in East Sepik Province of PNG. Molecular diagnosis of these samples showed that 81% were infected, and P. falciparum was present in 91% of those infected samples. One hundred and twenty samples were amplified for pfhrp2 exon-2, from which 12 randomly selected amplicons were sequenced, yielding 18 sequences, all of which were unique. Baker repeat type 2 × type 7 numbers ranged from 0 to 108. Epitope mapping analysis revealed that three major epitopes, DAHHAHHA, AHHAADAHHA, and AHHAADAHH, were present in high prevalence and frequencies. These major epitopes have been shown to be recognized by the monoclonal antibodies 3A4 and PTL-3 (DAHHAHHA), C1-13 (AHHAADAHHA), and S2-5 and C2-3 (AHHAADAHH). This study provides further information on the high genetic variation of pfhrp2 and its unclear relationship with prediction of RDT detection sensitivity, and identifies major epitopes in this gene from PNG. These results could be relevant and useful to understand the genetic diversity of this gene and the performance of current and future RDTs in this malarious region of the world.

• • The Effect of Nonrandom Mating on Wolbachia Dynamics: Implications for Population Replacement and Sterile Releases in Aedes Mosquitoes

    Authors: Heng Lin Yeap, Nancy Margaret Endersby-Harshman and Ary Anthony Hoffmann

    Available online: 02 July 2018

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    Wolbachia bacteria are known to cause deviations from random mating and affect sperm competition (SC) in some of their arthropod hosts. Because these effects could influence the effectiveness of Wolbachia in mosquito population replacement and suppression programs, we developed a theoretical framework to investigate them and we collected relevant data for the wMel infection in Aedes aegypti. Using incompatibility patterns as a measure of mating success of infected versus uninfected mosquitoes, we found some evidence that uninfected males sire more offspring than infected males. However, our theoretical framework suggests that this effect is unlikely to hamper Wolbachia invasion and has only minor effects on population suppression programs. Nevertheless, we suggest that mating effects and SC need to be monitored in an ongoing manner in release programs, given the possibility of ongoing selection for altered mating patterns.

• • Ruth Nussenzweig (1928–2018) Malaria Vaccine and Immunology Pioneer

    Author: Stephen L. Hoffman

    Available online: 02 July 2018

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    In 1967 Ruth Nussenzweig and colleagues at the New York University (NYU) School of Medicine reported in Nature that mice could be protected against rodent malaria by immunization with radiation attenuated sporozoites, the malaria parasite life cycle stage that is transmitted to humans by mosquitoes. Until publication of the 1967 paper there was little to no indication or hope that humans could be completely protected against malaria. Inspired by that 1967 report, by 1974 two groups working independently, one including NYU investigators, had shown that humans could be protected by exposure to mosquitoes carrying radiation attenuated Plasmodium falciparum (Pf) sporozoites.

• • Dr. Adel A. F. Mahmoud

    Authors: Stephanie James, James W. Kazura and Daniel Colley

    Available online: 02 July 2018

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    The Society mourns the loss of famed physician-scientist and global health leader Dr. Adel Mahmoud, who died June 11, 2018, in New York City as a result of a brain hemorrhage. He is survived by his wife, Dr. Sally Hodder.

• • In Vitro Activity of Ceftolozane–Tazobactam against Burkholderia pseudomallei

    Authors: Andrew Slack, Fiona Parsonson, Katie Cronin, Kathy Engler and Robert Norton

    Available online: 25 June 2018

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    We investigated the in vitro activity of a novel fifth-generation cephalosporin–tazobactam combination, ceftolozane–tazobactam against Burkholderia pseudomallei, the etiological agent of melioidosis. Using both disc diffusion and minimum inhibitory concentration (MIC) strip techniques against 56 clinical isolates and an NCTC strain, the MIC to ceftolozane–tazobactam was found to be between 0.75 and 4 mcg/mL. The MIC50 was found to be 1.5 mcg/mL and MIC90 was 2.0 mcg/mL. This study provides initial evidence of ceftolozane–tazobactam as a novel agent in the management of melioidosis.

• • An Improved Enzyme-Linked Immunoassay for the Detection of Leptospira-Specific Antibodies

    Authors: Hua-Wei Chen, Heather Lukas, Kira Becker, Giulia Weissenberger, Eric S. Halsey, Carolina Guevara, Enrique Canal, Eric Hall, Ryan C. Maves, Drake H. Tilley, Lynn Kuo, Tadeusz J. Kochel and Wei-Mei Ching

    Available online: 25 June 2018

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    Leptospirosis is a neglected zoonotic disease with worldwide endemicity and continues to be a significant public health burden on resource-limited populations. Previously, we produced three highly purified recombinant antigens (rLipL32, rLipL41, and rLigA-Rep) and evaluated their performance of detecting Leptospira-specific antibodies in ELISA as compared with the microscopic agglutination test (MAT). The overall sensitivity of this assay approached 90%. Recently, another recombinant antigen (rLigB-Rep) was prepared. We tested each individual antigen and a 1:1:1:1 mixture of these four antigens for the detection of Leptospira-specific antibodies in ELISA. The performance of these recombinant antigens was evaluated with a much larger febrile patient panel (337 MAT-confirmed positive sera and 92 MAT-negative sera from febrile patients). Combining the detection results of immunoglobulin M and immunoglobulin G from these four individual antigens, the overall sensitivity was close to 90% but the specificity was only 66%, based on the MAT reference method. The overall sensitivity and specificity of the four-antigen mixture were 82% and 86%, respectively. The mixture of four antigens also exhibited a broader reactivity with MAT-positive samples of 18 serovars from six major pathogenic Leptospira species. Given the limitations of MAT, the data were further analyzed by Bayesian latent class model, showing that ELISA using a 1:1:1:1 mixture still maintained high sensitivity (79%) and specificity (88%) as compared with the sensitivity (90%) and specificity (83%) of MAT. Therefore, ELISA using a mixture of these four antigens could be a very useful test for seroprevalence studies.

• • Molecular Characterization of Tandem Repeat Protein 36 Gene of Ehrlichia canis Detected in Naturally Infected Dogs from Peru

    Authors: Joseph Geiger, Bridget A. Morton, Elton Jose Rosas Vasconcelos, Maryam Tngrian, Malika Kachani, Eduardo A. Barrón, Cesar M. Gavidia, Robert H. Gilman, Noelia P. Angulo, Richard Lerner, Scott Tamerin, Hannah Mirrashed, Brian Oakley and Pedro Paulo V. P. Diniz

    Available online: 25 June 2018

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    Ehrlichia spp. are emerging infectious pathogens, especially in the Americas. Although Ehrlichia canis is primarily a parasite of dogs, PCR-confirmed human infections have been reported from Mexico, Venezuela, and Costa Rica. This study reports the presence of E. canis DNA in 13.7% of 205 dogs from urban areas in Peru and of those, five were analyzed for phylogenetic variation using the Tandem Repeat Protein 36 (TRP36) gene. The use of the TRP36 gene for such analysis was validated against 16S rRNA and GroEL using Shannon’s entropy bioinformatic approach. When compared with other E. canis strains previously reported, three unique and novel E. canis strains were detected. In addition, the TRP36 amino acid tandem repeat sequences of the Peruvian strains share close similarity to an E. canis strain detected from four human blood bank samples in Costa Rica. This study reports for the first time domestic dogs infected with E. canis strains closely related to a zoonotic strain, which may be of public health concern as dogs can be chronically infected with this pathogen.

• • Experimental Infection of Rattus norvegicus by the Group II Intermediate Pathogen, Leptospira licerasiae

    Authors: Carla Fernandez, Aristea A. Lubar, Joseph M. Vinetz and Michael A. Matthias

    Available online: 25 June 2018

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    Leptospira licerasiae serovar Varillal, a group II intermediate pathogen species/serovar discovered in the Peruvian Amazon city of Iquitos, is commonly recognized in this region by sera from humans (at least 40% seroprevalence) without a known clinical history of leptospirosis. This high frequency of human seroreactivity remains unexplained. To test the hypothesis that the oral route of infection might explain the high rate of human seroreactivity against L. licerasiae, an experimental infection model using Rattus norvegicus was developed, given that rats were one of the original reservoir hosts identified as being colonized by this leptospire. Sprague–Dawley rats were experimentally exposed via mucosa, direct gastric gavage, or parenteral inoculation with nine different isolates of L. licerasiae originally isolated from Peruvian humans, peridomiciliary rodents, and wildlife. As shown by quantitative polymerase chain reaction of kidney tissue, Leptospira infection via these routes of infection was equally successful. Importantly, the data show that L. licerasiae infects R. norvegicus via the oral route demonstration, leading to renal colonization. Not only do these findings confirm the infectiousness of group II Leptospira, but also they underscore the potential importance of oral as well as mucosal and transcutaneous routes of Leptospira infection.

• • Serotype Distribution and Antimicrobial Resistance of Shigella Species in Bangui, Central African Republic, from 2002 to 2013

    Authors: Sébastien Breurec, Clotaire Rafaï, Manuella Onambele, Thierry Frank, Alain Farra, Arnaud Legrand and François-Xavier Weill

    Available online: 25 June 2018

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    Shigella is a major cause of severe diarrhea in children less than the age of 5 years in sub-Saharan Africa. The aim of this study was to describe the (sub-)serotype distribution and antimicrobial susceptibility of Shigella serogroups from Centrafrican patients with diarrhea between 2002 and 2013. We collected 443 Shigella isolates in total. The most common serogroups were Shigella flexneri (N = 243, 54.9%), followed by Shigella sonnei (N = 90, 20.3%) and Shigella dysenteriae (N = 72, 16.3%). The high diversity of (sub-)serotypes of S. flexneri and S. dysenteriae may impede the development of an efficient vaccine. Rates of resistance were high for ampicillin, chloramphenicol, tetracycline, and cotrimoxazole but low for many other antimicrobials, confirming recommendations for the use of third-generation cephalosporins (only one organism resistant) and fluoroquinolones (no resistance). However, the detection of one extended-spectrum beta-lactamase–producing Shigella organism highlights the need for continued monitoring of antimicrobial drug susceptibility.

• • Q Fever in Military Firefighters during Cadet Training in Brazil

    Authors: Elba Regina Sampaio de Lemos, Tatiana Rozental, Bibiana Nogueira Siqueira, Adonai Alvino Pessoa Júnior, Thays Euzebio Joaquim, Raphael Gomes da Silva, Carolina de Andrade Leite, Adriana Alvarez Arantes, Marisângela Ferreira da Cunha and Danielle Provençano Borghi

    Available online: 25 June 2018

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    We report five cases of Q fever among cadets during a training program for Military Firefighters Academy in the state of Rio de Janeiro, Brazil. This cluster confirms the significance of Coxiella burnetii as an infectious agent in Brazil, where the occurrence of this zoonosis is poorly documented and highlights the potential risk for Q fever transmission in rural areas or farms with infected animals.

• • Evaluation of Treatment Coverage and Enhanced Mass Drug Administration for Onchocerciasis and Lymphatic Filariasis in Five Local Government Areas Treating Twice Per Year in Edo State, Nigeria

    Authors: Emily Griswold, Abel Eigege, Cephas Ityonzughul, Emmanuel Emukah, Emmanuel S. Miri, Ifeoma Anagbogu, Yisa A. Saka, Saliu Kadiri, Solomon Adelamo, Paul Ugbadamu, Clement Ikogho and Frank O. Richards

    Available online: 25 June 2018

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    The western region of Edo state in southern Nigeria is highly endemic for onchocerciasis. Despite years of mass drug administration (MDA) with ivermectin (IVM), reports suggest persistently high prevalence of onchocerciasis, presumably because of poor coverage. In 2016, twice-per-year treatment with IVM (combined with albendazole for lymphatic filariasis in the first round where needed) began in five local government areas (LGAs) of Edo state. We undertook a multistage cluster survey within 3 months after each round of MDA to assess coverage. First-round coverage was poor: among 4,942 people of all ages interviewed from 145 clusters, coverage was 31.1% (95% confidence intervals [CI]: 24.1–38.0%). Most respondents were not offered medicines. To improve coverage in the second round, three LGAs were randomized to receive MDA through a “modified campaign” approach focused on improved supervision and monitoring. The other two LGAs continued with standard MDA as before. A similar survey was conducted after the second round, interviewing 3,362 people in 87 clusters across the five LGAs. Coverage was not statistically different from the first round (40.0% [95% CI: 31.0–49.0%]) and there was no significant difference between the groups (P = 0.7), although the standard MDA group showed improvement over round 1 (P < 0.01). The additional cost per treatment in the modified MDA was 1.6 times that of standard MDA. Compliance was excellent among those offered treatment. We concluded that poor mobilization, medicine distribution, and program penetration led to low coverage. These must be addressed to improve treatment coverage in Edo state.

• • Safety, Immunogenicity, and Protective Efficacy against Controlled Human Malaria Infection of Plasmodium falciparum Sporozoites Vaccine in Tanzanian Adults

    Authors: Said A. Jongo, Seif A. Shekalage, L. W. Preston Church, Adam J. Ruben, Tobias Schindler, Isabelle Zenklusen, Tobias Rutishauser, Julian Rothen, Anneth Tumbo, Catherine Mkindi, Maxmilian Mpina, Ali T. Mtoro, Andrew S. Ishizuka, Kassim Kamaka Ramadhani, Florence A. Milando, Munira Qassim, Omar A. Juma, Solomon Mwakasungula, Beatus Simon, Eric R. James, Yonas Abebe, Natasha K. C., Sumana Chakravarty, Elizabeth Saverino, Bakari M. Bakari, Peter F. Billingsley, Robert A. Seder, Claudia Daubenberger, B. Kim Lee Sim, Thomas L. Richie, Marcel Tanner, Salim Abdulla and Stephen L. Hoffman

    Available online: 25 June 2018

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    We are using controlled human malaria infection (CHMI) by direct venous inoculation (DVI) of cryopreserved, infectious Plasmodium falciparum (Pf) sporozoites (SPZ) (PfSPZ Challenge) to try to reduce time and costs of developing PfSPZ Vaccine to prevent malaria in Africa. Immunization with five doses at 0, 4, 8, 12, and 20 weeks of 2.7 × 105 PfSPZ of PfSPZ Vaccine gave 65% vaccine efficacy (VE) at 24 weeks against mosquito bite CHMI in U.S. adults and 52% (time to event) or 29% (proportional) VE over 24 weeks against naturally transmitted Pf in Malian adults. We assessed the identical regimen in Tanzanians for VE against PfSPZ Challenge. Twenty- to thirty-year-old men were randomized to receive five doses normal saline or PfSPZ Vaccine in a double-blind trial. Vaccine efficacy was assessed 3 and 24 weeks later. Adverse events were similar in vaccinees and controls. Antibody responses to Pf circumsporozoite protein were significantly lower than in malaria-naïve Americans, but significantly higher than in Malians. All 18 controls developed Pf parasitemia after CHMI. Four of 20 (20%) vaccinees remained uninfected after 3 week CHMI (P = 0.015 by time to event, P = 0.543 by proportional analysis) and all four (100%) were uninfected after repeat 24 week CHMI (P = 0.005 by proportional, P = 0.004 by time to event analysis). Plasmodium falciparum SPZ Vaccine was safe, well tolerated, and induced durable VE in four subjects. Controlled human malaria infection by DVI of PfSPZ Challenge appeared more stringent over 24 weeks than mosquito bite CHMI in United States or natural exposure in Malian adults, thereby providing a rigorous test of VE in Africa.

• • Water, Sanitation, and Hygiene Services in Public Health-Care Facilities in Indonesia: Adoption of World Health Organization/United Nations Children’s Fund Service Ladders to National Data Sets for a Sustainable Development Goal Baseline Assessment

    Authors: Mitsunori Odagiri, Cahyorini, Khadijah Azhar, Aidan A. Cronin, Yulian Gressando, Indah Hidayat, Widya Utami, Karina Widowati, Airin Roshita, Rooswanti Soeharno, Sonny P. Warouw and Ardhiantie

    Available online: 25 June 2018

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    Provision of basic water, sanitation, and hygiene (WASH) services in health-care facilities is gaining increased attention, given growing acceptance of its importance to the maternal and newborn quality of care agenda and the universal health coverage framework. Adopting and contextualizing an emerging World Health Organization/United Nations Children’s Fund Joint Program Monitoring service ladder approach to national data collected in 2010/2011, we estimated the national coverage of primary health centers (PHCs) (N = 8,831), auxiliary PHCs (N = 22,853), village health posts (N = 28,692), and village maternity clinics (N = 14,396) with basic WASH services in Indonesia as part of a Sustainable Development Goal baseline assessment. One quarter of PHCs did not have access to a combination of basic water and sanitation (WatSan) services (23.6%) with significant regional variation (10.6–59.8%), whereas more than two-third of PHCs (72%) lacked handwashing facility with soap in all three locations (general consulting room, immunization room, and delivery room). More than a half of the three lower health service level facility types lacked basic WatSan services. National health facility monitoring systems need to be urgently strengthened for tracking the progress and addressing gaps in basic WASH services in health facilities in Indonesia.

• • Case Report: Fulminant Murine Typhus Presenting with Status Epilepticus and Multi-Organ Failure; an Autopsy Case and a Review of the Neurologic Presentations of Murine Typhus

    Authors: Benjamin E. Stephens, Meilinh Thi, Rahaf Alkhateb, Apeksha Agarwal, Francis E. Sharkey, Christopher Dayton and Gregory M. Anstead

    Available online: 25 June 2018

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    Murine typhus (MT) is an important cause of febrile illness in endemic areas, and there is an epidemiologic resurgence of this infection currently transpiring in Texas and California. Fatal cases and severe neurological complications are rare. A fatal case of MT in a middle-aged man is reported with a course culminating in multi-organ failure and refractory status epilepticus. An autopsy revealed hemorrhagic pneumonia, acute tubular necrosis, and ischemic necrosis in the liver, adrenals, and brain. We have also reviewed the neurologic complications of MT.

• • Mixed Infection with Severe Fever with Thrombocytopenia Syndrome Virus and Two Genotypes of Scrub Typhus in a Patient, South Korea, 2017

    Authors: Jeong Rae Yoo, Sang Taek Heo, Ji-Hoon Kang, Dahee Park, Jeong Soon Kim, Jeong Hoon Bae, Jong Jin Woo, Suhyun Kim and Keun Hwa Lee

    Available online: 25 June 2018

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    Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease with a high mortality rate. Infection can also occur through close contact with an infected patient. Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi, a bacterium transmitted to humans through chigger mite bites. South Korea is an endemic region of SFTS and scrub typhus. In this study, we confirmed that a patient was coinfected with SFTS virus and two (Boryong and Taguchi) genotypes of O. tsutsugamushi.

• • Associations between Use of Antimalarial Medications and Health among U.S. Veterans of the Wars in Iraq and Afghanistan

    Authors: Aaron I. Schneiderman, Yasmin S. Cypel, Erin K. Dursa and Robert Bossarte

    Available online: 25 June 2018

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    Mefloquine (Lariam®) has been linked to acute neuropsychiatric side effects. This is a concern for U.S. veterans who may have used mefloquine during recent Southwest Asia deployments. Using data from the National Health Study for a New Generation of U.S. Veterans, a population-based study of U.S. veterans who served between 2001 and 2008, we investigated associations between self-reported use of antimalarial medications and overall physical and mental health (MH) using the twelve-item short form, and with other MH outcomes using the post-traumatic stress disorder Checklist-17 and the Patient Health Questionnaire (anxiety, major depression, and self-harm). Multivariable logistic regression was performed to examine associations between health measures and seven antimalarial drug categories: any antimalarial, mefloquine, chloroquine, doxycycline, primaquine, mefloquine plus any other antimalarial, and any other antimalarial or antimalarial combination while adjusting for the effects of deployment and combat exposure. Data from 19,487 veterans showed that although antimalarial use was generally associated with higher odds of negative health outcomes, once deployment and combat exposure were added to the multivariable models, the associations with each of the MH outcomes became attenuated. A positive trend was observed between combat exposure intensity and prevalence of the five MH outcomes. No significant associations were found between mefloquine and MH measures. These data suggest that the poor physical and MH outcomes reported in this study population are largely because of combat deployment exposure.

• • Efficacy of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum Malaria in Under-Five-Year-Old Nigerian Children Ten Years Following Adoption as First-Line Antimalarials

    Authors: Joy C. Ebenebe, Godwin Ntadom, Jose Ambe, Robinson Wammanda, Nma Jiya, Finomo Finomo, George Emechebe, Olugbenga Mokuolu, Kazeem Akano, Chimere Agomo, Onikepe A. Folarin, Stephen Oguche, Francis Useh, Wellington Oyibo, Temitope Aderoyeje, Mohammed Abdulkadir, Nnenna M. Ezeigwe, Christian Happi, Akintunde Sowunmi and for the Antimalarial Therapeutic Efficacy Monitoring Group, National Malaria Elimination Programme, The Federal Ministry of Health, Abuja, Nigeria

    Available online: 25 June 2018

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    The efficacies of 3-day regimens of artemether–lumefantrine (AL), artesunate–amodiaquine (AA), and dihydroartemisinin–piperaquine (DHP) were evaluated in 910 children < 5 years old with uncomplicated malaria from six geographical areas of Nigeria. Parasite positivity 1 day and Kaplan–Meier estimated risk of persistent parasitemia 3 days after therapy initiation were both significantly higher, and geometric mean parasite reduction ratio 1 day after treatment initiation (PRRD1) was significantly lower in AL-treated children than in AA- and DHP-treated children. No history of fever, temperature > 38°C, enrollment parasitemia > 75,000 μL−1, and PRRD1 < 5,000 independently predicted persistent parasitemia 1 day after treatment initiation. Parasite clearance was significantly faster and risk of reappearance of asexual parasitemia after initial clearance was significantly lower in DHP-treated children. Overall, day 42 polymerase chain reaction–corrected efficacy was 98.3% (95% confidence interval [CI]: 96.1–100) and was similar for all treatments. In a non-compartment model, declines of parasitemias were monoexponential with mean terminal elimination half-life of 1.3 hours and unimodal frequency distribution of half-lives. All treatments were well tolerated. In summary, all three treatments evaluated remain efficacious treatments of uncomplicated malaria in young Nigerian children, but DHP appears more efficacious than AL or AA.

• • Human Strongyloidiasis in Hawaii: A Retrospective Review of Enzyme-Linked Immunosorbent Assay Serodiagnostic Testing

    Authors: Matthew Akiyama and Joel D. Brown

    Available online: 25 June 2018

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    Human strongyloidiasis is widely prevalent in tropical and subtropical regions worldwide but is not endemic in Hawaii. Subclinical, chronic infections may be lifelong; immunosuppressive therapy, particularly with glucocorticoids, may lead to serious or fatal disseminated disease, which is preventable. We performed a retrospective analysis of patients tested for Strongyloides IgG antibody in an academic medical center in Honolulu, Hawaii, from 2005 to 2012. Of the 475 patients tested, 78 (16%) were seropositive. The largest proportion of seropositive cases was found among Micronesians (30%), Polynesians (26%), Filipinos (13%), and Southeast Asians (11%). Among the seropositive patients, the most likely reason for clinicians to order testing was blood eosinophilia. Stool parasite examination results were available for 58% of seropositive patients of which 11% were positive for Strongyloides stercoralis larvae. Antihelminthic therapy, usually ivermectin, was ordered for 70% of patients. After treatment, blood eosinophilia and Strongyloides serology results were reassessed for 79% and 24% of patients, respectively; both tests tended to show improvement. Travelers and immigrants from Strongyloides-endemic areas, including Micronesia and Polynesia, should have serodiagnostic testing for latent strongyloidiasis, and if positive, treated empirically with ivermectin, particularly when corticosteroids or other immunosuppressive therapy are anticipated.

• • Development of Loop-Mediated Isothermal Amplification–Based Lateral Flow Device Method for the Detection of Malaria

    Authors: Prudhvi Chand Mallepaddi, Meng-Yee Lai, Sudhakar Podha, Choo-Huck Ooi, Jonathan Wee-Kent Liew, Rathnagiri Polavarapu and Yee-Ling Lau

    Available online: 25 June 2018

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    The present study aims to develop a method for rapid diagnosis of malaria using loop-mediated isothermal amplification (LAMP) combined with a lateral flow device (LFD). By adding the biotin-labeled and FAM-labeled loop primers to the LAMP reaction solution, the end product can be visualized on a lateral flow dipstick. The entire procedure takes approximately 42 minutes to complete, LAMP assay exhibited high sensitivity, as the detection limit was 0.01 pg/μL for all five Plasmodium species. It was demonstrated that all Plasmodium knowlesi (N = 90) and Plasmodium vivax (N = 56) were positively amplified by LAMP-LFD assay, whereas healthy donor samples (N = 8) were negative. However, not all mixed infections were positive, and other infected nonmalaria samples were negative. Loop-mediated isothermal amplification-LFD represents a robust approach with potential suitability for use in resource-constrained laboratories. We believe that LAMP-LFD has a potential to be developed as point-of-care diagnostic tool in future.

• • Iron Deficiency is Prevalent among HIV-Infected Kenyan Adults and is Better Measured by Soluble Transferrin Receptor than Ferritin

    Authors: Anne E. P. Frosch, George Ayodo, Eliud O. Odhiambo, Kathleen Ireland, John Vulule and Sarah E. Cusick

    Available online: 25 June 2018

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    Iron deficiency (ID) and HIV infection frequently coexist. Little data exist on ID in HIV-infected individuals, partly because the iron marker ferritin is altered by inflammation common in HIV infection. We measured iron biomarkers (ferritin, soluble transferrin receptor [sTfR], hepcidin) and red cell indices (hemoglobin, mean cell volume [MCV]) in newly diagnosed, ART-naive, HIV-infected (N = 138) and uninfected (N = 52) Kenyan adults enrolled in a study of the immune response to malaria. We compared markers between infected and uninfected groups with t test and Wilcoxon Rank–Sum, used Spearman correlation to determine the association between iron and inflammatory markers, and applied logistic regression to determine which markers best predicted anemia. HIV-infected individuals had lower hemoglobin (P < 0.001), lower MCV (P < 0.001), higher sTfR (P = 0.003), and a greater prevalence of ID (sTfR > 8.3 mg/L) than uninfected individuals. Ferritin was elevated in HIV-infected individuals and was more strongly correlated with C-reactive protein (ρ = 0.43, P < 0.001) and hepcidin (ρ = 0.69, P < 0.001) than with hemoglobin. The best predictor of anemia in HIV-infected participants was sTfR, with a one log-unit increase in sTfR associated with a 6-fold increase in the odds of anemia (odds ratio = 6.3, 95% confidence interval: 1.8–21.8). These data suggest a significant burden of ID among treatment-naive HIV-infected Kenyan adults. Soluble transferrin receptor may be a reliable marker of ID in HIV-mediated inflammation.

• • Protobothrops mucrosquamatus Bites to the Head: Clinical Spectrum from Case Series

    Authors: Ying-Tse Yeh, Min-Hui Chen, Julia Chia-Yu Chang, Ju-Sing Fan, David Hung-Tsang Yen and Yen-Chia Chen

    Available online: 25 June 2018

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    Protobothrops mucrosquamatus (Trimeresurus mucrosquamatus) is a medically important species of pit viper with a wide geographic distribution in Southeast Asia. Bites by P. mucrosquamatus mostly involve the extremities. Little is known about the toxic effects of P. mucrosquamatus envenoming to the head because of the infrequency of such occurrence. To better delineate the clinical manifestations of envenoming to the head, we report three patients who suffered from P. mucrosquamatus bites to the head and were treated successfully. All three patients developed progressive soft tissue swelling extending from head to neck, with two patients expanding further onto the anterior chest wall. Mild thrombocytopenia was noted in two patients. One patient had transient acute renal impairment and airway obstruction, necessitating emergent intubation. All three patients received high doses of species-specific antivenom with recovery within 1 week. No adverse reactions to antivenom were observed.

• • Zika Virus and the World Health Organization Criteria for Determining Recent Infection Using Plaque Reduction Neutralization Testing

    Authors: Matthew J. Ward, Jackeline Alger, Mabel Berrueta, Harry Bock, Pierre Buekens, Maria Luisa Cafferata, Alvaro Ciganda, Jorge García, Kimberly García, Ivette Lorenzana, Wendy Lopez, Leda Parham and Dawn M. Wesson

    Available online: 25 June 2018

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    The recent Zika virus (ZIKV) epidemic swept across Latin America and the Caribbean, where dengue virus (DENV) is endemic. The antigenic similarities of these closely related flaviviruses left researchers and clinicians with challenges to interpret serological tests. Thirty-six women attending a prenatal clinic in Honduras and with positive DENV IgM enzyme-linked immunoabsorbent assays (ELISAs) were screened with a ZIKV IgM ELISA, RT-PCR for ZIKV and DENV 1–4, and plaque reduction neutralization tests (PRNTs) for ZIKV and DENV-2. Plaque reduction neutralization test results were interpreted using the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Using the WHO criteria of a PRNT90 titer ≥ 20 and a 4-fold difference between ZIKV and DENV titers, we determined that 69.4% of samples had a recent ZIKV infection, compared with 5.6% using CDC criteria. The interpretation of ZIKV PRNTs in a DENV-endemic region is highly dependent on the choice of interpretation criteria.

• • Calcified Neurocysticercosis and Headache in an Endemic Village: A Case–Control Study Nested to a Population-Based Cohort

    Authors: Oscar H. Del Brutto, Ana M. Robles, Robertino M. Mera, Aldo F. Costa, Elizabeth Darsan, Lucía Milla, Jessica Montes, Julio Lama, Victor J. Del Brutto, Mauricio Zambrano and Mark J. Sedler

    Available online: 25 June 2018

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    Headache in patients with calcified neurocysticercosis (NCC) is probably common but has been largely overlooked. We aimed to assess the presence, characteristics, and diagnosis of headache across patients with calcified NCC and their matched controls. In this case–control study nested to a population-based cohort, Atahualpa residents aged ≥ 20 years with calcified NCC were identified as case patients and paired 1:1 to age- and gender-matched randomly selected controls. A culturally adapted questionnaire was derived from the EUROLIGHT. Headache diagnosis was established according to the International Classification of Headache Disorders, 3rd edition. Conditional logistic regression models for matched paired data were fitted to assess the independent association between calcified NCC (as the exposure) and headache variables, after adjusting for education, alcohol intake, depression, and epilepsy. The selection process generated 106 case patients and their matched controls. Lifetime headache prevalence (OR: 4.18; 95% Confidence Interval [CI]: 1.79–9.75; P = 0.001), current headaches (OR: 4.19; 95% CI: 1.92–9.16; P < 0.001), and intense headaches (OR: 9.47; 95% CI: 2.88–31.19; P < 0.001) were more frequent among cases than in controls. In addition, migraine (but not other forms of headache) was more frequent among subjects with calcified NCC (OR: 4.89; 95% CI: 2.36–11.39; P < 0.001). This study shows a robust epidemiological association between headache—particularly migraine—and calcified NCC.

• • How Far Are We from Reaching Universal Malaria Testing of All Fever Cases?

    Authors: Mateusz M. Plucinski, Timothée Guilavogui, Alioune Camara, Médoune Ndiop, Moustapha Cisse, John Painter and Julie Thwing

    Available online: 25 June 2018

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    Universal malaria diagnostic testing of all fever cases is the first step in correct malaria case management. However, monitoring adherence to universal testing is complicated by unreliable recording and reporting of the true number of fever cases. We searched the literature to obtain gold-standard estimates for the proportion of patients attending outpatient clinics in sub-Saharan Africa with malarial and non-malarial febrile illness. To correct for differences in malaria transmission, we calculated the proportion of patients with fever after excluding confirmed malaria cases. Next, we analyzed routine data from Guinea and Senegal to calculate the proportion of outpatients tested after exclusion of confirmed malaria cases from the numerator and denominator. From 12 health facility surveys in sub-Saharan Africa with gold-standard fever screening, the median proportion of febrile illness among outpatients after exclusion of confirmed malaria fevers was 57% (range: 46–80%). Analysis of routine data after exclusion of confirmed malaria cases demonstrated much lower testing proportions of 23% (Guinea) and 13% (Senegal). There was substantial spatial and temporal heterogeneity in this testing proportion, and testing in Senegal was correlated with malaria season. Given the evidence from gold-standard surveys that at least 50% of non-malaria consultations in sub-Saharan Africa are for febrile illness, it appears that a substantial proportion of patients with fever are not tested for malaria in health facilities when considering routine data. Tracking the proportion of patients tested for malaria after exclusion of the confirmed malaria cases could allow programs to make inferences about malaria testing practices using routine data.

• • A Pilot Study to Assess Safety and Feasibility of Intrathecal Immunoglobulin for the Treatment of Adults with Tetanus

    Authors: Huynh Thi Loan, Lam Minh Yen, Evelyne Kestelyn, Nguyen Van Hao, Nguyen Thi Hoang Mai, Duong Bich Thuy, Ha Thi Hai Duong, Nguyen Thi Phuong Dung, Nguyen Hoan Phu, Pham Thi Lieu, Tran Tan Thanh, Ronald Geskus, H. Rogier van Doorn, Le Van Tan, Duncan Wyncoll, Nicholas P. J. Day, Tran Tinh Hien, Guy E. Thwaites, Nguyen Van Vinh Chau and C. Louise Thwaites

    Available online: 18 June 2018

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    Tetanus remains a significant burden in many low- and middle-income countries. The tetanus toxin acts within the central nervous system and intrathecal antitoxin administration may be beneficial, but there are safety concerns, especially in resource-limited settings. We performed a pilot study to assess the safety and feasibility of intrathecal human tetanus immunoglobulin in five adults with tetanus before the conduct of a large randomized controlled trial. Intrathecal injection via lumbar puncture was given to all patients within a median 140 (range 100–165) minutes of intensive care unit (ICU) admission. There were no serious adverse effects associated with the procedure although three patients had probably related minor adverse events which resolved spontaneously. Median ICU length of stay was 14 (range 5–17) days. Two patients required mechanical ventilation and one developed a deep vein thrombosis. Within 240 days of hospital discharge, no patients died and all patients returned to work.

• • Acceptability and Feasibility of Sharing a Soapy Water System for Handwashing in a Low-Income Urban Community in Dhaka, Bangladesh: A Qualitative Study

    Authors: Farhana Sultana, Leanne E. Unicomb, Fosiul A. Nizame, Notan Chandra Dutta, Pavani K. Ram, Stephen P. Luby and Peter J. Winch

    Available online: 11 June 2018

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    Handwashing with soap at key times is an effective means of reducing pathogen transmission. In a low-income community in urban Dhaka, we piloted and evaluated the acceptability and feasibility of a shared handwashing intervention. This included promotion by community health promoters of a homemade solution of detergent powder mixed with water and stored in a 1.5-L reclaimed mineral water bottle. Community health promoters encouraged sharing of the recurrent detergent cost among compound members. Of 152 participating compounds, fieldworkers randomly selected 60 for qualitative assessment. Fieldworkers conducted 30 in-depth interviews and five focus group discussions among purposively selected compound members. The reclaimed bottles served as an easily accessible dispenser for the soapy water, which could feasibly be retained next to the toilet and kitchen areas for communal use. Bottles functioned as a positive reminder for handwashing at recommended key times. Most compounds (45/60, 75%) shared a common soapy water system and its associated costs. There was reluctance to prepare soapy water for shared use in the remaining 25%. Soapy water was an acceptable hand cleaning agent, with the bottle as a feasible dispenser. It was simple in design, cost-effective, replicable, popular with intervention recipient, and neighboring nonrecipients, and commonly shared among nonrelated households. The need to share expenses and product preparation served as a barrier. Developing a sustainable maintenance system, therefore, is critical to ensuring the public health benefits of handwashing with soap.

• • Toward Point-of-Care Drug Quality Assurance in Developing Countries: Comparison of Liquid Chromatography and Infrared Spectroscopy Quantitation of a Small-Scale Random Sample of Amoxicillin

    Authors: Norah Alotaibi, Sean Overton, Sharon Curtis, Jason W. Nickerson, Amir Attaran, Sheldon Gilmer and Paul M. Mayer

    Available online: 11 June 2018

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    Substandard antibiotics are thought to be a major threat to public health in developing countries and a cause of antimicrobial resistance. However, assessing quality outside of a laboratory setting, using simple equipment, is challenging. The aim of this study was to validate the use of a portable Fourier transform infrared (FT-IR) spectrometer for the identification of substandard antibiotics. Results are presented for amoxicillin packages from Haiti, Ghana, Sierra Leone, Democratic Republic of Congo, India, Papua New Guinea, and Ethiopia collected over the course of 6 months in 2017, including two field trips with the FT-IR to Ghana and Sierra Leone. Canadian samples were used as a control. Regarding drug quality, of 290 individual capsules of amoxicillin analyzed, 13 were found to be substandard with total active pharmaceutical ingredients (API) lying outside the acceptable range of 90–110%. Of these 13, four were below 80% API. The FT-IR reliably identified these outliers and was found to yield results in good agreement with the established pharmacopeia liquid chromatography protocol. We conclude that the portable FT-IR may be suitable to intercept substandard antibiotics in developing countries where more sophisticated techniques are not readily available.

• • An Evolving Choice in a Diverse Water Market: A Quality Comparison of Sachet Water with Community and Household Water Sources in Ghana

    Authors: Danice Guzmán and Justin Stoler

    Available online: 11 June 2018

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    Packaged water, particularly bagged sachet water, has become an important drinking water source in West Africa as local governments struggle to provide safe drinking water supplies. In Ghana, sachet water has become an important primary water source in urban centers, and a growing literature has explored various dimensions of this industry, including product quality. There is very little data on sachet water quality outside of large urban centers, where smaller markets often mean less producer competition and less government regulation. This study analyzes the microbiological quality of sachet water alongside samples of other common water sources at point-of-collection (POC) and point-of-use (POU) in 42 rural, peri-urban, and small-town Ghanaian communities using the IDEXX Colilert® 18. Levels of coliform bacteria and Escherichia coli detected in sachet water samples were statistically and significantly lower than levels detected in all other water sources at POU, including public taps and standpipes, and statistically similar or significantly lower at POC. In diverse waterscapes where households regularly patch together their water supply from different sources, sachet water appears to be an evolving alternative for safe drinking water despite many caveats, including higher unit costs and limited opportunities to recycle the plastic packaging.

• • Effective Population Size Differences in Calomys musculinus, the Host of Junín Virus: Its Relationship with the Epidemiological History of Argentine Hemorrhagic Fever

    Authors: Marina B. Chiappero, María Florencia Piacenza, María Cecilia Provensal, Gladys E. Calderón, Cristina N. Gardenal and Jaime J. Polop

    Available online: 11 June 2018

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    Argentine hemorrhagic fever (AHF) is a serious endemic disease in Argentina, produced by Junín virus, whose host is the Sigmodontinae rodent Calomys musculinus. Within the endemic area, human incidence and proportion of infected rodents remains high for 5–10 years after the first appearance of the disease (epidemic [E] zone) and then gradually declines to sporadic cases (historic [H] zone). We tested the hypothesis that host populations within the E zone are large and well connected by gene flow, facilitating the transmission and maintenance of the virus, whereas those in the H and nonendemic (NE) zones are small and isolated, with the opposite effect. We estimated parameters affected by levels of gene flow and population size in 14 populations of C. musculinus: population effective size (N e), genetic variability, and mean relatedness. Our hypothesis was not supported: the lowest levels of variability and of N e and the highest genetic relatedness among individuals were found in the H zone. Populations from the NE zone displayed opposite results, whereas those in the E zone showed intermediate values. If we consider that populations are first NE, then E, and finally H, a correlative decrease in N e was observed. Chronically infected females have a low reproductive success. We propose that this would lower N e because each cohort would originate from a fraction of females of the previous generation, and affect other factors such as proportion of individuals that develop acute infection, probability of viral transmission, and evolution of virulence, which would explain, at least partly, the changing incidence of AHF.

• • Carotid Taenia solium Oncosphere Infection: A Novel Porcine Neurocysticercosis Model

    Authors: Karen A. Alroy, Gianfranco Arroyo, Robert H. Gilman, Eloy Gonzales-Gustavson, Linda Gallegos, Cesar M. Gavidia, Manuela Verastegui, Silvia Rodriguez, Teresa Lopez, Luis A. Gomez-Puerta, Joseph Alroy, Hector H. Garcia, Armando E. Gonzalez and for the Cysticercosis Working Group in Peru

    Available online: 11 June 2018

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    Neurocysticercosis (NCC), the infection of the human central nervous system (CNS) with larval cysts of Taenia solium causes widespread neurological morbidity. Animal models are crucial for studying the pathophysiology and treatment of NCC. Some drawbacks of current NCC models include differences in the pathogenesis of the model and wild-type parasite, low rates of infection efficiency and lack of reproducibility. We describe a novel porcine model that recreates infection in the CNS with high efficiency. Activated oncospheres, either in a high (45,000–50,000) or low (10,000) dose were inoculated in the common carotid artery of 12 pigs by ultrasound-guided catheterization. Following oncosphere injection, either a high (30 mL) or low (1–3 mL) volume of saline flush was also administered. Cyst burden in the CNS was evaluated independently according to oncosphere dose and flush volume. Neurocysticercosis was achieved in 8/12 (66.7%) pigs. Cyst burden in the CNS of pigs was higher in the high versus the low oncosphere dose category (median: 4.5; interquartile ranges [IQR]: 1–8 and median: 1; IQR: 0–4, respectively) and in the high versus the low flush volume category (median 5.5; IQR: 1–8 and median: 1; IQR: 0–2, respectively), although not statistically different. All cysts in the CNS were viable, whereas both viable and degenerated cysts were found in the musculature. Carotid injection of activated oncospheres in pigs is effective in reproducing NCC. Oncosphere entry into the CNS by way of vasculature mimics wild-type infection, and provides a useful alternative for future investigations on the pathogenesis and antiparasitic treatment of NCC.

• • Retinal Parameters as Compared with Head Circumference, Height, Weight, and Body Mass Index in Children in Kenya and Bhutan

    Authors: Sara J. Grundy, Lhab Tshering, Stanley W. Wanjala, Megan B. Diamond, Martin S. Audi, Sashank Prasad, Russell T. Shinohara, Debora Rogo, Dechen Wangmo, Ugyen Wangdi, Abi Aarayang, Thukten Tshering, Thomas F. Burke and Farrah J. Mateen

    Available online: 11 June 2018

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    The retina shares embryological derivation with the brain and may provide a new measurement of overall growth status, especially useful in resource-limited settings. Optical coherence tomography (OCT) provides detailed quantification of retinal structures. We enrolled community-dwelling children ages 3–11 years old in Siaya, Kenya and Thimphu, Bhutan in 2016. We measured head circumference (age < 5 years only), height, and weight, and standardized these by age and gender. Research staff performed OCT (iScan; Optovue, Inc., Fremont, CA), measuring the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) thicknesses. A neuro-ophthalmologist performed quality control for centration, motion artifact, and algorithm-derived quality scores. Generalized estimating equations were used to determine the relationship between anthropometric and retinal measurements. Two hundred and fifty-eight children (139 females, average age 6.4 years) successfully completed at least one retinal scan, totaling 1,048 scans. Nine hundred and twenty-two scans (88.0%) were deemed usable. Fifty-three of the 258 children (20.5%) were able to complete all six scans. Kenyan children had a thinner average GCC (P < 0.001) than Bhutanese children after adjustment for age and gender, but not RNFL (P = 0.70). In models adjusting for age, gender, and study location, none of standardized height, weight, and body mass index (BMI) were statistically significantly associated with RNFL or GCC. We determined that OCT is feasible in some children in resource-limited settings, particularly those > 4 years old, using the iScan device. We found no evidence for GCC or RNFL as a proxy for height-, weight-, or BMI-for-age. The variation in mean GCC thickness in Asian versus African children warrants further investigation.

• • Utilization and Clinical Value of Diagnostic Modalities for Tuberculosis in a High HIV Prevalence Setting

    Authors: Stephanie Gati, Rhoda Chetty, Douglas Wilson and Jacqueline M. Achkar

    Available online: 11 June 2018

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    Human immunodeficiency virus (HIV) infection is a major risk factor for the development of active tuberculosis (TB), one of the deadliest infectious diseases globally. The high mortality associated with the disease can be reduced by early diagnosis and prompt antituberculous treatment initiation. Facilities in TB-endemic regions are increasing the use of nucleic acid amplification (e.g., GeneXpert), which provides rapid results but may have suboptimal sensitivity in HIV-associated TB. Our objective was to evaluate the current practices for TB diagnosis at Edendale Hospital, a large regional hospital in KwaZulu-Natal, South Africa—a TB-endemic region with high HIV prevalence. In this cross-sectional study, all adult inpatients newly started on TB treatment at Edendale were identified over a 6-week period. Demographics, clinical information, diagnostic test results, and outcomes were documented. Pulmonary TB (PTB), extrapulmonary TB (EXTB), and PTB + EXTB were defined as disease evidence in the lungs, other organs, or both, respectively. Ninety-four cases were identified, of which 83% were HIV-associated. Only 30% of all TB patients were microbiologically confirmed, consisting of 7/16 (44%) HIV-uninfected and 21/78 (27%) HIV-infected TB patients. Smear microscopy and mycobacterial culture were seldom ordered. Ultrasound was performed in about one-third of suspected EXTB cases and was valuable in identifying abdominal TB. In this clinical setting with a high incidence of HIV-associated TB, TB diagnosis was more commonly based on clinical assessment and imaging results than on mycobacterial gold standard test confirmation.

• • Association of Fecal Markers of Environmental Enteric Dysfunction with Zinc and Iron Status among Children at First Two Years of Life in Bangladesh

    Authors: Shah Mohammad Fahim, Subhasish Das, Kazi Istiaque Sanin, Md. Amran Gazi, Mustafa Mahfuz, M. Munirul Islam and Tahmeed Ahmed

    Available online: 11 June 2018

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    Environmental enteric dysfunction (EED) causes gut inflammation and increased intestinal permeability leading to deficiencies in micronutrients such as zinc and iron. Fecal markers such as myeloperoxidase (MPO), neopterin (NEO), and alpha-1-anti-trypsin (AAT) can predict EED. The aim of this study was to examine the association between fecal markers of EED with zinc and iron status among children at first 2 years of life. Malnutrition and Enteric Disease Study Bangladeshi birth cohort data were used to conduct this analysis. Multivariable analyses using generalized estimating equations were performed to test the association between individual fecal markers with zinc or iron status of the children. A total of 265 children were enrolled in the study (male:female = 1:1). Of the 627 stool samples collected (N = 222 children), 535, 511, and 577 were accompanied by zinc, ferritin, and soluble transferrin receptor values, respectively. Median (interquartile range [IQR]) values of AAT, MPO, and NEO were 0.33 (0.18–0.62) mg/g, 3,895.42 (1,563.76–8,432.82) ng/mL, and 890.81 (331.57–2,089.04) nmol/L, respectively. Overall, 60%, 71%, and 97% of samples were above the values considered normal in nontropical settings for AAT, MPO, and NEO, respectively. High AAT levels were significantly associated with low ferritin values after adjusting for age and gender (coefficient = −5.85; 95% confidence interval = −11.23 to −0.47; P value = 0.03). No such association was found between AAT and plasma zinc status. Myeloperoxidase and NEO were not associated with plasma zinc or iron status. The study results imply the importance of enteric protein loss in contributing to reduced ferritin levels at first 2 years of life.

• • Schistosoma mansoni Mass Drug Administration Regimens and Their Effect on Morbidity among Schoolchildren over a 5-Year Period—Kenya, 2010–2015

    Authors: Anita D. Sircar, Pauline N. M. Mwinzi, Isaac O. Onkanga, Ryan E. Wiegand, Susan P. Montgomery and W. Evan Secor

    Available online: 11 June 2018

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    Schistosomiasis control programs are designed to reduce morbidity by providing mass drug administration (MDA) of praziquantel to at-risk populations. We compared morbidity markers between two cohorts of Kenyan schoolchildren that initially had high prevalence of Schistosoma mansoni infections. One cohort (N = 416 at year 1) received four rounds of annual MDA in a community-wide treatment (CWT) strategy. The other cohort (N = 386 at year 1) received school-based treatment (SBT) every other year over the 4-year period. We measured infection with S. mansoni and soil-transmitted helminths (STH) as well as subtle morbidity markers at year 1, year 3, and year 5 and compared cohorts with mixed models after controlling for age and gender. At year 5, neither overall S. mansoni prevalence nor the prevalence of high infection–intensity S. mansoni infection was significantly reduced compared with baseline in either the CWT cohort (N = 277 remaining) or the SBT cohort (N = 235 remaining). Nevertheless, by year 5, children in both cohorts demonstrated significant decreases in wasting, ultrasound-detected organomegaly, and STH infection along with significantly improved pediatric quality-of-life scores compared with year 1. Stunting did not change over time, but children who were S. mansoni egg–positive at year 5 had significantly more stunting than children without schistosomiasis. The only significant difference between arms at year 5 was a lower prevalence of STH infections in the CWT group.

• • Genetic Characterization of the Patois Serogroup (Genus Orthobunyavirus; Family Peribunyaviridae) and Evidence That Estero Real Virus is a Member of the Genus Orthonairovirus

    Authors: Patricia V. Aguilar, William Marciel de Souza, Jesus A. Silvas, Thomas Wood, Steven Widen, Marcílio Jorge Fumagalli and Márcio Roberto Teixeira Nunes

    Available online: 11 June 2018

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    Estero Real virus (ERV) was isolated in 1980 from Ornithodoros tadaridae ticks collected in El Estero Real, Sancti Spiritus, Cuba. Antigenic characterization of the isolate based on serological methods found a relationship with Abras and Zegla viruses and, consequently, the virus was classified taxonomically within the Patois serogroup. Given the fact that genetic characterization of Patois serogroup viruses has not yet been reported and that ERV is the only virus within the Patois serogroup isolated from ticks, we recently conducted nearly complete genome sequencing in an attempt to gain further insight into the genetic relationship of ERV with other Patois serogroup viruses and members of Peribunyaviridae family (Bunyavirales order). With the exception of ERV, our sequencing and phylogenetic studies revealed the close relationship of the Patois serogroup viruses to each other, forming a clear divergent clade from other members of the Orthobunyavirus genus (Peribunyaviridae family). Notably, our analysis also revealed that ERV forms a monophyletic clade that is closely related to species of the Orthonairovirus genus (Nairoviridae family) in all the genome segments. In light of these findings, we believe that the taxonomic classification of ERV should be revised.

• • Parallel Decline of Malaria and Rickettsia felis Infections in Senegal

    Authors: Oleg Mediannikov, Cedric Abat, Cheikh Sokhna and Didier Raoult

    Available online: 04 June 2018

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    Rickettsia felis is a common emerging pathogen in sub-Saharan Africa. Comparing dynamics of morbidities due to malaria and R. felis infections in two Senegalese villages, we found a strong and significant correlation between them. Malaria morbidity is strongly decreasing because of the implementation of long-lasting insecticidal nets, so we hypothesize that the same measure may decrease the R. felis infections.

• • Urban Rodent Surveillance, Climatic Association, and Genomic Characterization of Seoul Virus Collected at U.S. Army Garrison, Seoul, Republic of Korea, 2006–2010

    Authors: Heung-Chul Kim, Won-Keun Kim, Jin Sun No, Seung-Ho Lee, Se Hun Gu, Sung-Tae Chong, Terry A. Klein and Jin-Won Song

    Available online: 04 June 2018

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    Rodent-borne pathogens pose a critical public health threat in urban areas. An epidemiological survey of urban rodents was conducted from 2006 to 2010 at the U.S. Army Garrison (USAG), Seoul, Republic of Korea (ROK), to determine the prevalence of Seoul virus (SEOV), a rodent-borne hantavirus. A total of 1,950 rodents were captured at USAG, Yongsan, near/in 19.4% (234/1,206) of the numbered buildings. Annual mean rodent infestation rates were the highest for food service facilities, e.g., the Dragon Hill Lodge complex (38.0 rodents) and the Hartell House (18.8 rodents). The brown rat, Rattus norvegicus, accounted for 99.4% (1,939/1,950) of all the rodents captured in the urban area, whereas only 0.6% (11/1,950) of the rodents was house mice (Mus musculus). In November 2006, higher numbers of rats captured were likely associated with climatic factors, e.g., rainfall and temperatures as rats sought harborage in and around buildings. Only 4.7% (34/718) rodents assayed for hantaviruses was serologically positive for SEOV. A total of 8.8% (3/34) R. norvegicus were positive for SEOV RNA by RT-PCR, of which two SEOV strains were completely sequenced and characterized. The 3′ and 5′ terminal sequences revealed incomplete complementary genomic configuration. Seoul virus strains Rn10-134 and Rn10-145 formed a monophyletic lineage with the prototype SEOV strain 80-39. Seoul virus Medium segment showed the highest evolutionary rates compared with the Large and Small segments. In conclusion, this report provides significant insights into continued rodent-borne disease surveillance programs that identify hantaviruses for analysis of disease risk assessments and development of mitigation strategies.

• • Rickettsial Infections among Cats and Cat Fleas in Riverside County, California

    Authors: Kristin E. Mullins, Alice N. Maina, Laura Krueger, Ju Jiang, Robert Cummings, Allan Drusys, Greg Williams, Major Dhillon and Allen L. Richards

    Available online: 04 June 2018

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    Presently, few studies have investigated the role of domestic cats (Felis catus) in the recrudescence of flea-borne rickettsioses in California and the southern United States. In this study, we aimed to investigate the presence of Rickettsia typhi or Rickettisa felis in domestic cats (F. catus) and the fleas (primarily Ctenocephalides felis, the cat flea) associated with these cats in Riverside County, California. Thirty cats and 64 pools of fleas collected from these cats were investigated for rickettsial infections. Three cats and 17 flea pools (from 10 cats) tested positive for rickettsial infections. PCR and DNA sequencing indicated that one of the cats was positive for R. felis infections, whereas two were positive for Candidatus Rickettsia senegalensis infection. In addition, 12 of the flea pools were positive for R. felis, whereas five were positive for Ca. R. senegalensis. By contrast, no cats or their associated fleas tested positive for R. typhi. Finally, eight sera from these cats contained spotted fever group Rickettsia (SFGR) antibodies. The detection of R. felis and SFGR antibodies and the lack of R. typhi and TGR antibodies support R. felis as the main rickettsial species infecting cat fleas. The detection of Ca. R. senegalensis in both fleas and cats also provides additional evidence that cats and their associated fleas are infected with other R. felis–like organisms highlighting the potential risk for human infections with R. felis or R. felis–like organisms.

• • A Community-Designed Play-Yard Intervention to Prevent Microbial Ingestion: A Baby Water, Sanitation, and Hygiene Pilot Study in Rural Zambia

    Authors: Brie Reid, Rie Seu, Jennifer Orgle, Khrist Roy, Catherine Pongolani, Modesta Chileshe, Dadirai Fundira and Rebecca Stoltzfus

    Available online: 04 June 2018

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    Malnourished children in low-income contexts usually suffer from environmental enteric dysfunction, which is damage to the intestines caused by chronic exposure to bacterial pathogens from feces hypothesized to contribute to stunting. Many intervention studies are piloting “Baby water, sanitation, and hygiene (WASH)” to help rural farming families reduce infant and young children’s (IYC’s) exposure to human and free-range livestock feces. One proposed Baby WASH intervention is a play-yard, which consists of a baby-proofed structure (i.e., playpen) that caregivers can place IYC into while doing chores around the household yard. This article describes the pilot development and assessment of a community-built Baby WASH play-yard and a plastic play-yard intervention with 21 caregivers of 6- to 24-month-old IYC in rural Zambia. A modified Trials of Improved Practices approach was used to conduct three visits in each household: an introductory visit during which play-yard use was explained, a second visit consisting of a semi-structured interview and a session of behavioral counseling, and a final visit which included a 2-hour observation of play-yard use. The second and final visits also included 24-hour recalls, and all three visits included spot observations of play-yard use. Reports from caregivers suggest that the community-built play-yard protected IYC from ingesting soil and livestock feces. Barriers to intervention use included caregivers’ WASH beliefs and practices, community reactions, and play-yard maintenance. More work is needed to examine the role of women’s time use in their home environment, community reactions to the intervention, and the biological efficacy to reduce microbial ingestion.

• • Case Report: Mucosal Leishmaniasis Presenting with Nasal Septum Perforation after Almost Thirty Years

    Authors: Jesùs Rojas-Jaimes, Helena L. Frischtak, Jose Arenas and Andres G. Lescano

    Available online: 04 June 2018

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    Mucosal leishmaniasis (ML) is associated with progressive tissue destruction and granuloma formation, often after a considerable period of latency from an initial cutaneous infection. We report a case of recurrent epistaxis of 3 years duration and nasopharyngeal obstruction in a woman with treated cutaneous leishmaniasis nearly 30 years before and with no further exposure to Leishmania. Computed tomography revealed nasal septal perforation and histopathology demonstrated chronic inflammation. Microscopy was negative for amastigotes, but molecular testing of nasal mucosa biopsy detected Leishmania (Viannia) braziliensis. The patient underwent 28 days of treatment with IV sodium stibogluconate and her symptoms improved significantly. Sixteen months after treatment, she continues to have episodic epistaxis and detectable parasite load in her nasal lesion. Although ML is known to take years to decades to develop, there are few reported cases in the literature of such a long latency period. This report highlights the importance of considering ML in the differential diagnosis of chronic epistaxis in countries where leishmaniasis is endemic or in immigrants from these countries, even when presentation occurs decades after leaving an endemic region.

• • Arboviral Surveillance among Pediatric Patients with Acute Febrile Illness in Houston, Texas

    Authors: Leila C. Sahni, Rebecca S. B. Fischer, Rodion Gorchakov, Rebecca M. Berry, Daniel C. Payne, Kristy O. Murray and Julie A. Boom

    Available online: 04 June 2018

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    We instituted active surveillance among febrile patients presenting to the largest Houston-area pediatric emergency department to identify acute infections of dengue virus (DENV), West Nile virus (WNV), and chikungunya virus (CHIKV). In 2014, 1,063 children were enrolled, and 1,015 (95%) had blood and/or cerebrospinal fluid specimens available for DENV, WNV, and CHIKV testing. Almost half (49%) reported recent mosquito bites, and 6% (N = 60) reported either recent international travel or contact with an international traveler. None were positive for acute WNV; three had false-positive CHIKV results; and two had evidence of DENV. One DENV-positive case was an acute infection associated with international travel, whereas the other was identified as a potential secondary acute infection, also likely travel-associated. Neither of the DENV-positive cases were clinically recognized, highlighting the need for education and awareness. Health-care professionals should consider the possibility of arboviral disease among children who have traveled to or from endemic areas.

• • Prevalence of and Factors Associated with Negative Microscopic Diagnosis of Cutaneous Leishmaniasis in Rural Peru

    Authors: Ryan Lamm, Clark Alves, Grace Perrotta, Meagan Murphy, Catherine Messina, Juan F. Sanchez, Erika Perez, Luis Angel Rosales, Andres G. Lescano, Edward Smith, Hugo Valdivia, Jack Fuhrer and Sarah-Blythe Ballard

    Available online: 04 June 2018

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    Cutaneous leishmaniasis is endemic to South America where diagnosis is most commonly conducted via microscopy. Patients with suspected leishmaniasis were referred for enrollment by the Ministry of Health (MoH) in Lima, Iquitos, Puerto Maldonado, and several rural areas of Peru. A 43-question survey requesting age, gender, occupation, characterization of the lesion(s), history of leishmaniasis, and insect-deterrent behaviors was administered. Polymerase chain reaction (PCR) was conducted on lesion materials at the Naval Medical Research Unit No. 6 in Lima, and the results were compared with those obtained by the MoH using microscopy. Factors associated with negative microscopy and positive PCR results were identified using χ2 test, t-test, and multivariate logistic regression analyses. Negative microscopy with positive PCR occurred in 31% (123/403) of the 403 cases. After adjusting for confounders, binary multivariate logistic regression analyses revealed that negative microscopy with positive PCR was associated with patients who were male (adjusted OR = 1.93 [1.06–3.53], P = 0.032), had previous leishmaniasis (adjusted OR = 2.93 [1.65–5.22], P < 0.0001), had larger lesions (adjusted OR = 1.02 [1.003–1.03], P = 0.016), and/or had a longer duration between lesion appearance and PCR testing (adjusted OR = 1.12 [1.02–1.22], P = 0.017). Future research should focus on further exploration of these underlying variables, discovery of other factors that may be associated with negative microscopy diagnosis, and the development and implementation of improved testing in endemic regions.

• • Snakebite: An Exploratory Cost-Effectiveness Analysis of Adjunct Treatment Strategies

    Authors: Benjamin Herzel, Stephen P. Samuel, Tommaso C. Bulfone, C. Soundara Raj, Matthew Lewin and James G. Kahn

    Available online: 04 June 2018

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    The cost-effectiveness of the standard of care for snakebite treatment, antivenom, and supportive care has been established in various settings. In this study, based on data from South Indian private health-care providers, we address an additional question: “For what cost and effectiveness values would adding adjunct-based treatment strategies to the standard of care for venomous snakebites be cost-effective?” We modeled the cost and performance of potential interventions (e.g., pharmacologic or preventive) used adjunctively with antivenom and supportive care for the treatment of snakebite. Because these potential interventions are theoretical, we used a threshold cost-effectiveness approach to explore this forward-looking concept. We examined economic parameters at which these interventions could be cost-effective or even cost saving. A threshold analysis was used to examine the addition of new interventions to the standard of care. Incremental cost-effectiveness ratios were used to compare treatment strategies. One-way, scenario, and probabilistic sensitivity analyses were conducted to analyze parameter uncertainty and define cost and effectiveness thresholds. Our results suggest that even a 3% reduction in severe cases due to an adjunct strategy is likely to reduce the cost of overall treatment and have the greatest impact on cost-effectiveness. In this model, for example, an investment of $10 of intervention that reduces the incidence of severe cases by 3%, even without changing antivenom usage patterns, creates cost savings of $75 per individual. These findings illustrate the striking degree to which an adjunct intervention could improve patient outcomes and be cost-effective or even cost saving.

• • Anopheles Salivary Biomarker as a Proxy for Estimating Plasmodium falciparum Malaria Exposure on the Thailand–Myanmar Border

    Authors: Phubeth Ya-Umphan, Dominique Cerqueira, Gilles Cottrell, Daniel M. Parker, Freya J. I. Fowkes, Francois Nosten and Vincent Corbel

    Available online: 04 June 2018

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    Timely identification and treatment of malaria transmission “hot spots” is essential to achieve malaria elimination. Here we investigate the relevance of using an Anopheles salivary biomarker to estimate Plasmodium falciparum malaria exposure risk along the Thailand–Myanmar border to guide malaria control. Between May 2013 and December 2014, > 9,000 blood samples collected in a cluster randomized control trial were screened with serological assays to measure the Ab responses to Anopheles salivary antigen (gSG6-P1) and P. falciparum malaria antigens (CSP, merozoite surface protein 119 [MSP-119]). Plasmodium falciparum infections were monitored through passive and active case detection. Seroprevalence to gSG6-P1, MSP-119, and CSP were 71.8% (95% Confidence interval [CI]: 70.9, 72.7), 68.6% (95% CI: 67.7, 69.5), and 8.6% (95% CI: 8.0, 9.2), respectively. Multivariate analysis showed that individuals with the highest Ab response to gSG6-P1 had six times the odds of being positive to CSP antigens (P < 0.001) and two times the odds of P. falciparum infection compared with low gSG6-P1 responders (P = 0.004). Spatial scan statistics revealed the presence of clusters of gSG6-P1 that partially overlapped P. falciparum infections. The gSG6-P1 salivary biomarker represents a good proxy for estimating P. falciparum malaria risk and could serve to implement hot spot–targeted vector control interventions to achieve malaria elimination.

• • Differential Effects of Temperature and Mosquito Genetics Determine Transmissibility of Arboviruses by Aedes aegypti in Argentina

    Authors: Alexander T. Ciota, Pamela A. Chin, Dylan J. Ehrbar, Maria Victoria Micieli, Dina M. Fonseca and Laura D. Kramer

    Available online: 04 June 2018

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    Aedes aegypti (L.) (Diptera: Culicidae) have a global distribution and are the primary vector of a number of mosquito-borne viruses responsible for epidemics throughout the Americas. As in much of South America, the threat from pathogens including dengue virus (DENV; Flaviviridae, Flavivirus) and chikungunya virus (CHIKV; Togaviridae, Alphavirus) has increased in Argentina in recent years. The complexity of transmission cycles makes predicting the occurrence and intensity of arbovirus outbreaks difficult. To gain a better understanding of the risk of DENV and CHIKV in Argentina and the factors influencing this risk, we evaluated the role of population and temperature in the vector competence and vectorial capacity (VC) of Ae. aegypti from geographically and ecologically distinct locations. Our results demonstrate that intrinsic and extrinsic factors including mosquito population, viral species, and temperature significantly influence both vector competence and overall VC of Ae. aegypti in Argentina, yet also that the magnitude of these influences is highly variable. Specifically, results suggest that CHIKV competence is more dependent on mosquito genetics than is DENV competence, whereas temperature has a greater effect on DENV transmission. In addition, although there is an overall positive correlation between temperature and competence for both viruses, there are exceptions to this for individual virus–population combinations. Together, these data establish large variability in VC for these pathogens among distinct Ae. aegypti populations in Argentina and demonstrate that accurate assessment of arbovirus risk will require nuanced models that fully consider the complexity of interactions between virus, temperature, mosquito genetics, and hosts.

• • Powassan Virus and Other Arthropod-Borne Viruses in Wildlife and Ticks in Ontario, Canada

    Authors: Kathryn Smith, Paul T. Oesterle, Claire M. Jardine, Antonia Dibernardo, Chris Huynh, Robbin Lindsay, David L. Pearl, Angela M. Bosco-Lauth and Nicole M. Nemeth

    Available online: 04 June 2018

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    Powassan virus (POWV) is a tick-borne zoonosis maintained in natural enzootic cycles between ixodid ticks and wild mammals. Reported human cases have increased in recent years; these infections can be fatal or lead to long-term neurologic sequelae. However, both the geographic distribution and the role of common, potential mammalian hosts in POWV transmission are poorly understood, creating challenges to public health surveillance. We looked for evidence of POWV infection among candidate wildlife host species and ticks collected from mammals and birds in southern Ontario. Tissues (including blood) and ticks from trapped wild mammals were collected in the summers of 2015 and 2016. Ticks removed from dogs in 2015–2016 and wildlife diagnostic cases from 2011 to 2013 were also included. Tissue and tick (Ixodes spp.) homogenates were tested for POWV by reverse transcriptase–polymerase chain reaction (RT-PCR). In addition, sera from wild mammals were tested for antibodies to POWV, West Nile virus (WNV), and heartland virus (HRTV) by plaque reduction neutralization test. All 724 tissue samples were negative for POWV by RT-PCR. One of 53 pools of Ixodes cookei (among 98 total tick pools) was RT-PCR positive for deer tick virus (POWV) lineage. Antibodies to POWV and WNV were detected in 0.4% of 265 and 6.1% of 264 samples, respectively, and all of 219 serum samples tested negative for anti-HRTV antibodies. These results reveal low POWV detection rates in southern Ontario, while highlighting the challenges and need for continued efforts into understanding POWV epidemiology and targeted surveillance strategies.

• • Serological Evidence of Ebola Virus Infection in Rural Guinea before the 2014 West African Epidemic Outbreak

    Authors: Alpha K. Keita, Christelle Butel, Guillaume Thaurignac, Aminata Diallo, Talla Nioke, Falaye Traoré, Lamine Koivogui, Martine Peeters, Eric Delaporte and Ahidjo Ayouba

    Available online: 04 June 2018

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    Questions remain as whether an unnoticed Ebola outbreak has occurred in Guinea before the 2014–2016 epidemic. To address this, we used a highly sensitive and specific Luminex-based assay for Ebola virus (EBOV) antibody detection to screen blood samples collected in the framework of the Demographic Health Survey performed in 2012 in Guinea. One sample (GF069) of 1,483 tested was positive at very high immunoglobulin G titer to Zaire EBOV in Guinée Forestière. Thus, at least 2 years before the 2014 EVD outbreak in Guinea, Zaire EBOV was circulating in rural areas of this country.

• • Using Reference Quantitative Polymerase Chain Reaction to Assess the Clinical Performance of the Paracheck-Pf® Rapid Diagnostic Test in a Field Setting in Uganda

    Authors: Catherine J. Mitran, Anthony K. Mbonye, Michael Hawkes and Stephanie K. Yanow

    Available online: 04 June 2018

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    Malaria rapid diagnostic tests (RDTs) are widely used in clinical and surveillance settings. However, the performance of most RDTs has not been characterized at parasite densities below detection by microscopy. We present findings from Uganda, where RDT results from 491 participants with suspected malaria were correlated with quantitative polymerase chain reaction (qPCR)-defined parasitemia. Compared with qPCR, the sensitivity and specificity of the RDT for Plasmodium falciparum mono-infections were 76% (95% confidence interval [CI]: 68–83%) and 95% (95% CI: 92–97%), respectively. The sensitivity of the RDT at parasite densities between 0.2 and 200 parasites/μL was surprisingly high (87%, 95% CI: 74–94%). The high sensitivity of the RDT is likely because of histidine-rich protein 2 from submicroscopic infections, gametocytes, or sequestered parasites. These findings underscore the importance of evaluating different RDTs in field studies against qPCR reference testing to better define the sensitivity and specificity, particularly at low parasite densities.

• • Poor Sensitivity of Commercial Rapid Diagnostic Tests for Hepatitis B e Antigen in Senegal, West Africa

    Authors: Abdoulaye Seck, Fatou Ndiaye, Sarah Maylin, Babacar Ndiaye, François Simon, Anna L. Funk, Arnaud Fontanet, Kazuaki Takahashi, Sheikh Mohammad Fazle Akbar, Shunji Mishiro, Raymond Bercion, Muriel Vray and Yusuke Shimakawa

    Available online: 04 June 2018

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    Limited access to nucleic acid tests for hepatitis B virus (HBV) DNA is a significant barrier to the effective management of chronic HBV infection in resource-poor countries. Alternatively, HBV e antigen (HBeAg) may accurately indicate high viral replication. We assessed the diagnostic performance of three commercially available rapid diagnostic tests (RDTs) for HBeAg (SD Bioline, Insight and OneStep) against a quantitative chemiluminescent immunoassay (CLIA, Architect). Using stored sera from adults with chronic HBV infection, we tested RDTs in three groups in Senegal (48 HBeAg-positive, 196 HBeAg-negative, and 117 cases with high HBV DNA (≥ 106 IU/mL)) and one group in France (17 HBeAg-positive East Asians). In Senegal, the sensitivity and specificity for HBeAg detection were 29.8% and 100% for SD Bioline, 31.1% and 100% for Insight, and 42.5% and 98.4% for OneStep, respectively. The lower limits of detection of these RDTs were very high (> 2.5 log10 Paul Ehrlich Institut units/mL). Their low sensitivity was also confirmed in HBeAg-positive Asian samples (35.3–52.9%). The prevalence of HBeAg in highly viremic (≥ 106 IU/mL) Senegalese patients was low: 58.1% using CLIA and 24.5–37.5% using RDTs. Hepatitis B e antigen prevalence was similarly low in a subgroup of 28 Senegalese women of childbearing age with a high viral load (≥ 106 IU/mL). Approximately, half of highly viremic adults do not carry HBeAg in Africa, and HBeAg RDTs had remarkably poor analytical and diagnostic sensitivity. This implies that HBeAg-based antenatal screening, particularly if using the currently available HBeAg RDTs, may overlook most pregnant women at high risk of mother-to-child transmission in Africa.

• • Watch and Wait Approach for Inactive Echinococcal Cyst of the Liver: An Update

    Authors: Raffaella Lissandrin, Francesca Tamarozzi, Mara Mariconti, Tommaso Manciulli, Enrico Brunetti and Ambra Vola

    Available online: 04 June 2018

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    Human cystic echinococcosis (CE) is a chronic, complex and neglected infection causing severe disease in humans. Hepatic CE cysts are detected and classified mainly by using ultrasound. Expert opinion and published data suggest that uncomplicated inactive liver cysts do not require treatment and only need to be monitored over time (“Watch and Wait”). Here we update our findings as published in 2014 on the “Watch and Wait” approach applied to inactive, asymptomatic cysts of the liver to keep the medical community informed. Clinical data of patients who accessed the World Health Organization Collaborating Center for CE at the University of Pavia-San Matteo Hospital Foundation from January 1991 to October 2017 were analyzed. Inclusion criteria were presence of one or more inactive uncomplicated cysts in the liver (CE4 or CE5), without any history of previous treatment, and an ultrasound-based follow-up of at least 24 months. Fifty-three patients with 66 inactive cysts fulfilled the inclusion criteria. Of these, 11 patients are newly described here; 37 were part of our previously described cohort and the follow-up for 17 of them was further extended; and five were excluded from the previously published analysis as their follow-up was too short, but could be included now. Without the need for treatment and without development of complications, 98.5% of cysts remained inactive over time. In only one patient (1.9% of patients), a reactivation of one cyst (1.5% of cysts) was observed.

• • Dracunculiasis Eradication: Are We There Yet?

    Authors: Donald R. Hopkins, Ernesto Ruiz-Tiben, Mark L. Eberhard, Adam Weiss, P. Craig Withers Jr.,, Sharon L. Roy and Dean G. Sienko

    Available online: 04 June 2018

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    This report summarizes the status of the global Dracunculiasis Eradication Program as of the end of 2017. Dracunculiasis (guinea worm disease) has been eliminated from 19 of 21 countries where it was endemic in 1986, when an estimated 3.5 million cases occurred worldwide. Only Chad and Ethiopia reported cases in humans, 15 each, in 2017. Infections of animals, mostly domestic dogs, with Dracunculus medinensis were reported in those two countries and also in Mali. Insecurity and infections in animals are the two main obstacles remaining to interrupting dracunculiasis transmission completely.

• • Diagnostic and Treatment Monitoring Potential of A Stool-Based Quantitative Polymerase Chain Reaction Assay for Pulmonary Tuberculosis

    Authors: Andrew R. DiNardo, Alexander W. Kay, Gugu Maphalala, Nadine M. Harris, Celia Fung, Godwin Mtetwa, Pilar Ustero, Sindisiwe Dlamini, Ngan Ha, Edward A. Graviss, Rojelio Mejia and Anna M. Mandalakas

    Available online: 23 April 2018

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    A quantifiable, stool-based, Mycobacterium tuberculosis (Mtb) test has potential complementary value to respiratory specimens. Limit of detection (LOD) was determined by spiking control stool. Clinical test performance was evaluated in a cohort with pulmonary tuberculosis (TB) (N = 166) and asymptomatic household TB child contacts (N = 105). Stool-quantifiable polymerase chain reaction (qPCR) results were compared with sputum acid-fast bacilli (AFB) microscopy, GeneXpert MTB/RIF (Xpert MTB/RIF), and cultures. In Mtb stool-spiking studies, the LOD was 96 colony-forming units/50 mg of stool (95% confidence interval [CI]: 84.8–105.6). Among specimens collected within 72 hours of antituberculosis treatment (ATT) initiation, stool qPCR detected 22 of 23 (95%) of culture-positive cases. Among clinically diagnosed cases that were Xpert MTB/RIF and culture negative, stool qPCR detected an additional 8% (3/37). Among asymptomatic, recently TB-exposed participants, stool PCR detected Mtb in two of 105 (1.9%) patients. Two months after ATT, the Mtb quantitative burden in femtogram per microliters decreased (Wilcoxon signed-rank P < 0.001) and persistent positive stool PCR was associated with treatment failure or drug resistance (relative risk 2.8, CI: 1.2–6.5; P = 0.012). Stool-based qPCR is a promising complementary technique to sputum-based diagnosis. It detects and quantifies low levels of stool Mtb DNA, thereby supporting adjunct diagnosis and treatment monitoring in pulmonary TB.

• • Molecular Identification of Onchocerca spp. Larvae in Simulium damnosum sensu lato Collected in Northern Uganda

    Authors: Guilherme G. Verocai, Hassan K. Hassan, Thomson Lakwo, Peace Habomugisha, Moses N. Katabarwa, Stephen Begumisa, Philbert Clouds, James Katamanywa, Christine Nahabwe and Thomas R. Unnasch

    Available online: 02 October 2017

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    Previous studies have demonstrated that the presence of larvae of other filarial species in Simulium damnosum sensu lato can distort estimates of transmission potential for Onchocerca volvulus in West Africa. However, studies conducted in foci of onchocerciasis in West Central Uganda indicated that larvae other than O. volvulus were not common in vectors collected there. Recent data collected in Northern Uganda revealed a striking discordance between estimates of the prevalence of flies carrying O. volvulus infective larvae obtained from molecular pool screening and dissection methods. To resolve this discrepancy, sequences from three mitochondrially encoded genes were analyzed from the larvae collected by dissection. All larvae analyzed were Onchocerca ochengi v. Siisa, a parasite of cattle, or Onchocerca ramachandrini, a parasite of warthogs. These results suggest that nonhuman parasite larvae are common in vectors in Northern Uganda, underscoring the necessity for molecular identification methods to accurately estimate O. volvulus transmission.