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• • Karyotype Evolution of Chagas Disease Vectors (Hemiptera, Triatominae)

    Authors: Kaio Cesar Chaboli Alevi, Jader de Oliveira, João Aristeu da Rosa and Maria Tercília Vilela de Azeredo-Oliveira

    Available online: 21 May 2018

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    The Triatominae subfamily is composed of 153 hematophagous species that are potential vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Karyotypic studies in triatomines were initiated in 1909. There are 92 karyotypes described, all grouped into the tribes Rhodniini and Triatomini. Recently, a phylogenetic study of the triatomines that combines molecular data with geological changes was performed. We now discuss how the karyotype evolved with the diversification of the triatomines.

• • Case Report: Successful Treatment of Chromoblastomycosis Caused by Fonsecaea monophora in a Patient with Psoriasis Using Itraconazole and Acitretin

    Authors: Fangfang Bao, Qihua Wang, Changping Yu, Panpan Shang, Lele Sun, Guizhi Zhou, Mei Wu and Furen Zhang

    Available online: 21 May 2018

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    Chromoblastomycosis is a worldwide chronic subcutaneous infection caused by dematiaceous fungi and clinically characterized by verrucous lesions. Herein, we report a rare case of chromoblastomycosis caused by Fonsecaea monophora in a 60-year-old male carpenter with a 40-year history of psoriasis from Shandong in northern China. A fungal infection coexisting with psoriasis presents a management dilemma. Our patient responded well to combined itraconazole and acitretin therapy and the lesions resolved completely after 1 month of treatment.

• • Cholera Outbreak due to Raw Seafood Consumption in South Korea, 2016

    Authors: Jeong Hyun Kim, Jin Lee, Sahyun Hong, Sangwon Lee, Hae-young Na, Young-Il Jeong, Eun Jin Choi, Junyoung Kim, Hyo Sun Kawk and Enhi Cho

    Available online: 21 May 2018

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    Three cases of cholera occurred in South Korea during a period of three weeks in August 2016. All the cases were associated with the consumption of raw seafood in southern coastal area of South Korea. Epidemiologic investigations were performed to track the spread of cholera, including persons in contact with the cholera patients, seafood, and seawater from the fish tank and marine environments. A microbiological investigation demonstrated that cholera isolated from the three patients and a seawater sample at the Korea Strait showed identical serotype (O1 Ogawa), biotype (El tor), and toxin (ctx-positive). Pulsed-field gel electrophoresis analysis showed that the three clinical strains are identical (100%) and shared 97% identity with the seawater sample.

• • Preliminary Evidence for the Absence of Cystic Echinococcosis in Gabon: A Cross-Sectional Pilot Survey in Humans and Definitive Hosts

    Authors: Felix Lötsch, Ghyslain Mombo-Ngoma, Johannes Mischlinger, Mirjam Groger, Luzia Veletzky, Ayôla Akim Adegnika, Bertrand Lell, Selidji Todagbe Agnandji, Marielle Bouyou-Akotet, Markus Obermüller, Marion Wassermann, Renate Schneider, Herbert Auer and Michael Ramharter

    Available online: 21 May 2018

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    Cystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval stage of the Echinococcus granulosus sensu lato (s.l.) complex. Although the disease is known to be highly prevalent in certain parts of North and East Africa, data on CE, both in humans and definitive hosts, are extremely scarce for Central Africa. The present study assessed the epidemiology of CE in humans and dogs in rural Gabon. An ultrasound and serologic survey was conducted in volunteers from rural villages in Gabon. A two-step approach was used for serological testing with an indirect hemagglutination assay as a screening test and Western Blot as a confirmatory test. Fecal dog samples were analyzed microscopically, and PCR amplification of nad1 and cox1 genes was performed when taeniid eggs were visible. Regional hospitals and the national reference center for parasitology in Gabon were contacted for information about previous cases of CE. Randomly selected communities were invited to participate. Three hundred and forty-eight human volunteers from these communities were screened. No suspected cases of CE were detected. Definitive host screening was performed from 128 fecal samples from representative subregions, but no eggs from E. granulosus s.l. were found. No documented cases of echinococcosis were reported from the local health-care institutions and the national diagnostic reference center in Gabon. Cystic echinococcosis seems to be very rare or absent in Gabon. The reason for this lack of evidence for echinococcosis is unknown, but the absence of livestock may play a major role.

• • Comparison of Two Genotyping Methods for Distinguishing Recrudescence from Reinfection in Antimalarial Drug Efficacy/Effectiveness Trials

    Authors: Joseph R. M. Fulakeza, Rachel L. Banda, Trancizeo R. Lipenga, Dianne J. Terlouw, Standwell C. Nkhoma and Eva Maria Hodel

    Available online: 21 May 2018

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    Genotyping of allelic variants of Plasmodium falciparum merozoite surface proteins 1 and 2 (msp-1 and msp-2), and the glutamate-rich protein is the gold standard for distinguishing reinfections from recrudescences in antimalarial drug trials. We compared performance of the recently developed 24-single-nucleotide polymorphism (SNP) Barcoding Assay against msp-1 and msp-2 genotyping in a cluster-randomized effectiveness trial of artemether–lumefantrine and dihydroartemisinin–piperaquine in Malawi. Rates of recrudescence and reinfection estimated by the two methods did not differ significantly (Fisher’s exact test; P = 0.887 and P = 0.768, respectively). There was a strong agreement between the two methods in predicting treatment outcomes and resolving the genetic complexity of malaria infections in this setting. These results support the use of this SNP assay as an alternative method for correcting antimalarial efficacy/effectiveness data.

• • Genetic Variability of Plasmodium vivax in the North Coast of Peru and the Ecuadorian Amazon Basin

    Authors: Julio A. Ventocilla, Jorge Nuñez, Laura Lorena Tapia, Carmen M. Lucas, Stephen R. Manock, Andrés G. Lescano, Kimberly A. Edgel and Paul C. F. Graf

    Available online: 14 May 2018

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    In the Peruvian North Coast (PNC), the number of Plasmodium vivax malaria cases increased steadily from 2007 to 2010 despite a significant decline in the overall number of cases in Peru during the same period. To better understand the transmission dynamics of P. vivax populations in the PNC and the neighboring Ecuadorian Amazon Basin (EAB), we studied the genetic variability and population structure of P. vivax in these areas. One hundred and twenty P. vivax isolates (58 from Piura and 37 from Tumbes in the PNC collected from 2008 to 2010 and 25 from the EAB collected in Pastaza from 2001 to 2004) were assessed by five polymorphic microsatellite markers. Genetic variability was determined by expected heterozygosity (He) and population structure by Bayesian inference cluster analysis. We found very low genetic diversity in the PNC (He = 0–0.32) but high genetic diversity in the EAB (He = 0.43–0.70). Population structure analysis revealed three distinct populations in the three locations. Six of 37 (16%) isolates from Tumbes had an identical haplotype to that found in Piura, suggesting unidirectional flow from Piura to Tumbes. In addition, one haplotype from Tumbes showed similarity to a haplotype found in Pastaza, suggesting that this could be an imported case from EAB. These findings strongly suggest a minimal population flow and different levels of genetic variability between these two areas divided by the Andes Mountains. This work presents molecular markers that could be used to increase our understanding of regional malaria transmission dynamics, which has implications for the development of strategies for P. vivax control.

• • Factors Associated with the Rapid and Durable Decline in Malaria Incidence in El Salvador, 1980–2017

    Authors: Robert A. Burton, José Eduardo Romero Chévez, Mauricio Sauerbrey, Caterina Guinovart, Angela Hartley, Geoffrey Kirkwood, Matthew Boslego, Mirna Elizabeth Gavidia, Jaime Enrique Alemán Escobar, Rachel Turkel, Richard W. Steketee, Laurence Slutsker, Kammerle Schneider and Carlos C. (Kent) Campbell

    Available online: 14 May 2018

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    A decade after the Global Malaria Eradication Program, El Salvador had the highest burden of malaria in Mesoamerica, with approximately 20% due to Plasmodium falciparum. A resurgence of malaria in the 1970s led El Salvador to alter its national malaria control strategy. By 1995, El Salvador recorded its last autochthonous P. falciparum case with fewer than 20 Plasmodium vivax cases annually since 2011. By contrast, its immediate neighbors continue to have the highest incidences of malaria in the region. We reviewed and evaluated the policies and interventions implemented by the Salvadoran National Malaria Program that likely contributed to this progress toward malaria elimination. Decentralization of the malaria program, early regional stratification by risk, and data-driven stratum-specific actions resulted in the timely and targeted allocation of resources for vector control, surveillance, case detection, and treatment. Weekly reporting by health workers and volunteer collaborators—distributed throughout the country by strata and informed via the national surveillance system—enabled local malaria teams to provide rapid, adaptive, and focalized program actions. Sustained investments in surveillance and response have led to a dramatic reduction in local transmission, with most current malaria cases in El Salvador due to importation from neighboring countries. Additional support for systematic elimination efforts in neighboring countries would benefit the region and may be needed for El Salvador to achieve and maintain malaria elimination. El Salvador’s experience provides a relevant case study that can guide the application of similar strategies in other countries committed to malaria elimination.

• • Staphylococcus aureus Bacteremia Incidence and Methicillin Resistance in Rural Thailand, 2006–2014

    Authors: Devan Jaganath, Possawat Jorakate, Sirirat Makprasert, Ornuma Sangwichian, Thantapat Akarachotpong, Somsak Thamthitiwat, Supphachoke Khemla, Triveni Defries, Henry C. Baggett, Toni Whistler, Christopher J. Gregory and Julia Rhodes

    Available online: 14 May 2018

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    Staphylococcus aureus is a common cause of bloodstream infection and methicillin-resistant S. aureus (MRSA) is a growing threat worldwide. We evaluated the incidence rate of S. aureus bacteremia (SAB) and MRSA from population-based surveillance in all hospitals from two Thai provinces. Infections were classified as community-onset (CO) when blood cultures were obtained ≤ 2 days after hospital admission and as hospital-onset (HO) thereafter. The incidence rate of HO-SAB could only be calculated for 2009–2014 when hospitalization denominator data were available. Among 147,524 blood cultures, 919 SAB cases were identified. Community-onset S. aureus bacteremia incidence rate doubled from 4.4 (95% confidence interval [CI]: 3.3–5.8) in 2006 to 9.3 per 100,000 persons per year (95% CI: 7.6–11.2) in 2014. The highest CO-SAB incidence rate was among adults aged 50 years and older. Children less than 5 years old had the next highest incidence rate, with most cases occurring among neonates. During 2009–2014, there were 89 HO-SAB cases at a rate of 0.13 per 1,000 hospitalizations per year (95% CI: 0.10–0.16). Overall, MRSA prevalence among SAB cases was 10% (90/911) and constituted 7% (55/736) of CO-SAB and 20% (22/111) of HO-SAB without a clear temporal trend in incidence rate. In conclusion, CO-SAB incidence rate has increased, whereas MRSA incidence rate remained stable. The increasing CO-SAB incidence rate, especially the burden on older adults and neonates, underscores the importance of strong SAB surveillance to identify and respond to changes in bacteremia trends and antimicrobial resistance.

• • Seasonal and Temporal Trends in Childhood Conjunctivitis in Burkina Faso

    Authors: Ali Sié, Abdramane Diarra, Ourohiré Millogo, Augustin Zongo, Elodie Lebas, Till Bärnighausen, James Chodosh, Travis C. Porco, Michael S. Deiner, Thomas M. Lietman, Jeremy D. Keenan and Catherine E. Oldenburg

    Available online: 14 May 2018

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    Acute conjunctivitis follows a seasonal pattern. Although its clinical course is typically self-limited, conjunctivitis epidemics incur a substantial economic burden because of missed school and work days. This study investigated seasonal and temporal trends of childhood conjunctivitis in the entire country of Burkina Faso from 2013 to 2016, using routine monthly surveillance from 2,444 government health facilities. A total of 783,314 cases were reported over the 4-year period. Conjunctivitis followed a seasonal pattern throughout the country, with a peak in April. A nationwide conjunctivitis outbreak with a peak in September 2016 was noted (P < 0.001), with an excess number of cases first detected in June 2016. Nationwide passive surveillance was able to detect an epidemic 3 months before its peak, which may aide in allocation of resources for containment and mitigation of transmission in future outbreaks.

• • Evaluation of Standard and Mobile Health–Supported Clinical Diagnostic Tools for Assessing Dehydration in Patients with Diarrhea in Rural Bangladesh

    Authors: Saadiyah Bilal, Eric Nelson, Lars Meisner, Mahfuj Alam, Saad Al Amin, Yokabed Ashenafi, Shivani Teegala, Md Khan, Nur Alam and Adam Levine

    Available online: 14 May 2018

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    Diarrhea remains a leading cause of morbidity and mortality in patients worldwide. The objective of this study was to determine the relative inter-rater reliability and usability of standard and Mobile health (mHealth)-supported World Health Organization (WHO) algorithms for dehydration assessment in patients with acute diarrhea in a rural, low-income country hospital. Two nurses blinded to each other’s examinations assessed dehydration status on patients soon after hospital arrival using either the standard WHO algorithm printed on a laminated card or an mHealth-supported WHO algorithm downloaded onto a smartphone. The assignment of assessment tool was based on odd or even enrollment date. The inter-rater reliability for dehydration assessment between the two nurses was calculated using Cohen’s K statistic for each study group. A total of 496 patients (< 5 years N = 349, > 5 years N = 147) were enrolled in the study; 132 (27%) had some or severe dehydration, and 364 (73%) had no dehydration on arrival. Cohen’s K statistic demonstrated greater reliability for the mHealth-supported dehydration assessment (0.59) compared with the standard assessment (0.50) in the overall population (P < 0.0001), as well as in the pediatric (0.43 versus 0.37, P < 0.0001) and adult (0.79 versus 0.57, P < 0.0001) populations individually. This is the first study to show that mHealth can improve the reliability of nursing dehydration assessment in patients with acute diarrhea and the first to report on the reliability of the WHO algorithm in adult patients specifically. Future studies should focus on the impact of mHealth-supported dehydration assessment on patient-centered outcomes and examine its reliability in different settings worldwide.

• • Evaluation of Argentinean Bird Species as Amplifying Hosts for St. Louis Encephalitis Virus (Flavivirus, Flaviviridae)

    Authors: Adrián Díaz, Fernando S. Flores, Agustín I. Quaglia and Marta S. Contigiani

    Available online: 14 May 2018

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    St.Louis encephalitis virus (SLEV) is an emerging human pathogen flavivirus in Argentina. Recently, it has reemerged in the United States. We evaluated the role as amplifying host of six resident bird species and analyzed their capacity as host during the 2005 encephalitis outbreak of SLEV in Córdoba. Eared dove, picui ground dove, and house sparrow were the three species with highest host competence index. At a city level, eared doves and picui ground doves were the most important amplifying hosts during the 2005 SLEV human outbreak in Córdoba city. This finding highlighted important differences in the SLEV ecology between Argentina and the United States. Characterizing and evaluating the SLEV hosts contribute to our knowledge about its ecology and could help us to understand the causes that promote its emergence as a human pathogen in South America.

• • Malaria Elimination: Time to Target All Species

    Authors: Andrew A. Lover, J. Kevin Baird, Roly Gosling and Ric Price

    Available online: 14 May 2018

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    Important strides have been made within the past decade toward malaria elimination in many regions, and with this progress, the feasibility of eradication is once again under discussion. If the ambitious goal of eradication is to be achieved by 2040, all species of Plasmodium infecting humans will need to be targeted with evidence-based and concerted interventions. In this perspective, the potential barriers to achieving global malaria elimination are discussed with respect to the related diversities in host, parasite, and vector populations. We argue that control strategies need to be reorientated from a sequential attack on each species, dominated by Plasmodium falciparum to one that targets all species in parallel. A set of research themes is proposed to mitigate the potential setbacks on the pathway to a malaria-free world.

• • Treatment Delay among Pulmonary Tuberculosis Patients within the Pakistan National Tuberculosis Control Program

    Authors: Shahab E. Saqib, Mokbul Morshed Ahmad, Carmen Amezcua-Prieto and Martínez-Ruiz Virginia

    Available online: 14 May 2018

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    Delay in diagnosis and treatment worsens the disease and clinical outcomes, which further enhances transmission of tuberculosis (TB) in the community. Therefore, this study aims to assess treatment delay and its associated factors among pulmonary TB patients in Pakistan. A cross-sectional study was conducted among 269 pulmonary TB patients in the district. Binary and multivariate logistic regressions were used to explore the factors associated with delay in TB treatment. Results reveal that most patients were from low socioeconomic backgrounds. For example, 74.7% were living in kacha houses, 54.7% were from lowest the income group (< 250 USD/month), 60.2% married, 54.3% illiterate, 62.5% rural, 56.1% had no house ownership, and 56.5% had insufficient income for daily family expenditures. Significant delays were revealed by this study: 160 patients had experienced a delay of more than 4 weeks, whereas the median delay was 5 weeks. Results show that the most important reason for patient delay was low income and poverty (42.0%) followed by unaware of TB center (41.6), stigma (felt ashamed = 38.7%), and treatment from local traditional healers. Old age (adjusted odds ratio [AOR] = 6.6; 95% confidence interval [CI] = 1.63–26.95); and rural areas patients (AOR = 2.1; 95% CI = 1.15–3.71) were more likely to have experienced delay. However, the higher income and sufficient income category (AOR = 0.5; 95% CI = 0.31–0.95) were associated factors and less likely to experience delay in patient treatment. Integrative prevention interventions, such as those involving community leaders, health extension workers such as lady health workers, and specialized TB centers, would help to reduce delay and expand access to TB-care facilities.

• • A Deadly Wait for U.S. Health Insurance Coverage—Sitting on the Couch with Malaria

    Authors: Jonathan S. Schultz, Adam J. Atherly and Andrés F. Henao-Martínez

    Available online: 14 May 2018

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    Uninsured and unprepared travelers to countries with endemic tropical diseases pose great health-care burdens and financial risks on returning to the United States. We discuss the delayed presentation of an uninsured U.S. traveler returning from West Africa with severe malaria who required intensive care measures to save his life. Despite being critically ill on his return, he sat rigoring on his couch taking antipyretics for 3 days, while he applied for insurance on the Affordable Care Act website and waited for approval because he was fearful of the costs of seeking care. He also had limited access to affordable pretravel consultation and prophylactic medications and did not take them because he had no insurance. Average fees for a malaria hospitalization cost $25,789; however, this patient accumulated fees nearing $300,000—and his care was reimbursed by emergency Medicaid with $39,000, because his newly accepted insurance did not cover his hospitalization. This patients’ experience in the U.S. health-care system with a deadly tropical disease exemplifies the need for affordable universal coverage of pretravel consultation and malaria prophylaxis. In this uncertain political time and the recent removal of the health insurance mandate, along with the White House and Congress wanting to reform health care, this case supports the American Society of Tropical Medicine and Hygiene (ASTMH) statements showing the need for funding of tropical medicine education, research, and public health services for travelers, not cuts to important agencies and insurances that keep our country safe from imported deadly tropical diseases.

• • Zika Virus: Knowledge Assessment of Residents and Health-Care Providers in Roatán, Honduras, following an Outbreak

    Authors: Daniela I. Brissett, Cascade Tuholske, Isabel E. Allen, Noely S. Larios, Diego J. Mendoza, Ana G. Murillo and Evan M. Bloch

    Available online: 14 May 2018

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    Few studies have evaluated the effectiveness of Zika virus (ZIKV) public health educational campaigns. Following a ZIKV educational campaign in Roatán, Honduras (October 2016), a survey was administered (March–May 2017) to residents (N = 348) and health-care professionals ([HCPs]; N = 44) to evaluate ZIKV knowledge, attitudes, and preventive practices, with attention to sexual health. Knowledge scores were calculated and mapped using participants’ home locations. The knowledge scores between HCPs and residents were significantly different (mean 17 versus 11; P < 0.001). Only 6% of residents and 14% of HCPs knew that ZIKV was sexually transmissible. Few reported abstinence (2.6% residents; 9.4% HCPs) or condom use (1.6% residents; 12.5% HCPs) to prevent ZIKV infection. Of all subjects, 15.6% were pregnant or had a pregnant partner in the past year; 57.6% expressed concern over ZIKV. Mapping demonstrated spatial heterogeneity in knowledge. The findings suggest a need for improved public health messaging in ZIKV-affected areas.

• • Leptospirosis among Returned Travelers: A GeoSentinel Site Survey and Multicenter Analysis—1997–2016

    Authors: Sophia G. de Vries, Benjamin J. Visser, Rhett J. Stoney, Jiri F. P. Wagenaar, Emmanuel Bottieau, Lin H. Chen, Annelies Wilder-Smith, Mary Wilson, Christophe Rapp, Karin Leder, Eric Caumes, Eli Schwartz, Noreen A. Hynes, Abraham Goorhuis, Douglas H. Esposito, Davidson H. Hamer, Martin P. Grobusch and for the GeoSentinel Surveillance Network

    Available online: 14 May 2018

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    Leptospirosis is a potentially fatal emerging zoonosis with worldwide distribution and a broad range of clinical presentations and exposure risks. It typically affects vulnerable populations in (sub)tropical countries but is increasingly reported in travelers as well. Diagnostic methods are cumbersome and require further improvement. Here, we describe leptospirosis among travelers presenting to the GeoSentinel Global Surveillance Network. We performed a descriptive analysis of leptospirosis cases reported in GeoSentinel from January 1997 through December 2016. We included 180 travelers with leptospirosis (mostly male; 74%; mostly tourists; 81%). The most frequent region of infection was Southeast Asia (52%); the most common source countries were Thailand (N = 52), Costa Rica (N = 13), Indonesia, and Laos (N = 11 each). Fifty-nine percent were hospitalized; one fatality was reported. We also distributed a supplemental survey to GeoSentinel sites to assess clinical and diagnostic practices. Of 56 GeoSentinel sites, three-quarters responded to the survey. Leptospirosis was reported to have been most frequently considered in febrile travelers with hepatic and renal abnormalities and a history of freshwater exposure. Serology was the most commonly used diagnostic method, although convalescent samples were reported to have been collected infrequently. Within GeoSentinel, leptospirosis was diagnosed mostly among international tourists and caused serious illness. Clinical suspicion and diagnostic workup among surveyed GeoSentinel clinicians were mainly triggered by a classical presentation and exposure history, possibly resulting in underdiagnosis. Suboptimal usage of available diagnostic methods may have resulted in additional missed, or misdiagnosed, cases.

• • Arbovirus Surveillance near the Mexico–U.S. Border: Isolation and Sequence Analysis of Chikungunya Virus from Patients with Dengue-like Symptoms in Reynosa, Tamaulipas

    Authors: S. Viridiana Laredo-Tiscareño, Carlos Machain-Williams, Mario A. Rodríguez-Pérez, Javier A. Garza-Hernandez, Gloria L. Doria-Cobos, Rosa C. Cetina-Trejo, Lucio A. Bacab-Cab, Chandra S. Tangudu, Jermilia Charles, Erick J. De Luna-Santillana, Julian E. Garcia-Rejon and Bradley J. Blitvich

    Available online: 14 May 2018

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    A total of 1,090 residents of the city of Reynosa, Tamaulipas, on the Mexico–U.S. border presented at hospitals and clinics of the Secretariat of Health, Mexico, in 2015 with symptoms characteristic of dengue. Dengue virus (DENV) antigen was detected by enzyme-linked immunosorbent assay in acute sera from 134 (12.3%) patients. Sera from select patients (N = 34) were also tested for chikungunya virus (CHIKV) RNA by quantitative reverse transcription–polymerase chain reaction. Thirteen (38.2%) patients, including five DENV antigen-positive patients, were positive. Sera from three CHIKV RNA-positive patients were further assayed by virus isolation in cell culture and CHIKV was recovered on each occasion. The genome of one isolate and structural genes of the other two isolates were sequenced. In conclusion, we present evidence of CHIKV and DENV coinfections in patients who live near the Mexico–U.S. border and provide the first genome sequence of a CHIKV isolate from northern Mexico.

• • In Southern Nigeria Loa loa Blood Microfilaria Density is Very Low Even in Areas with High Prevalence of Loiasis: Results of a Survey Using the New LoaScope Technology

    Authors: Emmanuel Emukah, Lindsay J. Rakers, Barminas Kahansim, Emmanuel S. Miri, Bertram E. B. Nwoke, Emily Griswold, Yisa Saka, Ifeoma Anagbogu, Emmanuel Davies, Cephas Ityonzughul, Michael D’Ambrosio, Matthew Bakalar, Daniel A. Fletcher, Thomas Nutman, Joseph Kamgno and Frank O. Richards Jr.

    Available online: 14 May 2018

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    Ivermectin treatment can cause central nervous system adverse events (CNS-AEs) in persons with very high-density Loa loa microfilaremia (≥ 30,000 mf/mL blood). Hypoendemic onchocerciasis areas where L. loa is endemic have been excluded from ivermectin mass drug administration programs (MDA) because of the concern for CNS AEs. The rapid assessment procedure for L. loa (RAPLOA) is a questionnaire survey to assess history of eye worm. If ≥ 40% of respondents report eye worm, this correlates with ≥ 2% prevalence of very high-density loiasis microfilaremia, posing an unacceptable risk of CNS-AEs after MDA. In 2016, we conducted a L. loa study in 110 ivermectin-naïve, suspected onchocerciasis hypoendemic villages in southern Nigeria. In previous RAPLOA surveys these villages had prevalences between 10% and 67%. We examined 10,605 residents using the LoaScope, a cell phone–based imaging device for rapidly determining the microfilaria (mf) density of L. loa infections. The mean L. loa village mf prevalence was 6.3% (range 0–29%) and the mean individual mf count among positives was 326 mf/mL. The maximum individual mf count was only 11,429 mf/mL, and among 2,748 persons sampled from the 28 villages with ≥ 40% RAPLOA, the ≥ 2% threshold of very high Loa mf density could be excluded with high statistical confidence (P < 0.01). These findings indicate that ivermectin MDA can be delivered in this area with extremely low risk of L. loa–related CNS-AEs. We also concluded that in Nigeria the RAPLOA survey methodology is not predictive of ≥ 2% prevalence of very high-density L. loa microfilaremia.

• • Case Report: Filaria or Megasperm? A Cause of an Ultrasonographic “Filarial Dance Sign”

    Authors: J. Brad Wiggers, Hyun-Jung Jang and Jay S. Keystone

    Available online: 14 May 2018

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    Bancroftian filariasis can cause genital abnormalities related to chronic inflammation and obstruction of the afferent lymphatic vessels, and may demonstrate a “filarial dance sign” on scrotal ultrasound with mobile echogenic particles observed. We present a patient with a positive “filarial dance sign,” travel within Latin America and negative filarial serology.

• • Comparison of the Pharmacokinetics and Ex Vivo Antimalarial Activities of Artesunate–Amodiaquine and Artemisinin–Piperaquine in Healthy Volunteers for Preselection Malaria Therapy

    Authors: Nguyen Ngoc Quang, Marina Chavchich, Chu Xuan Anh, Geoffrey W. Birrell, Karin van Breda, Thomas Travers, Kerryn Rowcliffe and Michael D. Edstein

    Available online: 07 May 2018

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    The pharmacokinetics (PK) and ex vivo activity (pharmacodynamics [PD]) of two artemisinin combination therapies (ACTs) (artemisinin–piperaquine [ARN–PPQ] [Artequick®] and artesunate–amodiaquine [ARS–AQ] [Coarsucam™]) in healthy Vietnamese volunteers were compared following 3-day courses of the ACTs for the preselection of the drugs for falciparum malaria therapy. For PK analysis, serial plasma samples were collected from two separate groups of 22 volunteers after ACT administration. Of these volunteers, ex vivo activity was assessed in plasma samples from seven volunteers who received both ACTs. The area under the concentration–time curve (AUC0–∞) was 3.6-fold higher for dihydroartemisinin (active metabolite of ARS) than that for ARN, whereas the AUC0–∞ of desethylamodiaquine (active metabolite of AQ) was 2.0-fold lower than that of PPQ. Based on the 50% inhibitory dilution values of the volunteers’ plasma samples collected from 0.25 to 3 hours after the last dose, the ex vivo activity of ARS–AQ was 2.9- to 16.2-fold more potent than that of ARN–PPQ against the drug-sensitive D6 Plasmodium falciparum line. In addition, at 1.5, 4.0, and 24 hours after the last dose, the ex vivo activity of ARS–AQ was 20.8-, 3.5-, and 8.5-fold more potent than that of ARN–PPQ against the ARN-sensitive MRA1239 line. By contrast, at 1.5 hours, the ex vivo activity of ARS–AQ was 5.4-fold more active than that of ARN–PPQ but had similar activities at 4 and 24 hours against the ARN-resistant MRA1240 line. The PK–PD data suggest that ARS–AQ possesses superior antimalarial activity than that of ARN–PPQ and would be the preferred ACT for further in vivo efficacy testing in multidrug-resistant falciparum malaria areas.

• • Treatment Outcomes of Brazilian Inmates with Treponema pallidum and Human Immunodeficiency Virus Infection: A Prospective Cohort Study

    Authors: Graciela Mendonça dos Santos Bet, Gleyce Hellen de Almeida de Souza, Júlio Croda, Maísa Estopa Correa, Romário Oliveira de Sales, Ruthe Aline da Silva Santos, Renata Viebrantz Enne Sgarbi, Renata Terumi Shiguematsu Yassuda, Ana Rita Castro Mota Coimbra, Maurício Antônio Pompílio and Simone Simionatto

    Available online: 07 May 2018

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    A prospective cohort study was conducted to evaluate the incidence and treatment outcomes of syphilis and human immunodeficiency virus (HIV) in inmates from Central Brazil. In 2013, 3,363 inmates from 12 prisons in the state of Mato Grosso do Sul were recruited, and 1,614 remained incarcerated after 1 year. The inmates were interviewed, and blood samples were collected for serological testing for Treponema pallidum and HIV infections. Inmates infected with T. pallidum or HIV within the first year were assessed for treatment using prison medical record data, based on Venereal Disease Research Laboratory test results, HIV-1 viral load, and CD4 counts. Acquired syphilis was identified in 5.8% (N = 95) of the inmates and 74% (N = 70) of them demonstrated poor treatment outcomes after 1 year. Multivariate analysis revealed that not reporting a stable partner was a risk factor for failure of syphilis treatment. Twenty-five patients had HIV (1.5%) and among those, 13 (52%) had an HIV-1 viral load > 200 copies/mL after 1 year. The incidence of T. pallidum and HIV infections was 0.5% (N = 9). The poor treatment outcomes of syphilis and HIV within Brazilian prisons demonstrate the inadequacy of public health programs. Although the incidence of these infections within the prison population is low, new cases still occur. Our results reinforce the significance of screening programs during prison admission for early detection and treatment of sexually transmitted infections.

• • Case Report: Probable Case of Spontaneous Encephalopathy Due to Loiasis and Dramatic Reduction of Loa loa Microfilariaemia with Prolonged Repeated Courses of Albendazole

    Authors: Divine B. Arrey-Agbor, Hugues C. Nana-Djeunga, Aude E. Mogoung-Wafo, Mirabelle Mafo, Christian Danwe and Joseph Kamgno

    Available online: 07 May 2018

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    Loiasis is a vector-borne parasitic disease caused by the filarial nematode Loa loa and transmitted by the tabanid vectors from the genus Chrysops. Loa loa infection is associated with clinical manifestations such as pruritus, migratory transient edema, passage of adult worm in the bulbar conjunctiva, retinal damage, glomerular damage, albuminuria, pleural effusion, hydrocele, and endomyocardial fibrosis. Data reporting the occurrence of spontaneous encephalopathy associated with loiasis are very scanty. Severe adverse events occurring post-ivermectin administered in the framework of the fight against onchocerciasis and/or lymphatic filariasis in loiasis co-endemic areas have been closely associated with very high L. loa microfilariaemia. Different regimens have been used to lower L. loa microfilariaemia before definitive treatment, and many discrepancies have been reported. We report the case of a patient who was admitted to a health facility and hospitalized for 34 days for altered consciousness, blurred vision, headache, and chills. After other potential diagnoses were eliminated, the patient was confirmed with encephalopathy due to loiasis and referred to the Centre for Research on Filariasis and other Tropical Diseases (CRFilMT). On admission at CRFilMT, the patient was harboring 28,700 microfilariae per milliliter of blood (mf/mL), and after four 21-day courses of 400 mg daily albendazole, the L. loa microfilariaemia lowered to 5,060 mf/mL. The patient was then treated with ivermectin 3 mg and a total clearance of microfilariae was observed, with satisfactory clinical evolution and no adverse event. This case study further confirmed that albendazole is effective against L. loa, but might necessitate a longer course.

• • Human and Equine Infection with Alphaviruses and Flaviviruses in Panamá during 2010: A Cross-Sectional Study of Household Contacts during an Encephalitis Outbreak

    Authors: Jean-Paul Carrera, Karoun H. Bagamian, Amelia P. Travassos da Rosa, Eryu Wang, Davis Beltran, Nathan D. Gundaker, Blas Armien, Gianfranco Arroyo, Néstor Sosa, Juan Miguel Pascale, Anayansi Valderrama, Robert B. Tesh, Amy Y. Vittor and Scott C. Weaver

    Available online: 07 May 2018

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    Members of the genera Alphavirus (family Togaviridae) and Flavivirus (family Flaviridae) are important zoonotic human and equine etiologic agents of neurologic diseases in the New World. In 2010, an outbreak of Madariaga virus (MADV; formerly eastern equine encephalitis virus) and Venezuelan equine encephalitis virus (VEEV) infections was reported in eastern Panamá. We further characterized the epidemiology of the outbreak by studying household contacts of confirmed human cases and equine cases with neurological disease signs. Sera samples were screened using a hemagglutination inhibition test, and human results were confirmed using plaque reduction neutralization tests. A generalized linear model was used to evaluate the human MADV and VEEV seroprevalence ratio by age (in tercile) and gender. Overall, antibody prevalence for human MADV infection was 19.4%, VEEV 33.3%, and Mayaro virus 1.4%. In comparison with individuals aged 2–20 years, people from older age groups (21–41 and > 41 years) were five times more likely to have antibodies against VEEV, whereas the MADV prevalence ratio was independent of age. The overall seroprevalence of MADV in equids was 26.3%, VEEV 29.4%, West nile virus (WNV) 2.6%, and St. Louis encephalitis virus (SLEV) was 38.7%. Taken together, our results suggest that multiple arboviruses are circulating in human and equine populations in Panamá. Our findings of a lack of increase in the seroprevalence ratio with age support the hypothesis of recent MADV exposure to people living in the affected region.

• • Zika Virus Prevention: U.S. Travelers’ Knowledge, Risk Perceptions, and Behavioral Intentions—A National Survey

    Authors: Linda Squiers, James Herrington, Bridget Kelly, Carla Bann, Sylvia Becker-Dreps, Lola Stamm, Mihaela Johnson and Lauren McCormack

    Available online: 07 May 2018

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    Limited data exist about U.S. travelers’ knowledge, risk perceptions, and behaviors related to the Zika virus (ZIKV). Using an internet research panel, in March 2017, we surveyed 1,202 Americans in the continental United States and Puerto Rico who planned to travel to a Zika-affected country, state, or U.S. territory in 2017. We compared levels of knowledge and perceived risk of ZIKV, and intentions to practice ZIKV prevention behaviors across respondents from three regions: Puerto Rico, at-risk states, and other states. More than 80% of respondents correctly understood that a person could acquire ZIKV through a bite from an infected mosquito, and over 64% of respondents knew that a pregnant woman could pass the virus to her fetus. Less than half of the respondents from at-risk states and other states knew that ZIKV could be transmitted sexually, as compared with three-quarters of respondents from Puerto Rico. Compared with respondents from at-risk and other states, respondents from Puerto Rico were the most knowledgeable for almost all types of knowledge assessed. Knowledge about post-travel precautions was low across all three regions. Differences in perceived risk and intentions to practice specific prevention behaviors also varied among regions. Significant gaps exist in U.S. travelers’ knowledge about how to prevent ZIKV transmission both during and after travel. Input and collaboration from the travel industry, health care providers, and the media are needed to help educate travelers about how to prevent ZIKV infection and transmission.

• • The Hidden Burden of Plasmodium vivax Malaria in Pregnancy in the Amazon: An Observational Study in northwestern Brazil

    Authors: Anaclara Pincelli, Paulo A. R. Neves, Barbara H. Lourenço, Rodrigo M. Corder, Maíra B. Malta, Juliana Sampaio-Silva, Rodrigo M. de Souza, Marly A. Cardoso, Marcia C. Castro, Marcelo U. Ferreira and for the MINA Brazil Working Group

    Available online: 07 May 2018

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    We measured the prevalence of malaria in pregnancy and estimated its impact on birth weight and length and maternal hemoglobin in 1,180 women from Juruá Valley, the main malaria hotspot in Brazil. Antenatal malaria episodes, 74.6% of them due to Plasmodium vivax, were microscopically diagnosed in 8.0% of the women and were associated with an average reduction in birth weight z-scores of 0.35 (95% confidence interval [CI] = 0.14–0.57) and in birth length z-scores of 0.31 (95% CI = 0.08–0.54), compared with malaria-free pregnancies. Affected mothers had a mean decrease in hemoglobin concentration at delivery of 0.33 g/100 mL (95% CI = 0.05–0.62 g/100 mL); 51.6% were anemic. The timing and frequency of antenatal infections influenced pregnancy outcomes and first- or second-trimester infections were not associated with decreased birth weight and length and maternal hemoglobin at delivery. Although repeated antenatal vivax infections were associated with poorer birth outcomes, even a single vivax malaria episode was associated with a significant reduction in birth weight and length and maternal hemoglobin. Overall, 7.5% women had the parasite’s DNA found in peripheral blood at delivery. Most (83.1%) of these 89 perinatal infections were due to P. vivax and only 7.9% of them progressed to symptomatic disease after delivery. Plasmodium vivax and Plasmodium falciparum DNA was found in 0.6% and 0.3% of 637 cord blood samples examined, respectively, but only one newborn developed clinical neonatal malaria. Our results further challenge the notion that vivax malaria is relatively benign during pregnancy and call for better strategies for its prevention.

• • Exhaled Nitric Oxide is Not a Biomarker for Pulmonary Tuberculosis

    Authors: José W. López, Maria-Cristina I. Loader, Dan Smith, Dan Pastorius, Marjory Bravard, Luz Caviedes, Karina M. Romero, Taryn Clark, William Checkley, Eduardo Ticona, Jon S. Friedland and Robert H. Gilman

    Available online: 30 April 2018

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    To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant–TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8–26] versus 15 ppb [IQR = 12–24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10–19] at day 60). Taking this and previous evidence together, we conclude FeNO is not of value in either the diagnosis of pulmonary TB or as a marker of treatment response.

• • Case Report: Atypical Cutaneous Manifestations of Tularemia after Horsefly Bite

    Authors: F. Drago, Sanja Javor and Aurora Parodi

    Available online: 30 April 2018

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    Tularemia is an infectious zoonosis caused by Francisella tularensis, an aerobic, noncapsulated, Gram-negative coccobacillus. It is more common in the northern hemisphere, and there are sporadic reports in nonendemic areas. The bacterium is usually transmitted by the bite or feces of a tick or other arthropods such as mosquitoes and horseflies. We report a case of an Italian patient with tularemia after a horsefly bite.

• • Congenital Chagas Disease in the United States: Cost Savings through Maternal Screening

    Authors: Eileen Stillwaggon, Victoria Perez-Zetune, Stephanie R. Bialek and Susan P. Montgomery

    Available online: 30 April 2018

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    Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors through transfusions, transplants, insect feces in food, and from mother to child during gestation. Congenital infection could perpetuate Chagas disease indefinitely, even in countries without vector transmission. An estimated 30% of infected persons will develop lifelong, potentially fatal, cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment of Chagas disease in the United States. We constructed a decision-analytic model to find the lower cost option, comparing costs of testing and treatment, as needed, for mothers and infants with the lifetime societal costs without testing and the consequent morbidity and mortality due to lack of treatment or late treatment. We found that maternal screening, infant testing, and treatment of Chagas disease in the United States are cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence above 0.06% compared with no screening program. Newly approved diagnostics make universal screening cost saving with maternal prevalence as low as 0.008%. The present value of lifetime societal savings due to screening and treatment is about $634 million saved for every birth year cohort. The benefits of universal screening for T. cruzi as part of routine prenatal testing far outweigh the program costs for all U.S. births.

• • Factors Associated with Wuchereria bancrofti Microfilaremia in an Endemic Area of Mali

    Authors: Housseini Dolo, Yaya Ibrahim Coulibaly, Louise Kelly-Hope, Siaka Konate, Benoit Dembele, Siaka Yamoussa Coulibaly, Dramane Sanogo, Lamine Soumaoro, Michel Emmanuel Coulibaly, Salif Seriba Doumbia, Abdallah Amadou Diallo, Sekou Fantamady Traore, Robert Colebunders, Thomas B. Nutman and Amy D. Klion

    Available online: 30 April 2018

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    Although Wuchereria bancrofti (Wb), the causative agent of lymphatic filariasis, is endemic throughout Mali, the prevalence of Wb microfilaremia (Mf) can vary widely between villages despite similar prevalence of infection as assessed by circulating antigen. To examine this variation, cross-sectional data obtained during screening prior to an interventional study in two neighboring villages in Mali were analyzed. The overall prevalence of Wb, as assessed by Wb Cag (circulating antigen), was 50.3% among 373 participants, aged 14-65. Wb Mf-positive and negative individuals appeared randomly distributed across the two villages (Moran’s I spatial statistic = -0.01, Z score = 0.1, P > 0.05). Among the 187 subjects positive for Wb CAg, 117 (62.5%) had detectable Mansonella perstans microfilaremia (Mp Mf) and 64(34.2%) had detectable Wb microfilaremia. The prevalence of Mp microfilaremia was 73.4% in the Wb Mf-positive group (as compared to 56.9% in the Wb Mf-negative group; p=0.01), and median Wb Mf load was increased in co-infected subjects (267 Mf/ml vs 100 Mf/ml; p < 0.001). In multivariate analysis, village of residence, Mp Mf positivity and gender were significantly associated with Wb Mf positivity. After controlling for age, gender and village of residence, the odds of being Wb Mf positive was 2.67 times higher in Mp positive individuals (95% CI [1.42-5.01]). Given the geographical overlap between Mp and Wb in Africa, a better understanding of the distribution and prevalence of Mp could assist national LF control programs in predicting areas of high Wb mf prevalence that may require closer surveillance.

• • Mosquito Infectivity and Parasitemia after Controlled Human Malaria Infection

    Authors: Jona Walk, Geert-Jan van Gemert, Wouter Graumans, Robert Sauerwein and Else M. Bijker

    Available online: 30 April 2018

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    Controlled Human Malaria Infection (CHMI) has become an increasingly important tool for the evaluation of drugs and vaccines. Controlled Human Malaria Infection has been demonstrated to be a reproducible model; however, there is some variability in time to onset of parasitemia between volunteers and studies. At our center, mosquitoes infected with Plasmodium falciparum by membrane feeding have variable and high salivary gland sporozoite load (mean 78,415; range 26,500–160,500). To determine whether this load influences parasitemia after CHMI, we analyzed data from 13 studies. We found no correlation between the sporozoite load of a mosquito batch and time to parasitemia or parasite density of first-wave parasitemia. These findings support the use of infected mosquito bite as a reproducible means of inducing P. falciparum infection and suggest that within this range, salivary gland sporozoite load does not influence the stringency of a CHMI.

• • Burden and Risk Factors of Antimicrobial Use in Under-Five Children with Diarrheal Illness in Rural Bangladesh

    Authors: Shahnawaz Ahmed, Poonum Korpe, Tahmeed Ahmed, Mohammod Jobayer Chisti and Abu Syed Golam Faruque

    Available online: 30 April 2018

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    Antimicrobial overuse contributes to antimicrobial resistance. Empiric use of antimicrobials for diarrheal illness is warranted only in a minority of cases, because of its self-limiting nature and multifactorial etiology. This study aims to describe the factors contributing to antimicrobial overuse for diarrheal disease among children less than 5 years of age in rural Bangladesh. A total of 3,570 under-five children presenting with diarrhea in a tertiary level hospital were enrolled in the study. The rate of antimicrobial use at home was 1,395 (39%), compared with 2,084 (89%) during a hospital visit. In a multivariate analysis, factors associated with antimicrobial use at home included residence located more than 5 miles from a hospital; use of zinc and oral rehydration salts at home; vomiting; greater than 10 stools per 24 hours; diarrheal duration greater than 3 days; and rotavirus diarrhea (P < 0.05 for all). Characteristics of children more likely to be given antimicrobials in a health-care setting included greater than 10 stools per 24 hours; duration of diarrhea greater than 3 days; use of antimicrobials before hospital presentation; fever (≥ 37.8°C); rectal straining; and Shigella infection (P < 0.05 for all). The most commonly used drugs in rotavirus diarrhea were azithromycin and erythromycin, both before hospital presentation and during hospital admission. Our study underscores the importance of diligent vigilance on the rationale use of antimicrobials both at home and in health-care facilities with a special concern for under-five children living in rural Bangladesh.

• • Case Report: Hemianopia: From Suspected Glioblastoma to the Diagnosis of Ectopic Schistosomiasis Haematobium Infection in a Traveler Returning from the Republic of the Congo

    Authors: Séverine Loridant, Gabriel Mouahid, Marjorie Cornu, Jean-François Allienne, Jordan Leroy, Claude Alain Maurage, Emilie Fréalle, Richard Assaker, Fahed Zairi, Emmanuel Dutoit, Hélène Moné and Boualem Sendid

    Available online: 30 April 2018

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    Schistosomiasis due to Schistosoma haematobium is a widespread disease usually affecting the urinary tract associated with hematuria and kidney disorders. Neurological damage is rarely reported and symptoms are nonspecific and may suggest brain tumors such as glioma. We describe the first double ectopic haematobium schistosomiasis case involving the brain and intestine.

• • Increased Human Incidence of West Nile Virus Disease near Rice Fields in California but Not in Southern United States

    Authors: Tony J. Kovach and A. Marm Kilpatrick

    Available online: 30 April 2018

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    Anthropogenic land use change, including agriculture, can alter mosquito larval habitat quality, increase mosquito abundance, and increase incidence of vector-borne disease. Rice is a staple food crop for more than half of the world’s population, with ∼1% of global production occurring within the United States (US). Flooded rice fields provide enormous areas of larval habitat for mosquito species and may be hotspots for mosquito-borne pathogens, including West Nile virus (WNV). West Nile virus was introduced into the Americas in 1999 and causes yearly epidemics in the US with an average of approximately 1,400 neuroinvasive cases and 130 deaths per year. We examined correlations between rice cultivation and WNV disease incidence in rice-growing regions within the US. Incidence of WNV disease increased with the fraction of each county under rice cultivation in California but not in the southern US. We show that this is likely due to regional variation in the mosquitoes transmitting WNV. Culex tarsalis was an important vector of WNV in California, and its abundance increased with rice cultivation, whereas in rice-growing areas of the southern US, the dominant WNV vector was Culex quinquefasciatus, which rarely breeds in rice fields. These results illustrate how cultivation of particular crops can increase disease risk and how spatial variation in vector ecology can alter the relationship between land cover and disease.

• • Ventricular Neurocysticercosis: A Severe Form of the Disease Waiting for Well-Designed Therapeutic Trials

    Author: Oscar H. Del Brutto

    Available online: 30 April 2018

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• • Outbreak of Chikungunya in the French Caribbean Islands of Martinique and Guadeloupe: Findings from a Hospital-Based Surveillance System (2013–2015)

    Authors: Frédérique Dorléans, Bruno Hoen, Fatiha Najioullah, Cécile Herrmann-Storck, Kinda Maria Schepers, Sylvie Abel, Isabelle Lamaury, Laurence Fagour, Raymond Césaire, Stéphanie Guyomard, Ruth Troudard, Yvette Adélaïde, Marie-José Romagne, Magguy Davidas, Séverine Rochais, Sylvie Boa, Frédérique de Saint-Alary, Annabel Preira, Patrick Saint-Martin, Amandine Vaidie, Mathilde Melin, Elise Daudens-Vaysse, Jacques Rosine, Alain Blateau, Luisiane Carvalho, Alexandra Septfons, Marie-Claire Paty, Ghislain Leduc, Sylvie Cassadou, Martine Ledrans and André Cabié

    Available online: 23 April 2018

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    Chikungunya virus (CHIKV) emerged in the Caribbean island of Saint-Martin in December 2013. We implemented a hospital-based surveillance system to detect and describe CHIKV cases including severe forms of the infection and deaths in the islands of Martinique and Guadeloupe. A case was defined as a patient with a CHIKV laboratory confirmation cared for in a public hospital for chikungunya for at least 24 hours, and a severe CHIKV case was defined as a CHIKV case presenting one or more organ failures. Sociodemographic, clinical, and laboratory data were collected and cases classified into severe or nonsevere based on medical records. From December 2013 to January 2015, a total of 1,836 hospitalized cases were identified. Rate of hospital admissions for CHIKV infection was 60 per 10,000 suspected clinical CHIKV cases and severity accounted for 12 per 10,000. A total of 74 deaths related to CHIKV infection occurred. Infants and elderly people were more frequently hospitalized compared with others and severity was more frequently reported in elderly subjects and subjects with underlying health condition. Fifteen neonatal infections consecutive to mother-to-child transmission were diagnosed, seven of which were severe. The most vulnerable groups of the population, such as the elderly, infants, individuals with comorbidities, and pregnant women, should remain the main targets of public health priorities.

• • Estimating the Risk of Vertical Transmission of Dengue: A Prospective Study

    Authors: Célia Basurko, Séverine Matheus, Hélène Hildéral, Sibille Everhard, Marion Restrepo, Emma Cuadro-Alvarez, Véronique Lambert, Rachida Boukhari, Jean-Pierre Duvernois, Anne Favre, Mathieu Nacher and Gabriel Carles

    Available online: 23 April 2018

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    The incidence of dengue worldwide is increasing rapidly. A better understanding of dengue transmission may help improve interventions against this major public health problem. The virus is mostly transmitted by vectors. There are, however, other modes of transmission, notably mother-to-child transmission or vertical transmission. We studied a prospective cohort of 54 women who had dengue while pregnant during the 2012–2013 epidemic in French Guiana to estimate the mother-to-child transmission rate and assess the clinical and biological presentation of neonatal dengue. The rate of vertical transmission was between 18.5% (95% confidence interval [CI]: 9.25–31.4) and 22.7% (95% CI: 11.5–37.8), depending on the calculation method used. Mother-to-child transmission occurred both in early and late pregnancy. There were 52 births, including three newborns who presented neonatal dengue with warning signs requiring platelet transfusion. This quantification of the mother-to-child transmission of dengue highlights three points: first, vertical transmission of dengue is not negligible; second, it is more frequent when maternal dengue occurs late during pregnancy near delivery; and third, reliable diagnostic tests must be used to allow the diagnosis of vertical transmission. Our findings indicate that if there is a known history of maternal dengue during pregnancy, or if there is fever during the 15 days before term, cord blood and placenta should be sampled after delivery and tested for the virus, and the newborn should be closely monitored during the postpartum period.

• • Socioeconomic and Behavioral Factors Associated with Tuberculosis Diagnostic Delay in Lima, Peru

    Authors: Lily V. Bonadonna, Matthew J. Saunders, Heinner Guio, Roberto O. Zegarra and Carlton A. Evans

    Available online: 23 April 2018

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    Early detection and diagnosis of tuberculosis (TB) is a global priority. Prolonged symptom duration before TB diagnosis is associated with increased morbidity, mortality, and risk of transmission. We aimed to determine socioeconomic and behavioral factors associated with diagnostic delays among patients with TB. Data were collected from 105 patients with TB using a semi-structured interview guide in Lima, Peru. Factors associated with diagnostic delay were analyzed using negative binomial regression. The median delay from when symptoms commenced and the first positive diagnostic sample in public health facilities was 57 days (interquartile range: 28–126). In multivariable analysis, greater diagnostic delay was independently associated with patient older age, female gender, lower personal income before diagnosis, living with fewer people, and having more visits to professional health facilities before diagnosis (all P < 0.05). Patients who first sought care at a private health facility had more visits overall to professional health facilities before diagnosis than those who first sought care from public or insured employee health facilities and had longer diagnostic delay in analysis adjusted for age and gender. Patients with TB were significantly more likely to first self-medicate than to visit professional health facilities before diagnosis (P = 0.003). Thus, diagnostic delay was prolonged, greatest among older, low-income women, and varied according to the type of care sought by individuals when their symptoms commenced. These findings suggest that TB case-finding initiatives should target vulnerable groups in informal and private health facilities, where many patients with TB first seek health care.

• • Outbreak of Louse-Borne Relapsing Fever among Urban Dwellers in Arsi Zone, Central Ethiopia, from July to November 2016

    Authors: Tamara Nordmann, Torsten Feldt, Matthias Bosselmann, Tafese Beyene Tufa, Gorfnesh Lemma, Martha Holtfreter and Dieter Häussinger

    Available online: 23 April 2018

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    We report epidemiological and clinical aspects of an outbreak of louse-borne relapsing fever (LBRF) in Asella in Arsi Zone, central Ethiopia, from July to November 2016. A total of 63 LBRF cases were reported. The overall case fatality rate was 13% among treated patients. In this article, the first-line epidemiological assessment, individual prevention and control measures, and public health investigations and interventions in relation to this outbreak are described. Treatment recommendations for resource-limited settings are discussed by review of the latest literature.

• • Coinfection with Enteric Pathogens in East African Children with Acute Gastroenteritis—Associations and Interpretations

    Authors: Maria Andersson, Jean-Claude Kabayiza, Kristina Elfving, Staffan Nilsson, Mwinyi I. Msellem, Andreas Mårtensson, Anders Björkman, Tomas Bergström and Magnus Lindh

    Available online: 23 April 2018

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    Enteric coinfections among children in low-income countries are very common, but it is not well known if specific pathogen combinations are associated or have clinical importance. In this analysis, feces samples from children in Rwanda and Zanzibar less than 5 years of age, with (N = 994) or without (N = 324) acute diarrhea, were analyzed by real-time polymerase chain reaction targeting a wide range of pathogens. Associations were investigated by comparing co-detection and mono-detection frequencies for all pairwise pathogen combinations. More than one pathogen was detected in 840 samples (65%). A negative association (coinfections being less common than expected from probability) was observed for rotavirus in combination with Shigella, Campylobacter, or norovirus genogroup II, but only in patients, which is statistically expected for agents that independently cause diarrhea. A positive correlation was observed, in both patients and controls, between Ct (threshold cycle) values for certain virulence factor genes in enteropathogenic Escherichia coli (EPEC) (eae and bfpA) and toxin genes in enterotoxigenic E. coli (eltB and estA), allowing estimation of how often these genes were present in the same bacteria. A significant positive association in patients only was observed for Shigella and EPEC-eae, suggesting that this coinfection might interact in a manner that enhances symptoms. Although interaction between pathogens that affect symptoms is rare, this work emphasizes the importance and difference in interpretation of coinfections depending on whether they are positively or negatively associated.

• • Physician Knowledge, Attitudes, and Practices Related to Chagas Disease in Tabasco, Mexico

    Authors: Brandon A. Berger, Allison H. Bartlett, Ricardo Jimenez Hernandez, Esmelin Trinidad Vazquez and Norma Galindo-Sevilla

    Available online: 23 April 2018

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    We designed and implemented a survey of physician knowledge, attitudes, and practices with respect to Chagas disease in the state of Tabasco, Mexico. Seventy-eight public sector physicians from across the state responded via REDCap, an online survey capture tool. Improved performance on knowledge-based questions (P < 0.01) and an increase in decisions to screen (P = 0.04) were associated with previous training specific to this disease. Our results provide important descriptive information regarding knowledge, attitudes, and practices among a group of public sector Mexican doctors and highlight the importance of Chagas disease–specific physician training for identification and, ultimately, treatment of patients affected by this disease.

• • Cryptosporidiosis Outbreak in Immunocompetent Children from a Remote Area of French Guiana

    Authors: Emilie Mosnier, Noémie Martin, Romy Razakandrainibe, Frédéric Dalle, Guillaume Roux, Arnaud Buteux, Loïc Favennec, Paul Brousse, Basma Guarmit, Denis Blanchet, Loïc Epelboin, Camille Girouin, Elise Martin, Félix Djossou, Mathieu Nacher and Magalie Demar

    Available online: 23 April 2018

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    In September 2014, an increase in the number of Cryptosporidium spp. gastrointestinal tract infections was reported over a 6-month period among children living in a remote area along the Maroni River in French Guiana. Children presented gastroenteritis symptoms with Cryptosporidium-positive stools. Questionnaires were administered and stool examinations were controlled 3 months after the onset of symptoms. Data collection included demographics, food consumption, river behavior, symptoms, and outcome. Stool specimens were tested using microscopy and polymerase chain reaction. Samples from the water systems were examined for turbidity and culture for bacteria. Data from the reference laboratory were analyzed to calculate the median cryptosporidiosis incidence among immunocompetent patients from 2008 to 2015. Data on gastroenteritis cases reported by the Delocalized Center for Prevention and Care in the area were also collected. We report a cluster of 14 cases. All cases were children, aged between 4.5 and 38 months. Seven reported moderate to severe dehydration and required hospitalization. Speciation and microbiological typing revealed the cluster strain was Cryptosporidium hominis subtype IbA10G2 but C. hominis IbA9G2 and IbA15G1 strains were also identified. The median incidence in French Guiana was 5.8 cases per year before the outbreak. The first cases of the cluster appeared in the dry season. We describe the clinical features, epidemiology, and state of current investigations for the largest documented outbreak of cryptosporidiosis in French Guiana.

• • The Prevalence of Hepatitis C Virus Antibody in HIV-Negative Persons in Kenya, 2007

    Authors: Kathleen N. Ly, Andrea A. Kim, Jan Drobenuic, Maja Kodani, Joel M. Montgomery, Barry S. Fields and Eyasu H. Teshale

    Available online: 23 April 2018

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    The prevalence of hepatitis C virus (HCV) infection in the Kenyan population has not been previously determined. We estimated the Kenyan HCV prevalence in HIV-negative persons aged 15–64 years. This is a retrospective cross-sectional study using data from the 2007 Kenya AIDS Indicator Survey—a nationally representative sample of 15,853 persons aged 15–64 years who completed a health interview and provided a blood specimen. Of the 1,091 randomly selected participants, 50 tested positive for HCV antibody using the automated chemiluminescence immunoassay, corresponding to a weighted HCV antibody positivity rate of 4.4% (95% confidence interval: 3.3–5.9%) or 848,000 (range: 634,000–1,100,000) persons. Hepatitis C virus RNA, a marker for current infection, was not detected in any of the tested antibody-positive specimens. The high HCV antibody prevalence together with no current infection suggests that some HCV antibody serologic testing in Kenya may result in false positives whereas others may be because of spontaneous viral clearance.

• • United States Travelers’ Concern about Zika Infection and Willingness to Receive a Hypothetical Zika Vaccine

    Authors: Nadja A. Vielot, Lola Stamm, James Herrington, Linda Squiers, Bridget Kelly, Lauren McCormack and Sylvia Becker-Dreps

    Available online: 23 April 2018

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    The ongoing Zika pandemic has affected many countries that are common travel destinations. We assessed the willingness to receive a prophylactic Zika virus (ZIKV) vaccine, currently under development, among travelers to areas with reported autochthonous ZIKV transmission. We surveyed United States (U.S.) residents aged 18–44 years who had ever heard of ZIKV and planned to travel to Florida and/or Texas (N = 420) or a U.S. territory or foreign country (N = 415) in 2017, using a nationally representative internet panel. Travelers to Florida and/or Texas reported less concern about ZIKV infection than travelers to other destinations (27% versus 36%, P = 0.01). Female gender, Hispanic ethnicity, discussing ZIKV with medical professionals, ZIKV risk perception, and self-efficacy for ZIKV prevention predicted concern about ZIKV infection in both groups. Travelers to Florida and/or Texas (43%) and other destinations (44%) were equally willing to receive a ZIKV vaccine. Hispanic ethnicity, discussing ZIKV with medical professionals, and concern about ZIKV infection predicted vaccine willingness in both groups. Likelihood of using existing ZIKV prevention methods, confidence in the U.S. government to prevent ZIKV spread, self-efficacy for ZIKV prevention, and knowledge about ZIKV symptoms further predicted vaccine willingness in travelers to other destinations. In multivariable analyses, the only concern about ZIKV infection was associated with vaccine willingness in both groups (prevalence ratio [95% confidence interval]: Florida and/or Texas: 1.34 [1.06, 1.69]; other: 1.82 [1.44, 2.29]). Targeted communications can educate travelers, particularly travelers who are pregnant or may become pregnant, about ZIKV risk to generate ZIKV vaccine demand, regardless of intended destinations.

• • Sulfamethoxazole Levels in HIV-Exposed Uninfected Ugandan Children

    Authors: Jingo Kasule, Erin E. Gabriel, Aggrey Anok, Jillian Neal, Richard T. Eastman, Scott Penzak, Kevin Newell, David Serwadda, Patrick E. Duffy, Steven J. Reynolds and Charlotte V. Hobbs

    Available online: 23 April 2018

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    Trimethoprim–sulfamethoxazole (TMP–SMX) prophylaxis in HIV-uninfected, exposed (HUE) children variably reduces clinical malaria burden despite antifolate resistance, but data regarding achieved serum levels and adherence are lacking. Serum samples from 70 HUE children aged 3–12 months from Rakai, Uganda, enrolled in an observational study were assayed for random SMX levels using a colorimetric assay. Adherence with TMP–SMX prophylaxis data (yes/no) was also collected. Of 148 visits with concurrent SMX levels available, 56% had self-reported adherence with TMP–SMX therapy. Among these 82 visits, mean (standard deviation) level was 19.78 (19.22) µg/mL, but 33% had SMX levels below IC50s for Plasmodium falciparum with some, but not all, of the reported antifolate resistance mutations reported in Uganda. With TMP–SMX prophylaxis, suboptimal adherence is concerning. Sulfamethoxazole levels below IC50s required to overcome malaria parasites with multiple antifolate resistance mutations may be significant. Further study of TMP–SMX in this context is needed.

• • Functional Studies of T Regulatory Lymphocytes in Human Schistosomiasis in Western Kenya

    Authors: Bartholomew N. Ondigo, Eric M. Ndombi, Sarah C. Nicholson, John K. Oguso, Jennifer M. Carter, Nupur Kittur, William Evan Secor, Diana M. S. Karanja and Daniel G. Colley

    Available online: 23 April 2018

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    Immunoregulation is considered a common feature of Schistosoma mansoni infections, and elevated levels of T regulatory (Treg) lymphocytes have been reported during chronic human schistosomiasis. We now report that the removal of Treg (CD4+/CD25hi/CD127low lymphocytes) from peripheral blood mononuclear cells (PBMCs) of S. mansoni–infected individuals leads to increased levels of phytohemagglutinin (PHA)-stimulated interferon gamma (IFNγ) production and decreased interleukin-10 (IL-10) responses. Exposure to schistosome antigens did not result in measurable IFNγ by either PBMC or Treg-depleted populations. Interleukin-10 responses to soluble egg antigens (SEA) by PBMC were unchanged by Treg depletion, but the depletion of Treg greatly the decreased IL-10 production to soluble worm antigenic preparation (SWAP). Proliferative responses to PHA increased upon Treg removal, but responses to SEA or SWAP did not, unless only initially low responders were evaluated. Addition of anti-IL-10 increased PBMC proliferative responses to either SEA or SWAP, but did not alter responses by Treg-depleted cells. Blockade by anti-TGF-β increased SEA but not SWAP proliferative responses by PBMC, whereas anti-TGF-β increased both SEA- and SWAP-stimulated responses by Treg-depleted cultures. Addition of both anti-IL-10 and anti-TGF-β to PBMC or Treg-depleted populations increased proliferation of both populations to either SEA or SWAP. These studies demonstrate that Treg appear to produce much of the antigen-stimulated IL-10, but other cell types or subsets of Treg may produce much of the TGF-β. The elevated levels of Treg seen in chronic schistosomiasis appear functional and involve IL-10 and TGF-β in antigen-specific immunoregulation perhaps leading to regulation of immunopathology and/or possibly decreased immunoprotective responses.

• • Risk Factors for Mortality in Children Hospitalized with Severe Malaria in Northern Zambia: A Retrospective Case–Control Study

    Authors: Matthew M. Ippolito, Luc K. Kamavu, Jean-Bertin Kabuya, Catherine Tente, Edward Chileshe, McBerth Wapachole, Philip E. Thuma, Mbanga Muleba, Mike Chaponda, Modest Mulenga, William J. Moss and for the Southern and Central Africa International Centers of Excellence for Malaria Research

    Available online: 23 April 2018

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    Malaria remains a public health crisis in areas where it has resisted control efforts. In Nchelenge District, a high- transmission area in northern Zambia, malaria accounts for more than one-third of pediatric hospitalizations and nearly one-half of hospital deaths in children. To identify risk factors for death due to malaria, we conducted a retrospective, time-matched case–control study of 126 children hospitalized with malaria who died (cases) and 126 children who survived (controls). There were no differences in age, gender, hemoglobin concentration, or prevalence of severe anemia between cases and controls. Children who died were more likely to come from villages located at greater distances from the hospital than children who survived (median 13.5 versus 3.2 km). Each additional kilometer of distance from the hospital increased the odds of death by 4% (odds ratio 1.04, 95% confidence interval 1.01–1.07, P < 0.01). Extent of anemia and admission during periods when blood was unavailable for transfusion were associated with early death (P ≤ 0.03). Delays in initiation of treatment of severe malaria contribute to the increased odds of death in children referred from more distant health centers, and might be mitigated by transportation improvements, capacity at rural health posts to administer treatment before transfer, hospital triage systems that minimize time to treatment, and reliable blood product stores at referral hospitals.

• • Seizures as a Complication of Congenital Zika Syndrome in Early Infancy

    Authors: Jamary Oliveira-Filho, Ridalva Felzemburgh, Federico Costa, Nivison Nery Jr.,, Adriana Mattos, Daniele F. Henriques, Albert I. Ko and for the Salvador Zika Response Team

    Available online: 23 April 2018

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    Zika virus transmission in Brazil was linked to a large outbreak of microcephaly but less is known about longer term anthropometric and neurological outcomes. We studied a cohort of infants born between October 31, 2015, and January 9, 2016, in a state maternity hospital, followed up for 101 ± 28 days by home visits. Microcephaly (< 2 standard deviations, Intergrowth standard) occurred in 62 of 412 (15%) births. Congenital Zika syndrome (CZS) was diagnosed in 29 patients. Among CZS patients, we observed a significant gain in anthropometric measures (P < 0.001) but no significant gain in percentile for these measures. The main neurological outcome was epilepsy, occurring in 48% of infants at a rate of 15.6 cases per 100 patient-months, frequently requiring multiple anti-seizure medications. The cumulative fatality rate was 7.4% (95% confidence interval: 2.1–23.4%). Health-care professionals should be alerted on the high risk of epilepsy and death associated with CZS in early infancy and the need to actively screen for seizures and initiate timely treatment.

• • Amoxicillin Quality and Selling Practices in Urban Pharmacies and Drug Stores of Blantyre, Malawi

    Authors: Ibrahim Chikowe, Sarah L. Bliese, Samuel Lucas and Marya Lieberman

    Available online: 23 April 2018

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    This study evaluated a newly developed paper analytical device (PAD) for screening amoxicillin samples in Blantyre urban townships. Covert shoppers attempted to buy amoxicillin from a geographically stratified selection of private pharmacies (N = 22 out of 26) and drug stores (N = 23 out of 103) in the township area. According to the PAD results, all 42 samples obtained by the shoppers contained amoxicillin and none contained suspicious filler materials. Next, the products were assayed using high-performance liquid chromatography. Consistent with the PAD results, all samples contained the correct amount of amoxicillin with no unexpected ingredients. However, one sample was purchased as amoxicillin and contained that ingredient, but was packaged in capsules that are normally used to package ampicillin. Almost every sample failed a simple packaging analysis. Nine in 10 samples were missing their original packaging and/or inserts (52.4% repackaged capsules and 35.7% repackaged blister packs). Only 33.3% of the packages had expiry dates, 16.7% had batch numbers, and 47.6% had the manufacturer’s name. Dispensing practices were likewise unsatisfactory. Ninety-five percentage of the sellers sold the amoxicillin without a prescription, even though this medicine is regulated as prescription-only in Malawi. Although the chemical analysis showed that amoxicillin quality was good, our market survey revealed poor adherence to prescription-only medicine dispensing of antibiotics, which threatens antimicrobial stewardship efforts. Furthermore, the wide prevalence of repackaging deprives medicines of important information needed during patient’s use, regulatory investigations, and pharmacovigilance reporting.

• • 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.

• • Case Report: Ocular Microsporidiosis: Case in a Patient Returning from India and Review of the Literature

    Authors: Jordan Leroy, Marjorie Cornu, Anne-Sophie Deleplancque, Aldert Bart, Séverine Loridant, Emilie Fréalle, Emmanuel Dutoit, Olivier Gaillot, Tom van Gool, François Puisieux, Pierre Labalette and Boualem Sendid

    Available online: 23 April 2018

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    Microsporidia are protists close to the kingdom of fungi that may cause eye infections. Most cases are reported in Asia and affect both immunocompromised and immunocompetent patients. Here, we report a rare case of microsporidial keratoconjunctivitis in an immunocompetent French patient 3 weeks after returning from India. In our patient, Weber trichrome staining of conjunctival scrapings revealed rounded elements approximately 1–3 μm in size. Conventional PCR analysis by ribosomal RNA subunit sequencing showed 100% identity with Vittaforma corneae. Treatment by corneal debridement combined with fluoroquinolone eye drops allowed complete resolution of the lesions. Although rare, ocular microsporidiosis should be investigated in a patient who is native to Asia or has returned from an endemic area and presents with keratoconjunctivitis of undetermined etiology.

• • Bunyavirus Taxonomy: Limitations and Misconceptions Associated with the Current ICTV Criteria Used for Species Demarcation

    Authors: Bradley J. Blitvich, Barry J. Beaty, Carol D. Blair, Aaron C. Brault, Gerhard Dobler, Michael A. Drebot, Andrew D. Haddow, Laura D. Kramer, Angelle Desiree LaBeaud, Thomas P. Monath, Eric C. Mossel, Kenneth Plante, Ann M. Powers, Robert B. Tesh, Michael J. Turell, Nikos Vasilakis and Scott C. Weaver

    Available online: 23 April 2018

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    The International Committee on Taxonomy of Viruses (ICTV) has implemented numerous changes to the taxonomic classification of bunyaviruses over the years. Whereas most changes have been justified and necessary because of the need to accommodate newly discovered and unclassified viruses, other changes are a cause of concern, especially the decision to demote scores of formerly recognized species to essentially strains of newly designated species. This practice was first described in the seventh taxonomy report of the ICTV and has continued in all subsequent reports. In some instances, viruses that share less than 75% nucleotide sequence identity across their genomes produce vastly different clinical presentations, possess distinct vector and host associations, have different biosafety recommendations, and occur in nonoverlapping geographic regions are classified as strains of the same species. Complicating the matter is the fact that virus strains have been completely eliminated from ICTV reports; thus, critically important information on virus identities and their associated biological and epidemiological features cannot be readily related to the ICTV classification. Here, we summarize the current status of bunyavirus taxonomy and discuss the adverse consequences associated with the reclassification and resulting omission of numerous viruses of public health importance from ICTV reports. As members of the American Committee on Arthropod-borne Viruses, we encourage the ICTV Bunyavirus Study Group to reconsider their stance on bunyavirus taxonomy, to revise the criteria currently used for species demarcation, and to list additional strains of public and veterinary importance.

• • Necrotizing Pneumonia Caused by Chromobacterium violaceum Soil Bacterium: Report of a Rare Human Pathogen Causing Disease in a Previously Undiagnosed Immunodeficient Child

    Authors: Alean Frawley, Lauren Powell, John R. McQuiston, Christopher A. Gulvik and Rodolfo E. Bégué

    Available online: 23 April 2018

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    Chromobacterium violaceum is a rare, potentially serious pathogen. Most clinicians have no experience with its clinical appearance or treatment. We describe a case of a child presenting with necrotizing pneumonia caused by C. violaceum. We describe case complexities, including the need for a multidisciplinary approach to diagnosis and treatment.

• • Gametocyte Development and Carriage in Ghanaian Individuals with Uncomplicated Plasmodium falciparum Malaria

    Authors: Bismarck Dinko, Felix Ansah, Comfort Agyare-Kwabi, Senyo Tagboto, Linda Eva Amoah, Britta C. Urban, Colin J. Sutherland, Gordon A. Awandare, Kim C. Williamson, Fred N. Binka and Kirk W. Deitsch

    Available online: 23 April 2018

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    Plasmodium falciparum gametocytes develop over 9–12 days while sequestered in deep tissues. On emergence into the bloodstream, they circulate for varied amounts of time during which certain host factors might influence their further development. We aimed to evaluate the potential association of patient clinical parameters with gametocyte development and carriage via in vivo methods. Seventy-two patients were enrolled from three hospitals in the Volta region of Ghana in 2016. Clinical parameters were documented for all patients, and gametocyte prevalence by microscopy was estimated at 12.5%. By measuring RNA transcripts representing two distinct gametocyte developmental stages using reverse transcriptase quantitative PCR (RT-qPCR), we obtained a more precise estimate of gametocyte carriage while also inferring gametocyte maturation. Fifty-three percent of the study participants harbored parasites expressing transcripts of the immature gametocyte-specific gene (PF3D7_1477700), whereas 36% harbored PF3D7_1438800 RNA-positive parasites, which is enriched in mid and mature gametocytes, suggesting the presence of more immature stages. Linear logistic regression showed that patients older than 5 years but less than 16 years were more likely to carry gametocytes expressing both PF3D7_1477700 and PF3D7_1438800 compared with younger participants, and gametocytemia was more likely in mildly anemic individuals compared with those with severe/moderate anemia. These data provide further evidence that a greater number of malaria patients harbor gametocytes than typically estimated by microscopy and suggest a possible association between age, fever, anemia, and gametocytemia.

• • Intraventricular Neurocysticercosis: Experience and Long-Term Outcome from a Tertiary Referral Center in the United States

    Authors: Theodore E. Nash, JeanAnne M. Ware and Siddhartha Mahanty

    Available online: 23 April 2018

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    Ventricular involvement in neurocysticercosis (NCC), a common serious manifestation of NCC, has distinct clinical presentations, complications, and treatments primarily because of partial or complete obstruction of the cerebrospinal fluid (CSF) flow by Taenia solium cysts. We review the clinical course, treatments, and long-term outcomes in 23 of 121 (19.0%) total NCC patients with ventricular cysts referred to the National Institutes of Health from 1985 to the October 2017. Patients had a median age of 31.8 (range: 22.4–52.6 years), were 60.9% male, diagnosed a median of 6.5 years (range: 0.17–16 years) after immigration, and were followed for a median of 3.6 years (range: 0.1–30.5 years). Other forms and manifestations of NCC were present in 73.9% (17/23). The fourth ventricle was involved in a majority (15/23, 65.2%) resulting in hydrocephalus (73.9%), ventriculitis, and periventricular edema (7/23, 30.4%). Cystectomy was accomplished in 60.9%, usually by removal of a fourth ventricular cyst through a suboccipital craniotomy. Nonresectable cysts were treated medically. Ventriculoperitoneal shunts were inserted in 43.5% (10/23) and failed in four, three from infection. Other complications included surgically induced injuries (4/23, 17.4%) and entrapment of a lateral ventricle (2/23, 8.7%). Despite a common severe early course, 90.9% (20/22) stabilized without recurrence, 15% (3/20) complained of mild-to-moderate neurological complaints, and 15% (3/20) were significantly disabled. Four patients who underwent removal of ventricular cysts without significant other NCC and who received with no cysticidal treatment became CSF cestode antigen negative without recurrence indicating that after successful extraction of cysts, additional cysticidal treatment may not be needed.

• • Burden of Influenza in Less Than 5-Year-Old Children Admitted to Hospital with Pneumonia in Developing and Emerging Countries: A Descriptive, Multicenter Study

    Authors: Cédric Dananché, Valentina Sánchez Picot, Thomas Bénet, Mélina Messaoudi, Monidarin Chou, Jianwei Wang, Jean-William Pape, Shally Awasthi, Ashish Bavdekar, Mala Rakoto-Andrianarivelo, Mariam Sylla, Pagbajabyn Nymadawa, Graciela Russomando, Florence Komurian-Pradel, Hubert Endtz, Gláucia Paranhos-Baccalà, Philippe Vanhems and on behalf of the Pneumonia GABRIEL Network

    Available online: 16 April 2018

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    This descriptive 4-year study reports the proportion of detection of influenza viruses in less than 5-year-old children hospitalized for pneumonia in eight developing and emerging countries and describes clinical and microbiological characteristics of influenza-related pneumonia cases. Hospitalized children presenting radiologically confirmed pneumonia aged 2–60 months were prospectively enrolled in this observational standardized study. Mean proportion of isolated influenza virus was 9.7% (95% confidence interval: 7.9–11.8%) among 888 pneumonia children analyzed, with moderate heterogeneity between countries—ranging from 6.2% in Cambodia to 18.8% in Haiti. The clinical characteristics of children with influenza-related pneumonia were not substantially different from those of other pneumonia cases. Influenza A H1N1-related pneumonia cases appeared as more severe than pneumonia cases related to other strains of influenza. Streptococcus pneumoniae was detected more often in blood samples from influenza-related cases than in those without detected influenza viruses (19.7% versus 9.5%, P = 0.018). Influenza-related pneumonia is frequent among children less than 5 years old with pneumonia, living in developing and emerging countries. Influenza might be a frequent etiologic agent responsible for pneumonia or a predisposing status factor for pneumococcal-related pneumonia in this population.

• • Congenital Toxoplasmosis in Tunisia: Prenatal and Neonatal Diagnosis and Postnatal Follow-up of 35 Cases

    Authors: Boudaouara Yosr, Aoun Karim, Maatoug Rania, Souissi Olfa, Bouratbine Aïda and Ben Abdallah Rym

    Available online: 16 April 2018

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    Congenital toxoplasmosis (CT) results from transplacental passage of Toxoplasma gondii to the fetus during acute maternal infection. Our study aims to report clinical and biological patterns of 35 cases of CT diagnosed at the department of the Parasitology of the Pasteur Institute of Tunis and to access the performance of prenatal and early postnatal diagnosis techniques. Serological screening of maternal infection was performed by Immunoglobulin (Ig) M and IgG detection and IgG avidity determination. Prenatal diagnosis was based on both Toxoplasma DNA detection in the amniotic fluid and monthly ultrasound examinations. PCR analysis on amniotic fluid, performed only in 15 cases, detected Toxoplasma’s DNA in five cases (33.3%). Ultrasound examination did not reveal any morphological abnormalities. Thirty newborns had serological criteria of Toxoplasma infection. Congenital toxoplasmosis diagnosis was confirmed in 23 cases (76.6%) by immunoblot. Among the 35 born-infants, five (14.3%) were symptomatic: three had chorioretinitis at the first clinical ocular examination, one had neurological symptoms (seizures) with positive parasite DNA in cerebral spinal fluid, and one had both ophthalmological and neurological damages— chorioretinitis and intracranial calcifications in the computed tomography scan. Thirty-four of 35 infected children were treated with pyrimethamine–sulfadiazine combination. Four (11.7%) of the treated infants showed abnormal hematological values because of the treatment side effect. Serological rebound was observed in seven infants. A screening program and a diagnostic algorithm in pregnant women should be implemented in Tunisia to improve the follow-up of seronegative ones and to prevent CT cases.

• • Causal Beliefs Affect Treatment Practices and Preferences for Neonatal Danger Signs in Northwest Ethiopia: A Qualitative Study

    Authors: Tariku Nigatu Bogale, Abebaw Gebeyehu Worku, Alemayehu Yalew, Gashaw Andargie Biks and Zemene Tigabu Kebede

    Available online: 16 April 2018

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    This study was conducted to explore the experiences of community members, particularly mothers, concerning their beliefs about the causes, treatment practices, and preferences for WHO-defined neonatal danger signs in northwest Ethiopia. A phenomenological qualitative study was conducted in three districts of north Gondar Zone, Amhara region, Ethiopia, from March 10 to 28, 2016. Twelve focus group discussions were conducted involving 98 individuals. In-depth interviews were conducted with six health extension workers and 30 women who were either pregnant or who delivered in the past 6 months. Six subthemes emerged explaining the causes of neonatal danger signs. The causes varied from danger sign to danger sign and from person to person. Most of the perceived causes of danger signs in neonates do not align with the current biomedical science. Causal assumptions and perceived seriousness of danger signs influenced treatment practices and preferences. Four subthemes also emerged for treatment practices and preferences. In some cases, respondents indicated that non-biomedical sources of treatment were superior in outcome compared with biomedical treatment options. Unsatisfactory outcomes were mentioned as major reasons to opt for treatments from non-biomedical sources. Religious and cultural reasons were reported to be major impediments for treatment seeking for newborn danger signs. There is an urgent need to introduce or expand locally modified program interventions, such as community-based newborn care, to educate the community on the causes of neonatal danger signs and the need for prompt care seeking from qualified providers.

• • Barriers to Participation in a Community-Based Program to Control Transmission of Taenia solium in Peru

    Authors: Michelle Beam, Angela Spencer, Lauralee Fernandez, Ruth Atto, Claudio Muro, Percy Vilchez, Ricardo Gamboa, Sandra Olaya, Viterbo Ayvar, Armando E. Gonzalez, Hector H. Garcia, Seth E. O’Neal and for The Cysticercosis Working Group in Peru

    Available online: 16 April 2018

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    Infection of the brain with Taenia solium larvae (neurocysticercosis) is a leading cause of preventable epilepsy worldwide. Effective and sustainable strategies to control parasite transmission in rural endemic communities are needed to prevent the disease. Surveillance and targeted intervention around infected pigs (ring control strategy) have been shown to be effective when carried out by research teams. However, this strategy has not been implemented or tested as a community-based program. In this small trial in northern Peru, eight villages were randomly assigned to community-led surveillance and treatment (five villages, 997 residents) or control (three villages, 1,192 residents). In intervention villages, community-led surveillance and reporting were promoted by community health workers, radio advertisement, and school and household education. Each suspected pig infection was verified, with confirmed cases resulting in treatment with niclosamide for taeniasis and oxfendazole for pigs in clusters of homes nearby. No incentives beyond human and pig treatment were offered. Control villages received basic disease education but no treatment intervention in response to reports. Despite 14 case reports, community-based replication of ring control strategy did not replicate prior results. After 12 months, there was no change in seroincidence in intervention villages between the baseline and study end, and no difference compared with control villages. There was no difference in prevalence of taeniasis or porcine cysticercosis at study end. Community members described lack of knowledge as the main reason for not reporting infected pigs. Further exploration of methods to transfer ring strategy and other control interventions for cysticercosis to the community is needed.

• • Analysis of Health-Care Charges in Murine Typhus: Need for Improved Clinical Recognition and Diagnostics for Acute Disease

    Authors: Rahat F. Vohra, David H. Walker and Lucas S. Blanton

    Available online: 09 April 2018

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    Murine typhus, caused by Rickettsia typhi, is an undifferentiated febrile illness with no available rapid and sensitive diagnostic assay for use during early disease. We aimed to compare the health-care charges in those diagnosed with murine typhus to those with influenza, a febrile illness with an available rapid diagnostic test. A comparison of health-care–associated charges at the University of Texas Medical Branch at Galveston demonstrated a median of $817 for influenza versus $16,760 for murine typhus (P < 0.0001). Median laboratory ($184 versus $3,254 [P < 0.0001]) and imaging charges ($0 versus $514 [P < 0.0001]) were also higher in those with murine typhus. Those receiving at least one imaging study during their illness were greater in the murine typhus group (91.3% versus 20.3%) (P < 0.0001). The median time needed to establish a confirmed or presumptive diagnosis was 2 days for influenza compared with 9 days for murine typhus (P < 0.0001). The median number of health-care encounters was greater for those with murine typhus (2 versus 1) (P < 0.0001). Eleven patients (15.9%) with influenza were hospitalized as a result of their illness compared with 16 (69.6%) with murine typhus (P < 0.0001). The estimated mortality based on disease severity at presentation by APACHE II scoring was similar in the two groups—both had a median 4% mortality risk (P = 0.0893). These results highlight the need for improved clinical recognition and diagnostics for acute rickettsioses such as murine typhus.

• • An Acarological Risk Model Predicting the Density and Distribution of Host-Seeking Ixodes scapularis Nymphs in Minnesota

    Authors: Tammi L. Johnson, Karen A. Boegler, Rebecca J. Clark, Mark J. Delorey, Jenna K. H. Bjork, Frances M. Dorr, Elizabeth K. Schiffman, David F. Neitzel, Andrew J. Monaghan and Rebecca J. Eisen

    Available online: 09 April 2018

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    Ixodes scapularis is the vector of at least seven human pathogens in Minnesota, two of which are known to cause Lyme disease (Borrelia burgdorferi sensu stricto and Borrelia mayonii). In Minnesota, the statewide incidence of Lyme disease and other I. scapularis–borne diseases and the geographic extent over which cases have been reported have both increased substantially over the last two decades. These changes correspond with an expanding distribution of I. scapularis over a similar time frame. Because the risk of exposure to I. scapularis–borne pathogens is likely related to the number of ticks encountered, we developed an acarological risk model predicting the density of host-seeking I. scapularis nymphs (DON) in Minnesota. The model was informed by sampling 81 sites located in 42 counties in Minnesota. Two main foci were predicted by the model to support elevated densities of host-seeking I. scapularis nymphs, which included the seven-county Minneapolis-St. Paul metropolitan area and counties in northern Minnesota, including Lake of the Woods and Koochiching counties. There was substantial heterogeneity observed in predicted DON across the state at the county scale; however, counties classified as high risk for I. scapularis–borne diseases and counties with known established populations of I. scapularis had the highest proportion of the county predicted as suitable for host-seeking nymphs (≥ 0.13 nymphs/100 m2). The model provides insight into areas of potential I. scapularis population expansion and identifies focal areas of predicted suitable habitat within counties where the incidence of I. scapularis–borne diseases has been historically low.

• • Prevalence of Depressive Symptoms and Related Risk Factors among Patients with Tuberculosis in China: A Multistage Cross-Sectional Study

    Authors: Yanhong Gong, Shijiao Yan, Lei Qiu, Shengchao Zhang, Zuxun Lu, Yeqing Tong, Pengqian Fang and Xiaoxv Yin

    Available online: 09 April 2018

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    Poor mental health among tuberculosis (TB) patients affects not only their compliance with treatments but also their daily lives. Few studies in China have evaluated depressive symptoms among TB patients. The present study aimed to determine the prevalence of depressive symptoms and its associated risk factors among Chinese TB patients. A total of 1,342 TB patients were recruited using a multistage sampling method and interviewed using a structured questionnaire. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Multinomial logistic regression analysis was performed to identify risk factors of depressive symptoms. Of the 1,342 participants included in this study, 48.0% had depressive symptoms. Of these, 34.8% and 13.2% had mild and moderate-to-severe depressive symptoms, respectively. Factors associated with depressive symptoms included family dysfunction, TB-related stigma, poor doctor–patient communication, and lack of knowledge about TB. Depressive symptoms are common among TB patients in China. Efforts of government and stakeholders in the development of relevant policy documents to prevent stigma and create social support for TB patients are necessary. This would not only promote their mental health but also improve their compliance with treatments.

• • Parapoxvirus Infections in the Country of Georgia: A Case Series

    Authors: Giorgi Chakhunashvili, Bradley F. Carlson, Laura Johnson, Ekaterine Khmaladze, Davit Tsaguria, Mari Gavashelidze, Khatuna Zakhashvili, Paata Imnadze and Matthew L. Boulton

    Available online: 09 April 2018

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    Infections caused by viruses of the parapoxvirus (PPV) genus, including orf and pseudocowpox viruses, are frequently seen in both humans and animals in many regions of the world. These infections are often misdiagnosed or neglected because of the lack of clinician awareness, inadequate diagnostic capacity, and their relatively mild disease presentation, which may result in affected individuals not seeking medical attention. Although PPV infections should be routinely considered in patients with cutaneous lesions, especially in those who have occupational exposure to farm animals, they are often excluded from the differential diagnosis because they are not perceived as serious, resulting in underestimation of the burden of disease. Since 2014, significant enhancements to Georgia’s epidemiologic and laboratory capacity have made PPV surveillance and detection possible. In this study, we present information on 27 confirmed cases of PPV infection reported to Georgia’s national surveillance system from January 2016 through January 2017.

• • Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review

    Authors: Gyem Tshering, Palden Wangyel Dorji, Wanna Chaijaroenkul and Kesara Na-Bangchang

    Available online: 09 April 2018

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    Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical settings.

• • Type I Interferon Receptor Variants in Gene Regulatory Regions are Associated with Susceptibility to Cerebral Malaria in Malawi

    Authors: Catherine Manix Feintuch, Archana Tare, Lucas Cusumano, Jacqueline Benayoun, Seungjin Ryu, Alick Sixpence, Karl Seydel, Miriam Laufer, Terrie Taylor, Yousin Suh and Johanna P. Daily

    Available online: 09 April 2018

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    Cerebral malaria (CM) remains an important cause of morbidity and mortality. Risk for developing CM partially depends on host genetic factors, including variants encoded in the type I interferon (IFN) receptor (IFNAR1). Type I IFNs bind to IFNAR1 resulting in increased expression of IFN responsive genes, which modulate innate and adaptive immune responses. To comprehensively study IFNAR1 genetic variant associations in Malawians with CM or uncomplicated malaria, we used a tag SNP approach, based on the HapMap Yoruba in Ibadan, Nigeria, population database. We identified three novel (rs914142, rs12626750, and rs1041867) and one previously published (Chr21:34696785 [C > G]) IFNAR1 variants to be associated with CM. Some of these variants are in gene regulatory regions. Chr21:34696785 (C > G) is in a region encoding histone modifications and transcription factor–binding sites, which suggests gene regulatory activity. Rs12626750 is predicted to bind ELAV-like RNA-binding protein 1, an RNA-binding protein which can increase the type I IFN response. Furthermore, we examined these variants in an expression quantitative trait loci database and found that a protective variant, rs914142, is associated with lower expression of IFNAR1, whereas the CM-associated variant rs12626750 was associated with increased IFNAR1 expression, suggesting that activation of the type I IFN pathway may contribute to pathogenesis of CM. Future functional studies of IFNAR1 variants are now needed to clarify the role of this pathway in severe malarial diseases.

• • A Comparison of Patients’ Local Conceptions of Illness and Medicines in the Context of C-Reactive Protein Biomarker Testing in Chiang Rai and Yangon

    Authors: Yuzana Khine Zaw, Nutcha Charoenboon, Marco J. Haenssgen and Yoel Lubell

    Available online: 09 April 2018

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    Antibiotic resistance is not solely a medical but also a social problem, influenced partly by patients’ treatment-seeking behavior and their conceptions of illness and medicines. Situated within the context of a clinical trial of C-reactive protein (CRP) biomarker testing to reduce antibiotic over-prescription at the primary care level, our study explores and compares the narratives of 58 fever patients in Chiang Rai (Thailand) and Yangon (Myanmar). Our objectives are to 1) compare local conceptions of illness and medicines in relation to health-care seeking and antibiotic demand; and to 2) understand how these conceptions could influence CRP point-of-care testing (POCT) at the primary care level in low- and middle-income country settings. We thereby go beyond the current knowledge about antimicrobial resistance and CRP POCT, which consists primarily of clinical research and quantitative data. We find that CRP POCT in Chiang Rai and Yangon interacted with fever patients’ preexisting conceptions of illness and medicine, their treatment-seeking behavior, and their health-care experiences, which has led to new interpretations of the test, potentially unforeseen exclusion patterns, implications for patients’ self-assessed illness severity, and an increase in the status of the formal health-care facilities that provide the test. Although we expected that local conceptions of illness diverge from inbuilt assumptions of clinical interventions, we conclude that this mismatch can undermine the intervention and potentially reproduce problematic equity patterns among CRP POCT users and nonusers. As a partial solution, implementers may consider applying the test after clinical examination to validate rather than direct prescription processes.

• • Comparative Vector Competence of North American Culex pipiens and Culex quinquefasciatus for African and European Lineage 2 West Nile Viruses

    Authors: Hannah Romo, Anna Papa, Rebekah Kading, Rebecca Clark, Mark Delorey and Aaron C. Brault

    Available online: 09 April 2018

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    West Nile virus (WNV) is a mosquito-borne flavivirus that is phylogenetically separated into distinct lineages. Lineage 1 (L1) and lineage 2 (L2) encompass all WNV isolates associated with human and veterinary disease cases. Although L1 WNV is globally distributed, including North America, L2 WNV only recently emerged out of sub-Saharan Africa into Europe and Russia. The spread of L2 WNV throughout and beyond Europe depends, in part, on availability of competent vectors. The vector competence of mosquitoes within the Culex genus for WNV is well established for L1 WNV but less extensively studied for L2 WNV. Assessing the vector competence of North American Culex mosquitoes for L2 WNV will be critical for predicting the potential for L2 WNV emergence in North America. We address the vector competence of North American Culex pipiens and Culex quinquefasciatus for L2 WNV. Both mosquito species were highly competent for each of the L2 WNV strains assessed, but variation in infection, dissemination, and transmission was observed. An L2 WNV strain (NS10) isolated during the Greek outbreak in 2010 exhibited a reduced capacity to infect Cx. pipiens compared with other L2 WNV strains. In addition, a South African L2 WNV strain (SA89) displayed a significantly shorter extrinsic incubation period in Cx. quinquefasciatus compared with other L2 WNV strains. These results demonstrate that North American Culex mosquito species are competent vectors of African and European L2 WNV and that emergence of L2 WNV is unlikely to be hindered by poor competence of North American vectors.

• • Elevated Levels of Urinary 8-oxodG Correlate with Persistent Periductal Fibrosis after Praziquantel Treatment in Chronic Opisthorchiasis

    Authors: Chompunoot Wangboon, Puangrat Yongvanit, Watcharin Loilom, Raynoo Thanan, Chanika Worasith, Chatanun Eamudomkarn, Nittaya Chamadol, Eimorn Mairiang, Jiraporn Sithithaworn, Prasert Saichua, Banchob Sripa, Narong Khuntikeo, Jeffrey M. Bethony and Paiboon Sithithaworn

    Available online: 09 April 2018

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    Previous studies demonstrated that urinary 8-oxodG is a predictive biomarker for Opisthorchis viverrini (OV)–associated hepatobiliary disease (HBD) and cholangiocarcinoma (CCA). This study examined the effects of praziquantel treatment on the profile of urinary 8-oxodG in relation to HBD status. Infection with OV, levels of urinary 8-oxodG, and HBD status in terms of periductal fibrosis (PDF) assessed by abdominal ultrasonography (US) were monitored and compared in cohorts of participants in Khon Kaen, Thailand, before and 1 year after praziquantel treatment. Urinary 8-oxodG levels significantly decreased after treatment compared with the baseline level in OV-infected participants who had no HBD (PDF negative; PDF−ve) (N = 14). Levels of 8-oxodG were unchanged after treatment in OV-infected subjects (OV+ve) who had positive PDF (N = 52). Within the positive PDF (PDF+ve) group who became PDF−ve after treatment, there was no significant change in 8-oxodG levels between pre-and posttreatment (reversible PDF = 65.3%). In those who had persistent PDF+ve at both ultrasound sampling points, there was no significant difference in urinary 8-oxodG levels between pre- and posttreatment (persistent PDF = 34.6%). Based on a logistic regression model and receiver operation curve analysis, the increase of 8-oxodG levels was found to be associated with increasing risk of PDF. Measurement of urinary 8-oxodG and US increased the likelihood of discovering persistent PDF, which is a predictable condition for the patients at risk of OV-associated CCA. To identify high-risk individuals for CCA, it is useful to perform US in combination with urinary 8-oxodG measurement.

• • Zika Virus Outbreak, Barbados, 2015–2016

    Authors: Sadie J. Ryan, Catherine A. Lippi, Colin J. Carlson, Anna M. Stewart-Ibarra, Mercy J. Borbor-Cordova, Moory M. Romero, Shelly-Ann Cox, Roché Mahon, Adrian Trotman, Leslie Rollock, Marquita Gittens-St. Hilaire, Desmond King and Steven Daniel

    Available online: 09 April 2018

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    Barbados is a Caribbean island country of approximately 285,000 people, with a thriving tourism industry. In 2015, Zika spread rapidly throughout the Americas, and its proliferation through the Caribbean islands followed suit. Barbados reported its first confirmed autochthonous Zika transmission to the Pan American Health Organization in January 2016, a month before the global public health emergency was declared. After detection of suspected Zika cases on Barbados in 2015, 926 individuals were described as suspected cases, and 147 laboratory-confirmed cases were reported through December 2016, the end of the most recent epidemiological year. In this short report, we describe the epidemiological characteristics of 926 clinical case records that were originally suspected as cases of Zika, and which were subsequently sent for testing and confirmation; 147 were found positive for Zika, using RT-PCR methods, another 276 tested negative, and the remaining 503 were either pending results or still in the suspected category. Women were represented at about twice the rate of men in case records where gender was reported (71.9%), and confirmed cases (78.2%), and 19 of the confirmed positive cases were children under the age of 10.

• • Genomic Characterization and Seroprevalence Studies on Alphaviruses in Uruguay

    Authors: Analía Burgueño, Sandra Frabasile, Luis Adrián Díaz, Andrés Cabrera, María Belén Pisano, María Elisa Rivarola, Marta Contigiani and Adriana Delfraro

    Available online: 09 April 2018

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    Alphaviruses (Togaviridae) are arboviruses frequently associated with emerging infectious diseases. In this study, we aimed to investigate the presence of alphaviruses in Uruguay by detecting the viral genome in mosquitoes and neutralizing antibodies in equines. A total of 3,575 mosquitoes were analyzed for alphavirus genome detection. Serologic studies were performed on 425 horse sera by plaque reduction neutralization test (PRNT80) against Venezuelan equine encephalitis virus (VEEV) subtype IAB, Pixuna virus (PIXV), Rio Negro virus (RNV), western equine encephalitis virus (WEEV), and Madariaga virus (MADV). Mosquitoes belonging to six genera were captured and 82.9% were identified as Culex pipiens. Two Cx. pipiens pools collected in Fray Bentos and Las Toscas localities were alphavirus positive, and phylogenetic analyses showed that the sequences grouped into two different clusters: the lineage I of eastern equine encephalitis virus and RNV (VEEV complex), respectively. Plaque reduction neutralization test assays showed antibodies against strains of the VEEV complex, MADV, and WEEV. Rio Negro virus was the most geographically widespread virus, showing higher seroprevalences (up to 20%). Seroprevalences against VEEV IAB ranged between 4.6% and 13%; antibodies against PIXV, WEEV, and MADV were less frequent (3–4%). In conclusion, RNV exhibited the highest seroprevalence in horses, a wide geographical distribution, and viral genome was detected in Cx. pipiens mosquitoes. Madariaga virus had a low seroprevalence in equines, but an epizootic lineage typical of North America was detected in Cx. pipiens mosquitoes. Taken together, our results show that alphaviruses are present in Uruguay with variable occurrence and geographical distribution being a potential threat for human and equine health.

• • Babesia microti and Malaria Infection in Africa: A Pilot Serosurvey in Kilosa District, Tanzania

    Authors: Evan M. Bloch, Kasubi Mabula, Andrew Levin, Zakayo Mrango, Jerusha Weaver, Beatriz Munoz and Sheila K. West

    Available online: 09 April 2018

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    Babesia is a tick-borne intraerythrocytic parasite that is clinically and diagnostically similar to malaria parasite, conferring risk of misdiagnosis in areas where both parasites are endemic. Data on Babesia in humans in Africa are lacking, despite evidence that it is present in regional animal populations. Samples that were collected in November 2014 to July 2015 in Kilosa district, Tanzania, were evaluated for evidence of malaria and Babesia infection. Clinical data and laboratory samples (i.e., hemoglobin, rapid diagnostic testing [RDT] for malaria, peripheral blood smear, and dried blood spots) from a routine survey were available for analysis. Dried blood spots were tested using an investigational ELISA against Babesia microti. A total of 1,030 children aged 1 month to < 5 years were evaluated; 186 (18.1%) were malaria RDT positive, 180 (96.8%) of whom had peripheral smears reviewed; 70/180 (38.9%) were smear positive for parasites. The median (inter quartile range) and range of B. microti ELISA signal to cutoff (S/C) ratio was 0.10 (0.06–0.15) and 0.01–1.65, respectively; the S/C ratios were significantly higher in subjects ≥ 1 year as compared with those < 1 year old (P < 0.001). There was also a statistically significant association between a positive RDT for malaria and the Babesia S/C (median 0.09 versus 0.13 in RDT negative versus RDT positive, respectively; P < 0.001). The highest S/C ratios were disproportionately clustered in a few hamlets. The findings suggest that Babesia may be present in Kilosa district, Tanzania. However, serological cross-reactivity and false positivity, notably between Babesia and Plasmodium spp., cannot be definitively excluded and have implications for testing in other settings.

• • Environmental Enteropathy in Undernourished Pakistani Children: Clinical and Histomorphometric Analyses

    Authors: Sana Syed, Sunil Yeruva, Jeremy Herrmann, Anne Sailer, Kamran Sadiq, Najeeha Iqbal, Furqan Kabir, Kumail Ahmed, Shahida Qureshi, Sean R. Moore, Jerrold Turner and S. Asad Ali

    Available online: 02 April 2018

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    Despite nutrition interventions, stunting thought to be secondary to underlying environmental enteropathy (EE) remains pervasive among infants residing in resource-poor countries and remains poorly characterized. From a birth cohort of 380 children, 65 malnourished infants received 12 weeks of nutritional supplementation with ready-to-use therapeutic food (RUTF). Eleven children with insufficient response to RUTF underwent upper endoscopy with duodenal biopsies, which were compared with U.S., age-matched specimens for healthy, celiac disease, non-celiac villous atrophy, non-celiac intraepithelial lymphocytosis, and graft-versus-host disease patients. Of the 11 children biopsied, EE was found in 10 (91%) with one subject with celiac disease. Morphometry demonstrated decreased villus-to-crypt (V:C) ratios in EE relative to healthy and non-celiac lymphocytosis patients. Environmental enteropathy villus volumes were significantly decreased relative to healthy controls. In EE, average CD3+ cells per 100 epithelial cells and per 1,000 µm2 of lamina propria and the number of lamina propria CD20+ B-cell aggregates were increased relative to all other groups. Our results indicate that V:C ratios are reduced in EE but are less severe than in celiac disease. Environmental enteropathy intraepithelial and lamina propria T lymphocytosis is of greater magnitude than that in celiac disease. The increases in lamina propria B and T lymphocytes suggest that non-cytolytic lymphocytic activation may be a more prominent feature of EE relative to celiac disease. These results provide new insights into shared yet distinct histological and immunological features of EE and celiac disease in children.

• • Hospitalized Bacteremic Melioidosis in Rural Thailand; 2009–2013

    Authors: Anchalee Jatapai, Christopher J. Gregory, Somsak Thamthitiwat, Kittisak Tanwisaid, Saithip Bhengsri, Henry C. Baggett, Ornuma Sangwichian, Possawat Jorakate and John R. MacArthur

    Available online: 02 April 2018

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    Melioidosis incidence and mortality have reportedly been increasing in endemic areas of Thailand, but little population-based data on culture-confirmed Burkholderia pseudomallei infections exist. We provide updated estimates of melioidosis bacteremia incidence and in-hospital mortality rate using integration of two population-based surveillance databases in Nakhon Phanom, Thailand, since automated blood culture became available in 2005. From 2009 to 2013, 564 hospitalized bacteremic melioidosis patients were identified. The annual incidence of bacteremic melioidosis ranged from 14 to 17 per 100,000 persons, and average population mortality rate was 2 per 100,000 persons per year. In-hospital mortality rate declined nonsignificantly from 15% (15/102) to 13% (15/118). Of 313 (56%) bacteremic melioidosis patients who met criteria for acute lower respiratory infection and were included in the hospital-based pneumonia surveillance system, 65% (202/313) had a chest radiograph performed within 48 hours of admission; 46% (92/202) showed radiographic evidence of pneumonia. Annual incidence of bacteremic melioidosis with pneumonia was 2.4 per 100,000 persons (95% confidence intervals; 1.9–2.9). In-hospital death was more likely among bacteremic melioidosis patients with pneumonia (34%; 20/59) compared with non-pneumonia patients (18%; 59/321) (P-value = 0.007). The overall mortality could have been as high as 46% (257/564) if patients with poor clinical condition at the time of discharge had died. The continued high incidence of bacteremic melioidosis, pneumonia, and deaths in an endemic area highlights the need for early diagnosis and treatment and additional interventions for the prevention and control for melioidosis.

• • Survey to Identify Substandard and Falsified Tablets in Several Asian Countries with Pharmacopeial Quality Control Tests and Principal Component Analysis of Handheld Raman Spectroscopy

    Authors: Tomoko Kakio, Hitomi Nagase, Takashi Takaoka, Naoko Yoshida, Junichi Hirakawa, Susan Macha, Takashi Hiroshima, Yukihiro Ikeda, Hirohito Tsuboi and Kazuko Kimura

    Available online: 02 April 2018

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    The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market.

• • Clinical and Neurophysiological Features of Leprosy Patients with Neuropathic Pain

    Authors: Louise Mara Giesel, Izabela Jardim Rodrigues Pitta, Raquel Custódio Silveira, Lígia Rocha Andrade, Robson Teixeira Vital, José Augusto da Costa Nery, Mariana de Andrea Vilas Boas Hacker, Euzenir Nunes Sarno and Marcia Maria Jardim Rodrigues

    Available online: 02 April 2018

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    Neural pain is a frequent symptom in leprosy disease. There is a paucity of data regarding neural pain diagnostics resulting in common prescriptive errors when neuritis is confused with neuropathic or mixed nociceptive–neuropathic pain. The present study identified important demographic, clinical, and neurophysiological features of 42 leprosy neuropathy patients presenting neuropathic pain (NP). During routine evaluations, patients were selected asking if they had ever experienced neural pain. Data analyses of their pain characteristics, clinical examination results, and both the Douleur Neuropathique 4 Questionnaire and Hamilton Depression Scale scores were used to classify these patients. The most common word they used to describe the sensation of pain for 25 (60%) of these patients was “burning.” In the early stages of the disease and before leprosy diagnosis, 19 (45%) had already complained about NP and leprosy treatment was unable to prevent its occurrence in 15 (36%). Leprosy reactions, considered NP risk factors, occurred in 32 (76%) cases. Knowledge of typical NP characteristics could be used to develop more effective therapeutic approaches for a notoriously difficult-to-treat pain condition.

• • Validity of Time to Sputum Culture Conversion to Predict Cure in Patients with Multidrug-Resistant Tuberculosis: A Retrospective Single-Center Study

    Authors: Nafees Ahmad, Arshad Javaid, Afsar Khan Afridi, Anila Basit, Amer Hayat Khan, Izaz Ahmad and Muhammad Atif

    Available online: 02 April 2018

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    To evaluate the predictive value of time to sputum culture conversion (SCC) in predicting cure and factors associated with time to SCC and cure in multidrug-resistant tuberculosis (MDR-TB) patients, a retrospective study was conducted at programmatic management unit of drug resistant tuberculosis (TB), Peshawar. A total of 428 pulmonary MDR-TB patients enrolled at the study site from January 1, 2012 to August 31, 2014 were followed until treatment outcome was recorded. Survival analysis using Cox proportional hazards model and multivariate binary logistic regression were, respectively, used to identify factors associated with time to SCC and cure. A P value < 0.05 was considered statistically significant. Overall, 90.9% patients achieved SCC, and 76.9% were cured. Previous use of second-line drugs (SLDs) (hazard ratio [HR] = 0.637; 95% confidence interval [CI] = 0.429–0.947), ofloxacin resistance (HR = 0.656; 95% CI = 0.522–0.825) and lung cavitation (HR = 0.744; 95% CI = 0.595–0.931) were significantly associated with time to SCC. In predicting cure, sensitivities of SCC at 2, 4, and 6 months were 64.1% (95% CI = 58.69–69.32), 93.0% (95% CI = 89.69–95.52), and 97.6% (95% CI = 95.27–98.94), respectively, whereas specificities were 67.7% (95% CI = 57.53–76.73), 51.5% (95% CI = 41.25–61.68), and 44.4% (95% CI = 34.45–54.78), respectively. Furthermore, patients’ age of 41–60 (odds ratio [OR] = 0.202; 95% CI = 0.067–0.605) and > 60 years (OR = 0.051; 95% CI = 0.011–0.224), body weight > 40 kg (OR = 2.950; 95% CI = 1.462–5.952), previous SLD use (OR = 0.270; 95% CI = 0.097–0.789), lung cavitation (OR = 0.196; 95% CI = 0.103–0.371) and ofloxacin resistance (OR = 0.386; 95% CI = 0.198–0.749) were significantly associated with cure. Association of SCC with cure was substantially stronger at 6 months (OR = 32.10; 95% CI = 14.34–71.85) than at 4 months (OR = 14.13; 95% CI = 7.92–25.21). However in predicting treatment outcomes, the combined sensitivity and specificity of SCC at 4 months was comparable to SCC at 6 months. Patients with risk factors for delayed SCC were also at high risk of unsuccessful outcomes.

• • Internally Controlled, Multiplex Real-Time Reverse Transcription PCR for Dengue Virus and Yellow Fever Virus Detection

    Authors: Alejandra Rojas, Cheikh T. Diagne, Victoria D. Stittleburg, Alisha Mohamed-Hadley, Yvalena Arévalo de Guillén, Angel Balmaseda, Oumar Faye, Ousmane Faye, Amadou A. Sall, Eva Harris, Benjamin A. Pinsky and Jesse J. Waggoner

    Available online: 02 April 2018

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    The differential diagnosis of dengue virus (DENV) and yellow fever virus (YFV) infections in endemic areas is complicated by nonspecific early clinical manifestations. In this study, we describe an internally controlled, multiplex real-time reverse transcription PCR (rRT-PCR) for the detection of DENV and YFV. The DENV–YFV assay demonstrated specific detection and had a dynamic range of 2.0–8.0 log10 copies/μL of eluate for each DENV serotype and YFV. Clinical performance was similar to a published pan-DENV assay: 48/48 acute-phase samples from dengue cases were detected in both assays. For YFV detection, mock samples were prepared with nine geographically diverse YFV isolates over a range of concentrations. The DENV–YFV assay detected 62/65 replicates, whereas 54/65 were detected using a reference YFV rRT-PCR. Given the reemergence of DENV and YFV in areas around the world, the DENV–YFV assay should be a useful tool to narrow the differential diagnosis and provide early case detection.

• • Use of TaqMan Array Cards to Screen Outbreak Specimens for Causes of Febrile Illness in Tanzania

    Authors: Ahmed Abade, Rachel B. Eidex, Athanasia Maro, Jean Gratz, Jie Liu, Ireen Kiwelu, Buliga Mujaga, Maria Kelly, Blandina T. Mmbaga, James J. Gibson, Fausta Mosha and Eric R. Houpt

    Available online: 02 April 2018

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    We describe the deployment of a custom-designed molecular diagnostic TaqMan Array Card (TAC) to screen for 31 bacterial, protozoal, and viral etiologies in blood from outbreaks of acute febrile illness in Tanzania during 2015–2017. On outbreaks notified to the Tanzanian Ministry of Health, epidemiologists were dispatched and specimens were collected, transported to a central national laboratory, and tested by TAC within 2 days. This algorithm streamlined investigation, diagnosed a typhoid outbreak, and excluded dozens of other etiologies. This method is usable in-country and may be incorporated into algorithms for diagnosing outbreaks.

• • Molecular Markers of Plasmodium falciparum Drug Resistance in Parasitemic Pregnant Women in the Middle Forest Belt of Ghana

    Authors: Joseph Osarfo, Harry Tagbor, Pascal Magnussen and Michael Alifrangis

    Available online: 26 March 2018

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    Data on prevalence of antimalarial molecular resistance markers in pregnant women in Ghana is scarce. Prevalence of single nucleotide polymorphisms/haplotypes in the Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps genes was assessed in a cross-sectional study involving 200 pregnant women. Almost 90% of infections were wild type at the Pfcrt gene whereas the Pfmdr1 NFD mutant haplotype occurred in 43% of samples. Prevalence of Pfdhfr/Pfdhps quadruple mutation was 92.6% whereas Pfdfr/Pfdhps quintuple mutation with K540E was not observed. The study provides important updates of antimalarial resistance markers in Ghanaian pregnant women and suggests increased tolerance to one of the first-line treatment options in Ghana: artemether–lumefantrine. The data support the view that sulfadoxine–pyrimethamine is still efficacious for intermittent preventive treatment in Ghana, but the impact of increased doses on selection of mutations needs to be assessed. Continuing the surveillance of resistance markers is important to inform changes in antimalarial drug policy in pregnancy.

• • Yemen in a Time of Cholera: Current Situation and Challenges

    Author: Hesham M. Al-Mekhlafi

    Available online: 19 March 2018

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    Since early 2015, Yemen has been in the throes of a grueling civil war, which has devastated the health system and public services, and created one of the world’s worst humanitarian disasters. The country is currently facing a cholera epidemic the world’s largest on record, surpassing one million (1,061,548) suspected cases, with 2,373 related deaths since October 2016. Cases were first confirmed in Sana’a city and then spread to almost all governorates except Socotra Island. Continued efforts are being made by the World Health Organization and international partners to contain the epidemic through improving water, sanitation and hygiene, setting up diarrhea treatment centers, and improving the population’s awareness about the disease. The provision of clean water and adequate sanitation is imperative as an effective long-term solution to prevent the further spread of this epidemic. Cholera vaccination campaigns should also be conducted as a preventive measure.

• • Insights into the Performance of SD Bioline Malaria Ag P.f/Pan Rapid Diagnostic Test and Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in Madagascar

    Authors: Nigani Willie, Rajeev K. Mehlotra, Rosalind E. Howes, Tovonahary A. Rakotomanga, Stephanie Ramboarina, Arsène C. Ratsimbasoa and Peter A. Zimmerman

    Available online: 19 March 2018

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    Plasmodium falciparum histidine-rich protein 2 (PfHRP2) forms the basis of many current malaria rapid diagnostic tests (RDTs). However, the parasites lacking part or all of the pfhrp2 gene do not express the PfHRP2 protein and are, therefore, not identifiable by PfHRP2-detecting RDTs. We evaluated the performance of the SD Bioline Malaria Ag P.f/Pan RDT together with pfhrp2 variation in Madagascar. Genomic DNA isolated from 260 patient blood samples were polymerase chain reaction (PCR)–amplified for the parasite 18S rRNA and pfhrp2 genes. Post-PCR ligation detection reaction-fluorescent microsphere assay (LDR-FMA) was performed for the identification of parasite species. Plasmodium falciparum histidine-rich protein 2 amplicons were sequenced. Polymerase chain reaction diagnosis of patient samples showed that 29% (75/260) were infected and P. falciparum was present in 95% (71/75) of these PCR-positive samples. Comparing RDT and P. falciparum detection by LDR-FMA, eight samples were RDT negative but P. falciparum positive (false negatives), all of which were pfhrp2 positive. The sensitivity and specificity of the RDT were 87% and 90%, respectively. Seventy-three samples were amplified for pfhrp2, from which nine randomly selected amplicons were sequenced, yielding 13 sequences. Amplification of pfhrp2, combined with RDT analysis and P. falciparum detection by LDR-FMA, showed that there was no indication of pfhrp2 deletion. Sequence analysis of pfhrp2 showed that the correlation between pfhrp2 sequence structure and RDT detection rates was unclear. Although the observed absence of pfhrp2 deletion from the samples screened here is encouraging, continued monitoring of the efficacy of the SD Bioline Malaria Ag P.f/Pan RDT for malaria diagnosis in Madagascar is warranted.

• • Mosquito-Borne Human Viral Diseases: Why Aedes aegypti?

    Author: Jeffrey R. Powell

    Available online: 19 March 2018

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    Although numerous viruses are transmitted by mosquitoes, four have caused the most human suffering over the centuries and continuing today. These are the viruses causing yellow fever, dengue, chikungunya, and Zika fevers. Africa is clearly the ancestral home of yellow fever, chikungunya, and Zika viruses and likely the dengue virus. Several species of mosquitoes, primarily in the genus Aedes, have been transmitting these viruses and their direct ancestors among African primates for millennia allowing for coadaptation among viruses, mosquitoes, and primates. One African primate (humans) and one African Aedes mosquito (Aedes aegypti) have escaped Africa and spread around the world. Thus it is not surprising that this native African mosquito is the most efficient vector of these native African viruses to this native African primate. This makes it likely that when the next disease-causing virus comes out of Africa, Ae. aegypti will be the major vector to humans.

• • Association between Severity of Liver Disease, Frequency of Helicobacter pylori Infection, and Degree of Gastric Lesion in Egyptian Patients with Hepatitis B Virus Infection

    Authors: Amal A. Mohamed, Amal A. Elshimy, Abir O. El Sadik, Elham Ezzat, Mona Nasar, Shereen S. M. Elshaer and Moataz M. Sayed

    Available online: 30 October 2017

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    The relationship between hepatitis B virus (HBV) infection, severity of liver disease, frequency of Helicobacter pylori infection, and degree of gastric lesions was not yet fully investigated in Egyptian patients. The present work was performed on 100 Egyptian patients with HBV from the National Hepatology and Tropical Medicine Institute and 70 healthy volunteers as control group. The participants were subjected to full medical history taking, clinical examination, and laboratory investigations. All patients were positive for HBV surface antigen (HBV sAg), HBV DNA, and negative for hepatitis C virus antibodies. The severity of the liver disease was assessed using Child–Pugh scoring system. Screening of all participants for H. pylori Ag in stool was performed. Biopsy specimens were taken from the gastric lesions of H. pylori-infected patients for histopathological examination. The mean age of the patients and control group were 34.9 and 33.4 years, respectively. The levels of the liver enzymes were statistically higher in HBV patients than the control group. Helicobacter pylori Ag in stool was detected in 45.7% of the control group, and a higher percentage (60%) was detected in the patients group. Chronic gastritis with glandular atrophy and metaplasia was found in 15.6% of patients of Child–Pugh A, 70% of Child–Pugh B, and 100% of Child–Pugh C. It could be concluded that the prognosis of the liver disease significantly influences the severity of the gastric pathology in H. pylori infection.

• • 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.

• • Dengue Virus Serotypes 1 and 2 Responsible for Major Dengue Outbreaks in Nepal: Clinical, Laboratory, and Epidemiological Features

    Authors: Shyam Prakash Dumre, Renu Bhandari, Geeta Shakya, Sanjay Kumar Shrestha, Mahamoud Sama Cherif, Prakash Ghimire, Chonticha Klungthong, In-Kyu Yoon, Kenji Hirayama, Kesara Na-Bangchang and Stefan Fernandez

    Available online: 31 July 2017

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    Dengue virus (DENV) is expanding toward previously nonendemic areas. DENV has recently been introduced in Nepal with limited information. We report the clinical features and serotype distribution of DENV in Nepal during the major outbreaks. A total of 1,215 clinical dengue cases at two major hospitals of central and western Nepal were investigated. Demographic, clinical, and laboratory parameters were recorded. Serum specimens were tested for DENV by IgM/IgG enzyme-linked immunosorbent assays (ELISAs) and reverse transcription polymerase chain reaction (RT-PCR). We confirmed DENV infection in 403 (33%) patients from 12 districts with an estimated case fatality rate of 1.5%. DENV infection was more common in adults (87%) and urban settings (74%). We detected all four serotypes but DENV-1 and -2 were mainly responsible for major outbreaks (92%). Overall, 60% of all DENV infections were secondary and 17% were severe dengue; both being more frequent among the DENV-2 infections. Rash, bleeding, abdominal pain, hepatomegaly, elevated liver enzymes, and thrombocytopenia were significantly more common in severe dengue compared with nonsevere infections. We also confirmed the expansion of dengue to hill urban areas (DENV-1 and -2), including the capital Kathmandu (altitude, 1,300 m) though > 90% cases were from southern plains. Differential clinical and laboratory features probably helps in clinical decisions. Multiple serotypes circulation and elevated secondary infections pose potential risk of severe outbreaks and deaths in the future. Therefore, a country with recent dengue introduction, like Nepal, urgently requires a systematic surveillance and appropriate control measures in place to respond any disastrous outbreaks.

• • Evaluation of Community-Directed Operation of Black Fly Traps for Entomological Surveillance of Onchocerca volvulus Transmission in the Madi-Mid North Focus of Onchocerciasis in Northern Uganda

    Authors: Denis Loum, Charles R. Katholi, Thomson Lakwo, Peace Habomugisha, Edridah M. Tukahebwa and Thomas R. Unnasch

    Available online: 31 July 2017

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    Entomological measures of transmission are important metrics specified by the World Health Organization to document the suppression and interruption of transmission of Onchocerca volvulus, the causative agent of onchocerciasis. These metrics require testing of large numbers of vector black flies. Black fly collection has relied on human landing collections, which are inefficient and potentially hazardous. As the focus of the international community has shifted from onchocerciasis control to elimination, replacement of human landing collections has become a priority. The Esperanza window trap (EWT) has shown promise as an alternative method for collection of Simulium damnosum s.l., the primary vector of O. volvulus in Africa. Here, we report the results of a community-based trial of the EWT in northern Uganda. Traps operated by residents were compared with human landing collections in two communities over 5 months. Three traps, when operated by a single village resident, collected over four times as many S. damnosum as did the two-men collection team. No significant differences were noted among the bait formulations. The results suggest that EWTs may be effectively operated by community residents and that the trap represents a viable alternative to human landing collections for entomological surveillance of O. volvulus transmission.

• • Case Report: Old World Mucosal Leishmaniasis: Report of Five Imported Cases to the Hospital for Tropical Diseases, London, United Kingdom

    Authors: Trupti A. Patel, Glenis K. Scadding, David E. Phillips and Diana N. Lockwood

    Available online: 24 July 2017

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    Old World species of Leishmania typically cause visceral and cutaneous leishmaniasis. Mucosal involvement is typically seen with infection by Leishmania species found in South America, usually after the healing of cutaneous leishmaniasis. We present five imported cases of mucosal leishmaniasis caused by Old World Mediterranean Leishmania infantum exclusively affecting the nasal mucosa or vocal cord. In only one case was there a recollection of a preceding cutaneous lesion compatible with cutaneous Leishmaniasis. Of significance was that four out of five cases were receiving local corticosteroids for chronic lung disorders and four were systemically immunosuppressed. This report highlights the importance of considering mucosal leishmaniasis in the differential diagnosis in those presenting with upper respiratory tract mucosal lesions with a relevant travel history to the Mediterranean and in whom malignancy has been excluded.