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The American Journal of Tropical Medicine and Hygiene - Online First
In order to provide our readers with timely access to new content, papers accepted by the American Journal of Tropical Medicine and Hygiene are posted online ahead of print publication. Papers that have been accepted for publication are peer-reviewed and copy edited but do not incorporate all corrections or constitute the final versions that will appear in the Journal. Final, corrected papers will be published online concurrent with the release of the print issue.
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Strengthening Mentoring in Low- and Middle-Income Countries to Advance Global Health Research: An Overview
Available online: 14 November 2018More LessMentoring is a proven path to scientific progress, but it is not a common practice in low- and middle-income countries (LMICs). Existing mentoring approaches and guidelines are geared toward high-income country settings, without considering in detail the differences in resources, culture, and structure of research systems of LMICs. To address this gap, we conducted five Mentoring-the-Mentor workshops in Africa, South America, and Asia, which aimed at strengthening the capacity for evidence-based, LMIC-specific institutional mentoring programs globally. The outcomes of the workshops and two follow-up working meetings are presented in this special edition of the American Journal of Tropical Medicine and Hygiene. Seven articles offer recommendations on how to tailor mentoring to the context and culture of LMICs, and provide guidance on how to implement mentoring programs. This introductory article provides both a prelude and executive summary to the seven articles, describing the motivation, cultural context and relevant background, and presenting key findings, conclusions, and recommendations.
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Conceptual Framework of Mentoring in Low- and Middle-Income Countries to Advance Global Health
Available online: 14 November 2018More LessAlthough mentoring is not a common practice in low- and middle-income countries (LMICs), there is a strong need for it. Conceptual frameworks provide the structure to design, study, and problem-solve complex phenomena. Following four workshops in South America, Asia, and Africa, and borrowing on theoretical models from higher education, this article proposes two conceptual frameworks of mentoring in LMICs. In the first model, we propose to focus the mentor–mentee relationship and interactions, and in the second, we look at mentoring activities from a mentees’ perspective. Our models emphasize the importance of an ongoing dynamic between the mentor and mentee that is mutually beneficial. It also emphasizes the need for institutions to create enabling environments that encourage mentorship. We expect that these frameworks will help LMIC institutions to design new mentoring programs, clarify expectations, and analyze problems with existing mentoring programs. Our models, while being framed in the context of global health, have the potential for wider application geographically and across disciplines.
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Global Health Research Mentoring Competencies for Individuals and Institutions in Low- and Middle-Income Countries
Available online: 14 November 2018More LessMentoring is beneficial to mentors, mentees, and their institutions, especially in low- and middle-income countries (LMICs), that are faced with complex disease burdens, skills shortages, and resource constraints. Mentoring in global health research can be enhanced by defining key competencies, to enable the skill set required for effective mentoring, determine training needs for local research mentors, and facilitate institutional capacity building to support mentors. The latter includes advocating for resources, institutional development of mentoring guidelines, and financial and administrative support for mentoring. Nine core global health research mentoring competencies were identified: maintaining effective communication; aligning expectations with reasonable goals and objectives; assessing and providing skills and knowledge for success; addressing diversity; fostering independence; promoting professional development; promoting professional integrity and ethical conduct; overcoming resource limitations; and fostering institutional change. The competencies described in this article will assist mentors to sharpen their cognitive skills, acquire or generate new knowledge, and enhance professional and personal growth and job satisfaction. Similarly, the proposed competencies will enhance the knowledge and skills of mentees, who can continue and extend the work of their mentors, and advance knowledge for the benefit of the health of populations in LMICs.
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Mentoring the Mentors: Implementation and Evaluation of Four Fogarty-Sponsored Mentoring Training Workshops in Low-and Middle-Income Countries
Available online: 14 November 2018More LessA growing body of evidence highlights the importance of competent mentoring in academic research. We describe the development, implementation, and evaluation of four regional 2-day intensive workshops to train mid- and senior-level investigators conducting public health, clinical, and basic science research across multiple academic institutions in low- and middle-income countries (LMICs) on tools and techniques of effective mentoring. Sponsored by the Fogarty International Center, workshops included didactic presentations, interactive discussions, and small-group problem-based learning and were conducted in Lima, Peru; Mombasa, Kenya; Bangalore, India; and Johannesburg, South Africa, from 2013 to 2016. Mid- or senior-level faculty from multiple academic institutions within each region applied and were selected. Thirty faculty from 12 South America–based institutions, 29 faculty from eight East Africa–based institutions, 37 faculty from 14 South Asia–based institutions, and 36 faculty from 13 Africa-based institutions participated, with diverse representation across disciplines, gender, and academic rank. Discussions and evaluations revealed important comparisons and contrasts in the practice of mentoring, and specific barriers and facilitators to mentoring within each cultural and regional context. Specific regional issues related to hierarchy, the post-colonial legacy, and diversity arose as challenges to mentoring in different parts of the world. Common barriers included a lack of a culture of mentoring, time constraints, lack of formal training, and a lack of recognition for mentoring. These workshops provided valuable training, were among the first of their kind, were well-attended, rated highly, and provided concepts and a structure for the development and strengthening of formal mentoring programs across LMIC institutions.
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The Evolution of Mentorship Capacity Development in Low- and Middle-Income Countries: Case Studies from Peru, Kenya, India, and Mozambique
Available online: 14 November 2018More LessFollowing the Fogarty International Center-supported “Mentoring the Mentors” workshops in South America, Africa, and Asia, approaches and guidelines for mentorship at institutions within these low- and middle-income country (LMIC) contexts, appropriate for the respective regional resources and culture, were implemented. Through the presentation of case studies from these three geographic regions, this article illustrates the institutional mentorship infrastructure before the workshop and the identified gaps used to implement strategies to build mentorship capacity at the Universidad Peruana Cayetano Heredia (Peru), Kenya Medical Research Institute (Kenya), Saint John’s Research Institute (India), and Eduardo Mondlane University (Mozambique). These case studies illustrate three findings: first, that mentorship programs in LMICs have made uneven progress, and institutions with existing programs have exhibited greater advancement to their mentoring capacity than institutions without formal programs before the workshops. Second, mentoring needs assessments help garner the support of institutional leadership and create local ownership. Third, developing a culture of mentorship that includes group mentoring activities at LMIC institutions can help overcome the shortage of trained mentors. Regardless of the stage of mentoring programs, LMIC institutions can work toward developing sustainable, culturally effective mentorship models that further the partnership of early career scientists and global health.
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Evaluating Academic Mentorship Programs in Low- and Middle-Income Country Institutions: Proposed Framework and Metrics
Available online: 14 November 2018More LessA growing number of low- and middle-income country (LMIC) institutions have developed and implemented formal programs to support mentorship. Although the individual-level benefits of mentorship are well established, such activities can also sustainably build institutional capacity, bridge inequities in health care, and catalyze scientific advancement. To date, however, evaluation of these programs remains limited, representing an important gap in our understanding about the impact of mentoring. Without rigorous and ongoing evaluation, there may be missed opportunities for identifying best practices, iteratively improving program activities, and demonstrating the returns on investment in mentorship. In this report, we propose a framework for evaluating mentorship programs in LMIC settings where resources may be constrained. We identify six domains: 1) mentor–mentee relationship, 2) career guidance, 3) academic productivity, 4) networking, 5) wellness, and 6) organizational capacity. Within each, we describe specific metrics and how they may be considered as part of evaluation plans. We emphasize the role of measurement and evaluation at the institutional level, so that programs may enhance their mentoring capacity and optimize the management of their resources. Although we advocate for a comprehensive approach to evaluation, we recognize that—depending on stage and relative maturity—some domains may be prioritized to address short- and medium-term program goals.
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Mentorship and Ethics in Global Health: Fostering Scientific Integrity and Responsible Conduct of Research
Available online: 14 November 2018More LessAddressing ethical issues through mentorship is key to encouraging scientific integrity and increasing research capacity. Across the global health arena, mentorship requires helping mentees understand and negotiate the regulatory aspects of research—which can substantially differ even between countries with similar resources. Mentorship support spans across the research framework from obtaining ethical approval and ensuring scientific integrity, to determining authorship and disseminating study results—providing multiple opportunities to model ethical behavior for mentees. The power imbalances between the global north and south in accessing funding resources produce further challenges in setting the research agenda and for ensuring equity in the dissemination of research findings. Gender further complicates the aspiration for equity; the proportion of women in high administrative or research positions remains low. This study explores four specific mentoring case scenarios commonly encountered in the global health research field in low- and middle-income institutions.
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Global Health Mentoring Toolkits: A Scoping Review Relevant for Low- and Middle-Income Country Institutions
Available online: 14 November 2018More LessCapacity building in low- and middle-income country (LMIC) institutions hinges on the delivery of effective mentorship. This study presents an overview of mentorship toolkits applicable to LMIC institutions identified through a scoping review. A scoping review approach was used to 1) map the extent, range, and nature of mentorship resources and tools available and 2) to identify knowledge gaps in the current literature. To identify toolkits, we collected and analyzed data provided online that met the following criteria: written in English and from organizations and individuals involved in global health mentoring. We searched electronic databases, including PubMed, Web of Science, and Google Scholar, and Google search engine. Once toolkits were identified, we extracted the available tools and mapped them to pre-identified global health competencies. Only three of the 18 identified toolkits were developed specifically for the LMIC context. Most toolkits focused on individual mentor–mentee relationships. Most focused on the domains of communication and professional development. Fewer toolkits focused on ethics, overcoming resource limitations, and fostering institutional change. No toolkits discussed strategies for group mentoring or how to adapt existing tools to a local context. There is a paucity of mentoring resources specifically designed for LMIC settings. We identified several toolkits that focus on aspects of individual mentor–mentee relationships that could be adapted to local contexts. Future work should focus on adaptation and the development of tools to support institutional change and capacity building for mentoring.
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Mentorship Training is Essential to Advancing Global Health Research
Available online: 14 November 2018More LessMentorship Training is Essential to Advancing Global Health Research
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Integrating Case Detection of Visceral Leishmaniasis and Other Febrile Illness with Vector Control in the Post-Elimination Phase in Nepal
Available online: 12 November 2018More LessNepal has completed the attack phase of visceral leishmaniasis (VL) elimination and now needs active case detection (ACD) and vector control methods that are suitable to the consolidation and maintenance phases. We evaluated different ACD approaches and vector control methods in Saptari district. We assessed 1) mobile teams deployed in villages with VL cases in 2015 to conduct combined camps for fever and skin lesions to detect VL/PKDL (post–kala-azar dermal leishmaniasis) and other infections; 2) an incentive approach by trained female community health volunteers (FCHVs) in villages with no VL cases in 2015. Both were followed by house-to-house visits. For vector control, four villages were randomly allocated to insecticide impregnation of bednets, insecticide wall painting, indoor residual spraying (IRS), and control. Sandfly density (by CDC light traps) and mortality (World Health Organization cone bioassay) were assessed in randomly selected households. One VL, three tuberculosis, one leprosy, and one malaria cases were identified among 395 febrile cases attending the camps. Post-camp house-to-house screening involving 7,211 households identified 679 chronic fever and 461 skin lesion cases but no additional VL/PKDL. No VL/PKDL case was found by FCHVs. The point prevalence of chronic fever in camp and FCHV villages was 242 and 2 per 10,000 populations, respectively. Indoor residual spraying and bednet impregnation were effective for 1 month versus 12 months with insecticidal wall paint. Twelve-month sandfly mortality was 23%, 26%, and 80%, respectively, on IRS, bednet impregnation, and insecticide wall painting. In Nepal, fever camps and insecticidal wall paint prove to be alternative, sustainable strategies in the VL post-elimination program.
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Zika Virus in Israeli Travelers: Emergence of Asia as a Major Source of Infection
Available online: 12 November 2018More LessZika virus (ZIKV) had emerged as a global arboviral concern since late 2015. In this study, we describe the results of ZIKV testing in returning Israeli travelers from Zika-endemic countries. We conducted a nation-wide prospective observational study, including all ZIKV tests during January 2016–June 2017. Zika virus infection was defined as confirmed, if diagnosed by PCR or serology confirmed by neutralization, and as possible if diagnosed by serology alone. During the study period, 1,188 travelers were tested: 66.7%, 30.5%, 1.6%, and 1.2% had returned from the Americas, Asia, Africa, and Oceania, respectively. Thirty persons were diagnosed with ZIKV. Most travelers tested were women of reproductive age; the gender ratio among infected travelers however was 1.0. During 2016, 19/20 (95%) ZIKV cases were acquired in the Americas; in 2017, however, 6/10 (60%) cases were acquired in Asia. Of 248 symptomatic travelers, 28 (11.3%) were diagnosed with ZIKV infection, whereas only 2/940 (0.2%) of asymptomatic travelers were diagnosed with ZIKV infection Odds ratio = 59.7 (95% confidence interval: 14.1–252.5, P < 0.0001). Our findings suggest that although women are more likely to be referred for ZIKV testing, gender does not affect the likelihood of ZIKV infection and that asymptomatic ZIKV infection appears to be rare in travelers. Furthermore, it appears that in 2017, Southeast Asia emerges as the leading source of travel-related ZIKV infection.
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Triatoma costalimai Naturally Infected by Trypanosoma cruzi: A Public Health Concern
Available online: 12 November 2018More LessThe rupestrian Triatoma costalimai species has been found infected by Trypanosoma cruzi in wild, peridomicile, and intradomicile environments in the municipality of Aurora do Tocantins, Tocantins, Brazil. Proximity between rock outcrops increases the risk of vector transmission of Chagas disease via this species. This work describes a focus of colonization by T. costalimai specimens infected by T. cruzi in rock outcrops located in an urban area in this municipality. Parasitological examination of feces from the collected specimens, axenic cultivation of T. cruzi–positive samples, and genetic characterization of the isolates were performed. Nymph and adult specimens were collected with a high infection prevalence (64.5%) for T. cruzi TCI. Participation of the T. costalimai species in the wild cycle of T. cruzi in rock outcrops located in an urban area demonstrates the need for entomological surveillance and control of vector transmission of Chagas disease in the municipality of Aurora do Tocantins, Tocantins.
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Evaluating PCR-Based Detection of Salmonella Typhi and Paratyphi A in the Environment as an Enteric Fever Surveillance Tool
Available online: 12 November 2018More LessWith prequalification of a typhoid conjugate vaccine by the World Health Organization, countries are deciding whether and at what geographic scale to provide the vaccine. Optimal local data to clarify typhoid risk are expensive and often unavailable. To determine whether quantitative real-time PCR can be used as a tool to detect typhoidal Salmonella DNA in the environment and approximate the burden of enteric fever, we tested water samples from urban Dhaka, where enteric fever burden is high, and rural Mirzapur, where enteric fever burden is low and sporadic. Sixty-six percent (38/59) of the water sources of Dhaka were contaminated with typhoidal Salmonella DNA, in contrast to none of 33 samples of Mirzapur. If these results can be replicated in larger scale in Bangladesh and other enteric fever endemic areas, drinking water testing could become a low-cost approach to determine the presence of typhoidal Salmonella in the environment that can, in turn, guide informed-design of blood culture-based surveillance and thus assist policy decisions on investing to control typhoid.
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Case Report: Percutaneous Treatment of Multiple Echinococcal Cysts Presenting as Abdominal Palpable Mass
Available online: 12 November 2018More LessWe report the case of an adolescent Moroccan girl with abdominal pain and palpable mass in the upper right side of the abdomen. In the emergency department, an abdominal ultrasound showed hepatomegaly and eight active liver cysts, compatible with cystic echinococcosis. Serology for Echinococcus granulosus confirmed the diagnosis. Other sites of localization were excluded. Treatment involved albendazole combined with puncture, aspiration, injection, re-aspiration, performed only for the most medial cysts. Periodical follow-up with abdominal ultrasound and with abdominal magnetic resonance imaging showed a progressive involution of all cysts. The treatment with albendazole was stopped after, overall, 6 months, and monthly ultrasound scan were planned as follow-up. In case of hepatic cysts, E. granulosus should be excluded, especially in children from endemic countries. A multidisciplinary approach with pediatric infectious disease specialists, radiologists, and surgeons is fundamental for disease management.
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Artemisinin Resistance Outside of Southeast Asia
Available online: 12 November 2018More LessArtemisinin Resistance Outside of Southeast Asia
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Factors Associated with Dengue Virus Infection and Reinfection in Asymptomatic Children in Two Colombian Municipalities
Available online: 05 November 2018More LessDengue is the most important arbovirosis in the world. In this study, we assessed the knowledge, attitudes, and practices (KAP) regarding dengue in parents from two small Colombian municipalities in the Cundinamarca Province. Parents and their healthy children from 4 to 14 years of age were included in some public elementary schools. After a medical examination, blood samples were taken for diagnosis of dengue using enzyme-linked immunosorbent assays (capture IgM and IgG, and indirect IgG and NS1) and detection of viral RNA by reverse transcription polymerase chain reaction. In addition, a KAP survey was applied to the children’s parents or tutors. The indirect IgG test determined that of the 347 examined children, 87.9% had a previous infection with the dengue virus (DENV), 12.7% of them were positive for viral RNA (asymptomatic infection), and 32.0% presented reinfections. Risk factors evaluation showed that children aged 8 years and older living in the municipalities for more than 7 years were more likely to be infected or reinfected by DENV. In the same way, poor nutrition, lack of water supply, sewer service, or waste disposal services could raise the likelihood of dengue infections. The surveys indicated that parents have unhealthy practices and a low knowledge about the transmission of the disease, which could result in an increase of mosquito breeding sites, allowing sustained dengue transmission.
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Growth Status, Inflammation, and Enteropathy in Young Children in Northern Tanzania
Available online: 05 November 2018More LessRecent evidence suggests that enteropathy of the gut due to environmental conditions (i.e., environmental enteropathy [EE]) in young children is negatively associated with linear growth. Using a case–control study design, we examined the potential determinants of stunting in stunted and non-stunted children 22–28 months of age. Potential determinants included inflammation biomarkers C-reactive protein, alpha-1-acid glycoprotein (AGP), and endotoxin-core antibody (EndoCAb) measured in serum samples; enteropathy markers alpha-1-antitrypsin, neopterin, myeloperoxidase (MPO) measured in stools samples; and demographic, health, feeding, and household characteristics. We also explored the determinants of EE by testing associations of composite EE scores and individual biomarkers with potential risk factors. Fifty-two percent of children (n = 310) were found to be stunted, and mean height-for-age Z scores (HAZ) were −1.22 (SD ± 0.56) among non-stunted (control) children and −2.82 (SD ± 0.61) among stunted (case) children. Child HAZ was significantly (P < 0.05) and inversely associated with AGP, and child stunting was significantly associated (P < 0.05) with low dietary diversity, severe household hunger, and absence of soap in the household. Alpha-1-acid glycoprotein and EndoCAb concentrations were also significantly higher (P < 0.05) among children in households with no soap. Our study documented a seemingly localized cultural practice of young children (25%) being fed their dirty bathwater, which was associated with significantly higher concentrations of MPO (P < 0.05). Alpha-1-acid glycoprotein showed the most consistent associations with child growth and hygiene practices, but fecal EE biomarkers were not associated with child growth. The lack of retrospective data in our study may explain the null findings related to fecal EE biomarkers and child growth.
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Zika Virus and the Safety of Blood Supply in Brazil: A Retrospective Epidemiological Evaluation
Available online: 05 November 2018More LessThe potential for transfusion transmission of dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) has raised concerns about the safety of the blood supply in endemic areas. In this study, nucleic acid testing (NAT) for ZIKV, DENV, and CHIKV RNA was performed in asymptomatic blood donor samples in the city of Campinas, located in the southeast region of Brazil (1962 in 2015 and 1775 in 2016). The prevalence of reactive NAT was 0.15% in 2015 and 0.62% in 2016 for dengue, 0.05% in 2015 and 0.17% in 2016 for Zika, and 0% in both years for chikungunya. These results demonstrate the weakness of the clinical interview in screening these blood donors. Furthermore, positivity for ZIKV was detected in March 2015, 1 year before the first reported cases in the region. These data attest the feasibility of using donor samples held in library as a tool for retrospective epidemiological evaluation, which is particularly interesting considering emerging pathogens, for which data on their spread and penetrance are initially scarce.
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Use of Real-Time Polymerase Chain Reaction to Differentiate between Pathogenic Entamoeba histolytica and the Nonpathogenic Entamoeba dispar in Ecuador
Available online: 05 November 2018More LessMicroscopic examination of stool samples has been considered to be the “gold standard” for diagnosis of intestinal parasites. Recently, polymerase chain reaction (PCR) has been approved by the World Health Organization as the method of choice for the diagnosis of Entamoeba histolytica. Of the 106 stool samples collected from the Esmeraldas and Pichincha provinces of Ecuador, all (100%) were positive for E. histolytica/Entamoeba dispar by light microscopy, whereas using real-time PCR (RT-PCR) DNA amplification, 74 (69.8%) were positive for E. dispar and only three (2.8%) were positive for E. histolytica. Some 29 (27.4%) samples were negative for the presence of either E. histolytica or E. dispar, this may be due the presence of Entamoeba mosksvskii, which is morphologically identical to E. histolytica/E. dispar and not specifically targeted by the RT-PCR used. These results indicate the necessity of reevaluating the epidemiology of amebiasis in Ecuador as the prominent species found are nonpathogenic.
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Acute Post-Streptococcal Glomerulonephritis in the Northern Territory of Australia: A Review of Data from 2009 to 2016 and Comparison with the Literature
Available online: 05 November 2018More LessAcute post-streptococcal glomerulonephritis (APSGN) is an inflammatory kidney disease following infection with nephritogenic strains of group A Streptococcus. In 1991, APSGN became notifiable in the Northern Territory (NT) of Australia with cases recorded on the NT Notifiable Disease Database (NTNDS). The case definition of a confirmed case requires laboratory definitive evidence or laboratory suggestive evidence in conjunction with a clinically compatible illness. Probable cases require clinical evidence only. Acute post-streptococcal glomerulonephritis notifications from 2009 to 2016 were extracted from the NTNDS. Of the 322 cases, 261 were confirmed and 61 probable. The majority, 304 (94%), were Aboriginal and the median age was 8 years (range: 0–62 years). Incidence for confirmed cases was 13.8/100,000 person-years, with inclusion of probable cases increasing incidence to 17.0/100,000 person-years. Highest incidence of confirmed cases was in Aboriginal children less than 15 years of age at 124.0 cases/100,000 person-years. The rate ratio of confirmed cases in Aboriginal to non-Aboriginal Australians was 18.9 (95% confidence interval: 11.4–33.6). Recent trends show a consistently high number of notifications annually with less frequent outbreaks. The Aboriginal population of the NT continues to have high rates of APSGN with recent trends showing higher rates than previously reported. Sustained preventative efforts and continued surveillance strategies are needed.
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Dengue Virus Infection of Primary Human Smooth Muscle Cells
Available online: 05 November 2018More LessDengue virus (DENV) infection of humans is presently the most important arthropod-borne viral global threat, for which no suitable or reliable animal model exists. Reports addressing the effect of DENV on vascular components other than endothelial cells are lacking. Dengue virus infection of vascular smooth muscle cells, which play a physiological compensatory response to hypotension in arteries and arterioles, has not been characterized, thus precluding our understanding of the role of these vascular components in dengue pathogenesis. Therefore, we studied the permissiveness of primary human umbilical artery smooth muscle cells (HUASMCs) to DENV 1–4 infection and compared with the infection in the previously reported primary human umbilical vein endothelial cells (HUVECs) and the classically used, non-transformed, and highly permissive LLC-MK2 cells (macaque kidney cells). Our results show that HUASMC are susceptible and productive to infection with the four DENV serotypes, although to a lesser extent when compared with the other cell lines. This is the first report of DENV permissiveness in human smooth muscle cells, which might represent an unexplored pathophysiological contributor to the vascular collapse observed in severe human dengue infection.
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Depressive Symptoms Mediate the Associations of Stigma with Medication Adherence and Quality of Life in Tuberculosis Patients in China
Available online: 05 November 2018More LessStigma has been associated with health-related outcomes such as medication adherence and quality of life (QOL) in patients with tuberculosis (TB); however, the mechanisms via which TB-related stigma interferes with specific outcomes are unclear. This study aimed to determine whether depressive symptoms were one of the mechanisms that mediated the associations between TB-related stigma and both medication adherence and QOL in patients with TB. A cross-sectional survey was conducted between October 1, 2013, and March 31, 2014, in Hubei Province, central China, and data were collected from 1,342 patients with TB, using a structured questionnaire that measured TB-related stigma, depressive symptoms, medication adherence, and QOL. Multiple imputation was used to account for missing data. Structural equation modeling was performed to assess the mediating effect of depressive symptoms on the associations of TB-related stigma with medication adherence and QOL. Mediation analyses showed that depressive symptoms partially mediated the association between TB-related stigma and medication adherence (standardized indirect effect = −0.16, 95% bias-corrected confidence interval [CI] [−0.19, −0.13], P < 0.01). Moreover, depressive symptoms fully mediated the association between TB-related stigma and QOL (standardized indirect effect = −0.17, 95% bias-corrected CI [−0.21, −0.14], P < 0.01). The results suggest that depressive symptoms played a key role in the relationships among TB-related stigma, medication adherence, and QOL in patients with TB. Therefore, the alleviation of depressive symptoms could be an important strategy for improving medication adherence and QOL in patients with TB.
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Handheld Point-of-Care Lactate Measurement at Admission Predicts Mortality in Ugandan Children Hospitalized with Pneumonia: A Prospective Cohort Study
Available online: 05 November 2018More LessGlobally, pneumonia is the leading cause of death among children younger than 5 years old, with most deaths occurring in low-income countries. Rapid bedside tools to assist practitioners to accurately triage and risk-stratify these patients may improve clinical care and patient outcomes. We conducted a prospective cohort study of children with pneumonia admitted to two Ugandan hospitals to examine the predictive value of a single point-of-care lactate measurement using a commercially available handheld device, the Lactate Scout Analyzer. One hundred and fifty-five children were included, 90 (58%) male, with a median (interquartile range [IQR]) age of 11 (1.4–20) months. One hundred and twenty-five (81%) patients had chest indrawing, 133 (86%) were hypoxemic, and 75 (68%) had a CXR abnormality. In-hospital mortality was 22/155 (14%). Median (IQR) admission lactate level was 2.4 (1.8–3.6) mmol/L among children who survived versus 7.2 (2.6–9.7) mmol/L among those who died (P < 0.001). Lactate was a better prognostic marker of mortality (area under receiver operator characteristic 0.76, 95% CI: 0.69–0.87, P ≤ 0.001), than any single clinical sign or composite clinical risk score. Lactate level at admission of < 2.0, 2.0–4.0, and > 4.0 mmol/L accurately risk-stratified children, with 5-day mortality of 2%, 11% and 26%, respectively (P < 0.001). Slow lactate clearance also predicted subsequent mortality in children with repeated lactate measurements. Hand-held lactate measurement is a clinically informative and convenient tool in low-resource settings for triage and risk stratification of pediatric pneumonia.
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Whatman Protein Saver Cards for Storage and Detection of Parasitic Enteropathogens
Available online: 05 November 2018More LessCurrent methods to identify the etiology of diarrhea require laboratory facilities for storage of pathogens, which is often challenging in low-resource settings. This study evaluated the efficacy of a low-cost method for preserving stool specimens for the detection of parasitic enteropathogens using Whatman 903 protein saver cards (Sigma-Aldrich). Stool samples known to be positive by multiplex real-time PCR for Giardia lamblia, Cryptosporidium spp., and Entamoeba histolytica parasites were preserved on 232 Whatman cards. DNA was then extracted from cards using Chelex and Qiagen extraction protocols, and tested for these parasites using multiplex real-time PCR. We included stool samples known to have a higher parasite load (cycle threshold [ct]-value < 30) and those with a lower parasite load (ct values 30–35). Sensitivities and specificities were determined using DNA extracted directly from whole stool samples using Qiagen kits. For whole stool samples with ct values < 30, preserved directly on Whatman 903 protein saver cards for Giardia analysis, the sensitivity was 100% for both Qiagen and Chelex DNA extraction. For E. histolytica, this was 100% for sensitivity for Qiagen and 80% for Chelex DNA extractions, and for Cryptosporidium, this was 80% for Qiagen and 50% for Chelex DNA extraction. The specificity was 100% for all parasites for all extraction procedures. Given the high sensitivity for stool samples with higher parasite loads, we recommend the use of the Whatman 903 protein saver card for preserving fecal specimens for the analysis of Giardia and E. histolytica using Qiagen DNA extractions in low-resource settings.
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Molecular Evidence for Plasmodium falciparum Resistance to Sulfadoxine–Pyrimethamine but Absence of K13 Mutations in Mangaluru, Southwestern India
Available online: 05 November 2018More LessIn most of India, sulfadoxine–pyrimethamine (SP) plus artesunate serves as first-line treatment for uncomplicated falciparum malaria. In 112 clinical Plasmodium falciparum isolates from Mangaluru, southwestern India, we sequenced molecular markers associated with resistance to SP, lumefantrine, and artemisinin (pfdhfr, pfdhps, pfmdr1, and K13). The pfdhfr double mutation 59R-108N combined with the dhps 437G mutation occurred in 39.3% and the pfdhfr double mutation plus the pfdhps double mutation 437G-540E in additional 24.1%. As for pfmdr1, the allele combination N86-184F-D1246 dominated (98.2%). K13 variants were absent.
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Accuracy of Urine and Serum Assays for the Diagnosis of Strongyloidiasis by Three Enzyme-Linked Immunosorbent Assay Protocols
Available online: 05 November 2018More LessTo evaluate the accuracy and reliability of urine assay for the diagnosis of strongyloidiasis, three different immunoassays were used to assess the diagnostic accuracy of anti-Strongyloides IgG in urine and compared with those in serum samples. Analyses by InBios enzyme-linked immunosorbent assay (ELISA) kit (NIE recombinant antigen), SciMedx ELISA kit (Strongyloides stercoralis antigen), and our in-house ELISA (S. ratti antigen) yielded comparable diagnostic performances between urine and serum assays. Levels of Strongyloides-specific IgG in urine significantly correlated with those in serum. Tests for diagnostic agreement between urine and serum IgG assays showed substantial to moderate agreement (κ = 0.207–0.615). The observed quantitative and qualitative concordance between urine and serum assays in strongyloidiasis suggests that urine has similar diagnostic value to that for serum. Because of the ease and noninvasiveness of clinical sample collection, urine assay has a high potential for the initial diagnosis and mass screening of strongyloidiasis.
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Case Reports: Prolonged Detection of Zika Virus RNA in Vaginal and Endocervical Samples from a Brazilian Woman, 2018
Available online: 05 November 2018More LessZika virus (ZIKV) infection is an emerging public health problem, associated with increased risk for Guillain–Barré syndrome and adverse fetal outcomes, including congenital microcephaly. Zika virus sexual transmission is known, but detection of the virus in different parts of the female reproductive tract is not well established. In this case report, we describe prolonged detection of ZIKV RNA in the vaginal secretion and endocervical mucosa from a Brazilian woman convalescent to ZIKV infection. A viral load of 2 × 102 copies/mL was detected up to 31 days after symptom onset in both samples. Other biological fluids, including whole blood, plasma, serum, urine, and saliva samples, were negative for ZIKV RNA. These findings advance the understanding of ZIKV infection and provide data for additional testing strategies.
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Case Report: Survival from Rabies: Case Series from India
Available online: 05 November 2018More LessRabies, a zoonotic viral encephalitis, continues to be a serious public health problem in India and several other countries in Asia and Africa. Survival is rarely reported in rabies, which is considered to be almost universally fatal. We report the clinical and radiological findings of eight patients with laboratory-confirmed rabies who survived the illness. With the exception of one patient who recovered with mild sequelae, all survivors had poor functional outcomes. The reported survival from rabies in recent years may reflect an increased awareness of the disease and greater access to better critical care facilities in rabies-endemic countries. Nonetheless, there is an urgent need to focus on preventive strategies to reduce the burden of this dreadful disease in rabies-endemic countries.
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Molecular Diagnosis of Microsporidia among Immunocompromised Patients in Kuala Lumpur, Malaysia
Available online: 29 October 2018More LessMicrosporidia are obligate intracellular parasitic fungi causing chronic diarrhea, particularly among immunocompromised patients. The current method used for diagnosis is based on conventional microscopy, which does not differentiate parasites at the species level. The present study was carried out to identify microsporidian species in immunocompromised patients. From March 2016 to March 2017, a total of 289 archived stool samples were examined microscopically for microsporidian spores using Gram-chromotrope Kinyoun (GCK) stain. Positive stool samples by microscopy were subjected to polymerase chain reaction and sequencing for species identification. Based on microscopy examination, the overall prevalence of microsporidian infections was 32.2% (93/289; 95% CI = 27.1–37.8). Of these stool samples, 45 samples were successfully amplified and confirmed as Enterocytozoon bieneusi. No Encephalitozoon intestinalis was detected. Accurate identification of species might help clinicians to decide appropriate management strategies as dissemination risks and treatment response vary for different species, hence improving the management of microsporidian infections.
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Housing Characteristics and Leishmaniasis: A Systematic Review
Available online: 29 October 2018More LessLeishmaniasis is a major neglected tropical disease associated with high rates of disability and death. This disease is associated with poverty, which can be reflected in housing quality, especially in rural areas. This systematic review found that mud walls with cracks and holes, damp, and dark houses were risk factors for transmission of leishmaniasis. These characteristics create favorable conditions for sand fly breeding and resting as sand flies prefer humidity, warmth, and protection from sunlight during the day. Housing interventions might be a promising research area with a special focus on education as individual and collective protection for the effective control of leishmaniasis.
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Mycobacterium tuberculosis Drug Resistance and Transmission among Human Immunodeficiency Virus–Infected Patients in Ho Chi Minh City, Vietnam
Available online: 29 October 2018More LessVietnam has a high burden of tuberculosis (TB) and multidrug-resistant (MDR) TB, but drug resistance patterns and TB transmission dynamics among TB/human immunodeficiency virus (HIV) coinfected patients are not well described. We characterized 200 Mycobacterium tuberculosis isolates from TB/HIV coinfected patients diagnosed at the main TB referral hospital in Ho Chi Minh City, Vietnam. Phenotypic drug susceptibility testing (DST) for first-line drugs, spoligotyping, and 24-locus mycobacterial interspersed repetitive unit (MIRU-24) analysis was performed on all isolates. The 24-locus mycobacterial interspersed repetitive unit clusters and MDR isolates were subjected to whole genome sequencing (WGS). Most of the TB/HIV coinfected patients were young (162/174; 93.1% aged < 45 years) males (173; 86.5% male). Beijing (98; 49.0%) and Indo-Oceanic (70; 35.0%) lineage strains were most common. Phenotypic drug resistance was detected in 84 (42.0%) isolates, of which 17 (8.5%) were MDR; three additional MDR strains were identified on WGS. Strain clustering was reduced from 84.0% with spoligotyping to 20.0% with MIRU-24 typing and to 13.5% with WGS. Whole genome sequencing identified five additional clusters, or members of clusters, not recognized by MIRU-24. In total, 13 small (two to three member) WGS clusters were identified, with less clustering among drug susceptible (2/27; 7.4%) than among drug-resistant strains (25/27; 92.6%). On phylogenetic analysis, strains from TB/HIV coinfected patients were interspersed among strains from the general community; no major clusters indicating transmission among people living with HIV were detected. Tuberculosis/HIV coinfection in Vietnam was associated with high rates of drug resistance and limited genomic evidence of ongoing M. tuberculosis transmission among HIV-infected patients.
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Virus Reduction Neutralization Test: A Single-Cell Imaging High-Throughput Virus Neutralization Assay for Dengue
Available online: 22 October 2018More LessVaccine immunogenicity and clinical efficacy are often assessed by the measure of serum-neutralizing antibodies. The present gold standard for detecting neutralizing antibodies against many viruses, including dengue, is the plaque/focus reduction neutralization test (P/FRNT). The FRNT is a cell-based assay that inherits high variability, resulting in poor precision and has lengthy turnaround times. The virus reduction neutralization test (VRNT) is a high-throughput alternative to the standard low-throughput and laborious FRNT. The VRNT is similar to FRNT using unaltered wild-type virus and immunostaining, yet uses imaging cytometry to count virus-infected cells 1 day post-infection, reducing assay time and increasing overall throughput 15-fold. In addition, the VRNT has lowered variability relative to FRNT, which may be explained in part by the observation that foci overlap alters foci count and titer over time, in the FRNT. The ability to count one infected cell, rather than waiting for overlapping foci to form, ensures accuracy and contributes to the precision (7–25% coefficient of variation) and sensitivity of the VRNT. Results from 81 clinical samples tested in the VRNT and FRNT show a clear positive relationship. During sample testing, a 96-well plate edge effect was noted and the elimination of this edge effect was achieved by a simple plate seeding technique. The VRNT is an improvement to the current neutralization assays for its shortened assay time, increased precision and throughput, and an alternative to the P/FRNT.
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Prevalence of Caries among Schoolchildren in the Interior of Suriname
Available online: 22 October 2018More LessThe aim of this study was to determine the prevalence of caries among children living in the interior of Suriname and to investigate the influence of the reachability of their habitats and different ethnicities on the prevalence of caries. As part of children’s regular dental check-ups, data on the prevalence of caries were registered for schoolchildren (n = 1,309) living in four different regions. Prevalence of caries was expressed by the number of decayed, missing, and filled teeth (DMFT index). Consequences of severe caries were recorded by counting the number of teeth with pulp involvement, ulcerations, fistulas, and abscesses. Depending on the habitat, the number of children with caries in their primary dentition varied between 68% and 100%, in the mixed dentition between 79% and 98%, and in their permanent dentition between 54% and 94%. After the World Health Organization criteria, the average scores of dmft were high in children with primary teeth (except for Brokopondo), moderate to high in children with mixed dentition and low to moderate in children with permanent teeth. Children in more remote areas had a greater prevalence of caries than children in less remote regions. Severe consequences of caries were seen in 14–75% of the children. Treatments were rarely performed. Children in the interior of Suriname are in great need of preventive and curative dental treatments.
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The Effect of School Closure on Hand, Foot, and Mouth Disease Transmission in Singapore: A Modeling Approach
Available online: 22 October 2018More LessSingapore implements school closure policy for institutional hand, foot, and mouth disease (HFMD) outbreaks, but there is a lack of empirical evidence on the effect of closure on HFMD transmission. We conducted a retrospective analysis of 197,207 cases of HFMD over the period 2003–2012 at the national level and of 57,502 cases in 10,080 institutional outbreaks over the period 2011–2016 in Singapore. The effects of school closure due to 1) institutional outbreaks, 2) public holidays, and 3) school vacations were assessed using a Bayesian time series modeling approach. School closure was associated with a reduction in HFMD transmission rate. During public holidays, average numbers of secondary cases having onset the week after dropped by 53% (95% credible interval 44–62%), and during school vacations, the number of secondary cases dropped by 7% (95% credible interval 3–10%). Schools being temporarily closed in response to an institutional outbreak reduced the average number of new cases to 1,204 (95% credible interval 1,140–1,297). Despite the positive effect in reducing transmission, the effect of school closure is relatively small and may not justify the routine use of this measure.
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Unsafe Drinking Water Is Associated with Environmental Enteric Dysfunction and Poor Growth Outcomes in Young Children in Rural Southwestern Uganda
Available online: 22 October 2018More LessEnvironmental enteric dysfunction (EED), a subclinical disorder of the small intestine, and poor growth are associated with living in poor water, sanitation, and hygiene (WASH) conditions, but specific risk factors remain unclear. Nested within a birth cohort study, this study investigates relationships among water quality, EED, and growth in 385 children living in southwestern Uganda. Water quality was assessed using a portable water quality test when children were 6 months, and safe water was defined as lacking Escherichia coli contamination. Environmental enteric dysfunction was assessed using the lactulose:mannitol (L:M) test at 12–16 months. Anthropometry and covariate data were extracted from the cohort study, and associations were assessed using linear and logistic regression models. Less than half of the households (43.8%) had safe water, and safe versus unsafe water did not correlate with improved versus unimproved water source. In adjusted linear regression models, children from households with safe water had significantly lower log-transformed (ln) L:M ratios (β: −0.22, 95% CI: −0.44, −0.00) and significantly higher length-for-age (β: 0.29, 95% CI: 0.00, 0.58) and weight-for-age (β: 0.20, 95% CI: 0.05, 0.34) Z-scores at 12–16 months. Furthermore, in adjusted linear regression models, ln L:M ratios at 12–16 months significantly decreased with increasing length-for-age Z-scores at birth, 6 months, and 9 months (β: −0.05, 95% CI: −0.10, −0.004; β: −0.06, 95% CI: −0.11, −0.006; and β: −0.05, 95% CI: −0.09, −0.005, respectively). Overall, our data suggest that programs seeking to improve nutrition should address poor WASH conditions simultaneously, particularly related to household drinking water quality.
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16S Metagenomic Comparison of Plasmodium falciparum–Infected and Noninfected Anopheles gambiae and Anopheles funestus Microbiota from Senegal
Available online: 22 October 2018More LessIn the context of the pre-elimination of malaria, biological control may provide an alternative or additional tool to current malaria control strategies. During their various stages of development, mosquitoes undergo subsequent changes in their associated microbiota, depending on their environment and nutritional status. Although Anopheles gambiae s.l. and Anopheles funestus are the two major malaria vectors in Senegal, the composition of their microbiota is not yet well known. In this study, we explored the microbiota of mosquitoes naturally infected or not by Plasmodium falciparum (Pf) using the 16S ribosomal RNA gene-based bacterial metagenomic approach. In both vector species, the microbiota was more diverse in Pf-infected samples than in the noninfected ones, although the total number of reads appeared to be higher in noninfected mosquitoes. Overall, the microbiota was different between the two vector species. Noteworthy, the bacterial microbiota was significantly different between Pf-positive and Pf-negative groups whatever the species, but was similar between individuals of the same infection status within a species. Overall, the phylum of Proteobacteria was the most predominant in both species, with bacteria of the genus Burkholderia outweighing the others in noninfected vectors. The presence of some specific bacterial species such as Asaia bogorensis, Enterobacter cloacae, Burkholderia fungorum, and Burkholderia cepacia was also observed in Pf-free samples only. These preliminary observations pave the way for further characterization of the mosquito microbiota to select promising bacterial candidates for potential use in an innovative approach to controlling malaria and overcoming the challenges to achieving a malaria-free world.
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Molecular Surveillance of Plasmodium falciparum Drug Resistance Markers in Clinical Samples from Botswana
Available online: 22 October 2018More LessDrug-resistant Plasmodium falciparum is a major threat to global malaria control and elimination efforts. In Botswana, a southern African country approaching malaria elimination, P. falciparum molecular data are not available. Parasites were assessed through PCR for confirmation of positive rapid diagnostic tests, multiplicity of infection (MOI), and drug resistance markers among isolates from clinical uncomplicated malaria cases collected at health facilities. Of 211 dried blood spot samples selected for the study, 186 (88.2%) were PCR positive for P. falciparum. The mean MOI based on MSP1 genotyping was 2.3 and was not associated with age. A high prevalence of wild-type parasites for pfcrt and pfmdr1 was found, with a haplotype frequency (K76/N86) of 88.8% and 17.7% of the isolates having two copies of the pfmdr1 gene. For pfATPase6, all the parasites carried the wild-type S769 allele. Sequencing showed no evidence of non-synonymous mutations associated with reduced artemisinin derivative sensitivity in the P. falciparum k13 gene. In conclusion, we found that P. falciparum parasites in Botswana were mostly wild type for the drug resistance markers evaluated. Yet, there was a high rate of a molecular marker associated to reduced sensitivity to lumefantrine. Our results indicate the need for systematic drug efficacy surveillance to complement malaria elimination efforts.
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Chagas Disease in Southern Coastal Ecuador: Coinfections with Arboviruses and a Comparison of Serological Assays for Chagas Disease Diagnosis
Available online: 22 October 2018More LessOccurrence of Chagas disease and arbovirus coinfections is unknown, despite the vast co-endemic areas throughout the Americas. This study examined the proportion of individuals positive for Trypanosoma cruzi and coinfections with dengue, chikungunya, and Zika viruses in Machala, Ecuador (January 2014–December 2015). Chagas seropositivity was evaluated with five commercially available assays. Dengue infections were identified by nonstructural protein 1 rapid test and ELISA, IgM ELISA, and reverse transcription PCR (RT-PCR); chikungunya and Zika infections were identified by RT-PCR. Of 658 individuals, six were positive for T. cruzi (0.91%), including one T. cruzi/dengue coinfection and one T. cruzi/chikungunya/dengue coinfection (0.1%). The clinical manifestations of coinfected individuals corresponded to severe dengue and dengue with warning signs, respectively. We observed discrepant results by using the Hemagen Chagas kit and the rapid test Chagas Detect Plus (false positives: 3.9% and 15.4%), highlighting the need to assess diagnostic assays in geographic regions with distinct taxonomic units of T. cruzi.
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Laboratory Evaluation of a Rapid IgG4 Antibody Test (BLF Rapid™) for Bancroftian Filariasis
Available online: 22 October 2018More LessAt the end phase of the Global Programme to Eliminate Lymphatic Filariasis, antibody testing may have a role in decision-making for bancroftian filariasis–endemic areas. This study evaluated the diagnostic performance of BLF Rapid™, a prototype immunochromatographic IgG4-based test using BmSXP recombinant protein, for detection of bancroftian filariasis. The test was evaluated using 258 serum samples, comprising 96 samples tested at Universiti Sains Malaysia (in-house) and 162 samples tested independently at three international laboratories in the USA and India, and two laboratories in Malaysia. The independent testing involved 99 samples from Wuchereria bancrofti microfilaria or antigen positive individuals and 63 samples from people who were healthy or had other infections. The in-house evaluation showed 100% diagnostic sensitivity and specificity. The independent evaluations showed a diagnostic sensitivity of 84–100% and 100% specificity (excluding non-lymphatic filarial infections). BLF Rapid has potential as a surveillance diagnostic tool to make “Transmission Assessment Survey”–stopping decisions and conduct post-elimination surveillance.
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Characteristics and Severity of Disease among 100 Cases of Imported Malaria Seen at a U.S. University Hospital, 2000–2017
Available online: 22 October 2018More LessMalaria acquired in endemic areas poses a substantial risk to travelers arriving in or returning to the United States. Timely diagnosis and recognition of severe illness are crucial; however, many U.S.-based clinicians lack familiarity with this disease. We conducted a retrospective review of 100 cases of malaria in adults seen at a single urban university hospital during 2000–2017. Descriptive and analytical statistics were calculated, including logistic regression modeling case severity. Most of the patients presented with Plasmodium falciparum (76%), most commonly after travel from sub-Saharan Africa (94%). Prior malaria experience was common (50%), but adherence to a prophylactic regimen was exceedingly rare (4%). Twenty-one patients had severe malaria, including 10 with cerebral malaria. Severity was predicted by high parasitemia, bandemia, hypoglycemia, and hypotension at the time of presentation. In 24 patients, the initial treatment regimen was changed, usually because of the appearance of clinical deterioration or drug toxicity. One patient required intravenous artesunate. All patients survived, although one suffered fetal loss. Among 30 patients initially evaluated at other institutions, 43% had been treated for an alternative diagnosis. The most common reasons for transfer of patients to our hospital were inadequate facilities and lack of expertise with malaria. There needs to be increased awareness among U.S.-based travelers and clinicians regarding malaria as a potentially lethal condition, emphasizing the use of appropriate prophylaxis. Our simple model of disease severity could serve frontline physicians when deciding which patients should be admitted to the intensive care unit or transferred for higher level care.
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Evaluation of a Novel Quantitative Test for Glucose-6-Phosphate Dehydrogenase Deficiency: Bringing Quantitative Testing for Glucose-6-Phosphate Dehydrogenase Deficiency Closer to the Patient
Available online: 22 October 2018More LessGlucose-6-phosphate dehydrogenase (G6PD) deficiency, a common genetic blood condition, can result in kernicterus at birth, and later in life as severe hemolysis on exposure to certain infections, foods, and drugs. The unavailability of point-of-care tests for G6PD deficiency is a barrier to routine curative treatment of Plasmodium vivax malaria with 8-aminoquinolines, such as primaquine. Two quantitative reference tests (Trinity Biotech, Bray, Ireland and Pointe Scientific, MI; Cat No. G7583) and the point-of-care STANDARD™ G6PD test (SD Biosensor, South Korea) were evaluated. The STANDARD G6PD test was evaluated at multiple temperatures, in anticoagulated venous and capillary samples, including 79 G6PD-deficient and 66 intermediate samples and across two laboratories, one in the United States and one in Thailand. The STANDARD test performed equivalently to a reference assay for its ability to diagnose G6PD deficiency (< 30% normal) with a sensitivity of 100% (0.95 confidence interval [CI]: 95.7–100) and specificity of 97% (0.95 CI: 94.5–98.5), and could reliably identify females with less than 70% normal G6PD activity with a sensitivity of 95.5% (0.95 CI: 89.7–98.5) and specificity of 97% (0.95 CI: 94.5–98.6). The STANDARD G6PD product represents an opportunity to diagnose G6PD deficiency equally for males and females in basic clinical laboratories in high- and low-resource settings. This quantitative point-of-care diagnostic test for G6PD deficiency can provide equal access to safe radical cure of P. vivax cases in high- and low-resource settings, for males and females and may support malaria elimination, in countries where P. vivax is endemic.
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Case Report: Acute Hepatitis E in a Pediatric Traveler Presenting with Features of Autoimmune Hepatitis: A Diagnostic and Therapeutic Challenge
Available online: 22 October 2018More LessHepatitis E virus (HEV) is globally the most common cause of acute viral hepatitis. In industrialized countries, HEV infection can be seen in travelers returning from hyperendemic countries or in individuals at risk for autochthonous infection due to zoonotic exposure. Hepatitis E virus infection is often unrecognized and at times misdiagnosed because of nonspecific findings that can overlap with other causes of hepatitis, including autoimmune hepatitis (AIH). Although most cases of acute HEV infection resolve spontaneously and do not require treatment, life-threatening acute liver failure may occur in some cases. We discuss the case of an 8-year-old boy returning from Bangladesh with progressive acute liver injury and a clinical profile suggestive of AIH, who showed a favorable response to corticosteroid treatment before the diagnosis of an acute HEV infection could be established.
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Strength in Numbers: The WWARN Case Study of Purpose-Driven Data Sharing
Available online: 22 October 2018More LessData are the basis for all scientific output. The sharing of data supporting that output is an important aspect of scientific communication, and is increasingly required by funders and publishers. Yet, academic advancement seldom recognizes or rewards data sharing. This article argues that although mandating data sharing will increase the amount of data available, this will not necessarily enable or encourage the secondary analyses needed to achieve its purported public good. We, therefore, need to build models that maximize the efficiency of processes for data collation and curation, and genuinely reward those engaged in data sharing and reuse. The WorldWide Antimalarial Resistance Network has 10 years of experience as a data platform, and its study group approach provides an example of how some of the challenges in equitable and impactful data-sharing and secondary use can be addressed, with a focus on the priorities of researchers in resource-limited settings.
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New Prototype Screened Doors and Windows for Excluding Mosquitoes from Houses: A Pilot Study in Rural Gambia
Available online: 22 October 2018More LessDespite compelling evidence that modern housing protects against malaria, houses in endemic areas are still commonly porous to mosquitoes. The protective efficacy of four prototype screened doors and two windows designs against mosquito house entry, their impact on indoor climate, as well as their use, durability and acceptability was assessed in a Gambian village. A baseline survey collected data on all the houses and discrete household units, each consisting of a front and back room, were selected and randomly allocated to the study arms. Each prototype self-closing screened door and window was installed in six and 12 units, respectively, with six unaltered units serving as controls. All prototype doors reduced the number of house-entering mosquitoes by 59–77% in comparison with the control houses. The indoor climate of houses with screened doors was similar to control houses. Seventy-nine percentage of door openings at night occurred from dusk to midnight, when malaria vectors begin entering houses. Ten weeks after installation the doors and windows were in good condition, although 38% of doors did not fully self-close and latch (snap shut). The new doors and windows were popular with residents. The prototype door with perforated concertinaed screening was the best performing door because it reduced mosquito entry, remained fully functional, and was preferred by the villagers. Screened doors and windows may be useful tools for reducing vector exposure and keeping areas malaria-free after elimination, when investment in routine vector control becomes difficult to maintain.
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Comparison of the Impact of Different Mass Drug Administration Strategies on Infection with Schistosoma mansoni in Mwanza Region, Tanzania—A Cluster-Randomized Controlled Trial
Available online: 22 October 2018More LessAnnual school-based mass drug administration with praziquantel has been widely implemented to control schistosomiasis, but other treatment strategies could have a different impact. The aim of this study was to investigate the impact of six different treatment strategies on Schistosoma mansoni infection in a cluster-randomized controlled trial in schoolchildren, in a high transmission area of the Mwanza Region, Tanzania. A total of 150 villages were randomized into six arms with 25 villages in each arm. In each village, approximately 100 schoolchildren aged 9–12 years were randomly selected each year and investigated for S. mansoni prevalence and intensity based on three consecutive stool samples using the duplicate Kato–Katz technique. Four years of community-wide treatment (CWT) was the most intensive treatment strategy, whereas 2 years of school-based treatment (SBT) combined with 2 years without treatment (holiday) was the least intensive treatment. The remaining strategies constituted different combinations of CWT, SBT, and holiday years. Baseline results on S. mansoni infection were obtained from 14,620 schoolchildren from 148 villages, and mean prevalence and mean intensity among infected were 48.6–60.6% and 130.5–229.8 eggs per gram, respectively. Over the years, mean prevalence and mean intensities declined in all arms, but when comparing year 5 mean prevalence and mean intensity, there were no statistically significant differences between treatment arms. Thus, measured in a random selection of schoolchildren aged 9–12 years, four times CWT was not superior to four times SBT, while 2 years of treatment holiday combined with 2 years of SBT had the same impact as 4 years of SBT.
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Visceral Leishmaniasis in Hospitalized HIV-Infected Patients in Pernambuco, Brazil
Available online: 15 October 2018More LessCommon in four continents, visceral leishmaniasis (VL) is an important but neglected disease. HIV infection increases the risk of developing VL in people from leishmaniasis-endemic areas, with worse prognosis when there is coinfection. We conducted a cross-sectional study to determine the prevalence of HIV/VL coinfection in patients admitted in three referral hospitals for HIV/AIDS in Pernambuco, Brazil, and to compare epidemiological, clinical, and laboratory characteristics among HIV/VL coinfected and HIV mono-infected individuals. The sample consisted of HIV patients aged 18 years or more, in a period of data collection of 6 months. We performed four Leishmania tests—PCR, direct agglutination test, rK39, and latex agglutination test—and individuals with at least one positive test were considered coinfected. The HIV/VL coinfection prevalence we found was 16.9%. We observed large variation in prevalence according to the Leishmania test used, with low coincidence of positive tests. The most frequent symptoms found were weight loss (75.6%), fever (67.6%), and cough (55.3%). When we compared HIV/VL coinfected and HIV mono-infected groups we did not observe statistically significant differences. Low educational level (P = 0.004) and pallor (P = 0.009) were more frequent in the coinfected group. Serum albumin level was higher in coinfected individuals (P = 0.009). It is important to follow-up these individuals to understand the dynamics of VL in people living with HIV. New tests are necessary, ideally differentiating active from latent infection. Testing for VL in people with HIV is important and should be considered as part of the initial investigation in these individuals.
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Perinatal Outcomes in Vertically Infected Neonates During a Chikungunya Outbreak on the Island of Curaçao
Available online: 15 October 2018More LessRecent outbreaks of Chikungunya virus (CHIKV) infection confirm the vulnerability of neonates after vertical transmission. In 2014, CHIKV was reported for the first time in the Americas, including the island of Curaçao. We describe the outcomes of symptomatic neonates with vertically transmitted CHIKV infection during the CHIKV epidemic, who were admitted in the Saint Elisabeth Hospital, Willemstad, Curaçao. There were three symptomatic neonates with serologically confirmed infection. Two neonates developed neurological complications, including convulsions and intracerebral bleeding. One newborn, in whom maternal infection occurred 7 weeks before delivery, had a fatal outcome after birth. Maternal-fetal transmission of CHIKV may cause severe neonatal complications. There is a need to share experiences and to implement protocols toward the management of perinatal CHIKV infection.
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New Evidence of the Monophyletic Relationship of the Genus Psammolestes Bergroth, 1911 (Hemiptera, Reduviidae, and Triatominae)
Available online: 15 October 2018More LessThe genus Psammolestes within the subfamily Triatominae and tribe Rhodniini comprises the species Psammolestes arthuri, Psammolestes coreodes, and Psammolestes tertius, all potential vectors of Chagas disease. A feature of Psammolestes is their close association with birds, which makes them an interesting model for evolutionary studies. We analyzed cytogenetically Psammolestes spp., with the aim of contributing to the genetic and evolutionary knowledge of these vectors. All species of the Psammolestes showed the same chromosomal characteristics: chromocenter formed only by sex chromosomes X and Y, karyotype 2n = 22 and constitutive heterochromatin, and AT base pairs restricted to the sex chromosome Y. These results corroborate the monophyly of the genus and lead to the hypothesis that during the derivation of P. tertius, P. coreodes, and P. arthuri from their common ancestor, there was no reorganization in the number or structure of chromosomes.
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Hepatitis B Infection among Parturient in Peri-Urban Ghana
Available online: 08 October 2018More LessGlobal evidence suggests that hepatitis B viral (HBV) infection is endemic in Africa and perinatal transmission remains one of the most important modes of HBV transmission in this area. This cross-sectional survey examined the seroprevalence and knowledge of hepatitis B among pregnant women attending antenatal clinic (ANC) in a mission hospital in Ghana. Systematic sampling technique was used to recruit 196 pregnant women. The level of statistical significance was set at 0.05 alpha level. The hepatitis B prevalence estimate (hepatitis B surface antigen) was 10.2% (N = 20) and the entirety of the participants were aware of HBV infection. Majority cited media (radio) as their main source of information. Approximately 86% of the participants (N = 168) associated HBV infection with a curse and 88.8% (N = 174) indicated witches and wizards as possible causes of the infection. Those with higher level of school education had high hepatitis B knowledge score (P < 0.01). Implementation of a health education program on the route of hepatitis B transmission is required in the study setting. Also, inclusion of hepatitis B education as part of ANC activities will enable HBV-positive pregnant women to appreciate the need for hepatitis B vaccination of their newborns at birth.
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A Low-Cost, Community Knowledge Approach to Estimate Maternal and Jaundice-Associated Mortality in Rural Bangladesh
Available online: 08 October 2018More LessIn the absence of a civil registration system, a house-to-house survey is often used to estimate cause-specific mortality in low- and middle-income countries. However, house-to-house surveys are resource and time intensive. We applied a low-cost community knowledge approach to identify maternal deaths from any cause and jaundice-associated deaths among persons aged ≥ 14 years, and stillbirths and neonatal deaths in mothers with jaundice during pregnancy in five rural communities in Bangladesh. We estimated the method’s sensitivity and cost savings compared with a house-to-house survey. In the five communities with a total of 125,570 population, we identified 13 maternal deaths, 60 deaths among persons aged ≥ 14 years associated with jaundice, five neonatal deaths, and four stillbirths born to a mother with jaundice during pregnancy over the 3-year period before the survey using the community knowledge approach. The sensitivity of community knowledge method in identifying target deaths ranged from 80% for neonatal deaths to 100% for stillbirths and maternal deaths. The community knowledge approach required 36% of the staff time to undertake compared with the house-to-house survey. The community knowledge approach was less expensive but highly sensitive in identifying maternal and jaundice-associated mortality, as well as all-cause adult mortality in rural settings in Bangladesh. This method can be applied in rural settings of other low- and middle-income countries and, in conjunction with hospital-based hepatitis diagnoses, used to monitor the impact of programs to reduce the burden of cause-specific hepatitis mortality, a current World Health Organization priority.
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Antibodies in Melioidosis: The Role of the Indirect Hemagglutination Assay in Evaluating Patients and Exposed Populations
Available online: 08 October 2018More LessMelioidosis is a major neglected tropical disease with high mortality, caused by the Gram-negative bacterium Burkholderia pseudomallei (Bp). Microbiological culture remains the gold standard for diagnosis, but a simpler and more readily available test such as an antibody assay is highly desirable. In this study, we conducted a serological survey of blood donors (n = 1,060) and adult melioidosis patients (n = 200) in northeast Thailand to measure the antibody response to Bp using the indirect hemagglutination assay (IHA). We found that 38% of healthy adults (aged 17–59 years) have seropositivity (IHA titer ≥ 1:80). The seropositivity in healthy blood donors was associated with having a declared occupation of rice farmer and with residence in a nonurban area, but not with gender or age. In the melioidosis cohort, the seropositivity rate was higher in adult patients aged between 18 and 45 years (90%, 37/41) compared with those aged ≥ 45 years (68%, 108/159, P = 0.004). The seropositivity rate was significantly higher in people with diabetes (P = 0.008). Seropositivity was associated with decreased mortality on univariable analysis (P = 0.005), but not on multivariable analysis when adjusted for age, diabetes status, preexisting renal disease, and neutrophil count. This study confirms the presence of high background antibodies in an endemic region and demonstrates the limitations of using IHA during acute melioidosis in this population.
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Individual and Spatial Risk of Dengue Virus Infection in Puerto Maldonado, Peru
Available online: 08 October 2018More LessDengue virus (DENV) affects more than 100 countries worldwide. Dengue virus infection has been increasing in the southern Peruvian Amazon city of Puerto Maldonado since 2000. We designed this study to describe the prevalence of past DENV infection and to evaluate risk factors. In 2012, we conducted a cross-sectional serosurvey and administered a knowledge, attitudes, and practices (KAP) questionnaire to members of randomly selected households. Sera were screened for antibodies to DENV by ELISA and confirmed by plaque reduction neutralization test. We created indices for KAP (KAPi). We used SaTScan to detect clustering and created a multivariate model introducing the distance of households to potential vector and infection sources. A total of 505 participants from 307 households provided a blood sample and completed a questionnaire. Fifty-four percent of participants (95% CI: 49.6; 58.5) had neutralizing antibodies to DENV. Higher values of KAPi were positively associated with having DENV antibodies in the multivariate analysis (odds ratio [ORII]: 1.6, 95% CI: 0.6, 2.4; ORIII: 2.7, 95% CI: 1.3, 5.5; and ORIV: 2.4, 95% CI: 1.2, 5.0). Older groups had lower chances of having been exposed to DENV than younger people (OR20–30: 0.5, 95% CI: 0.2, 0.8; OR31–45: 0.5, 95% CI: 0.3, 0.9; and OR>45: 0.6, 95% CI: 0.3, 1.3). Multivariate data analysis from the 270 households with location information showed male gender to have lower risk of past DENV infection (OR: 0.6, 95% CI: 0.4, 0.9). We conclude that risk of DENV infection in Puerto Maldonado is related to gender, age of the population, and location.
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Soil-Transmitted Helminth Infections and Anemia in Schoolchildren from Corn Island Archipelago (RAAS, Nicaragua)
Available online: 08 October 2018More LessThe prevalence and intensity of soil-transmitted helminth (STH) infections in schoolchildren from Corn Islands (Nicaragua) were examined to detect mono- or poly-STH infected children, measuring different intensity levels, and to elucidate measurably increased odds of being anemic. A total of 341 stool samples provided by 2- to 15-year-old children were examined using a concentration technique and a Kato–Katz slide. Intensity of infection was expressed as eggs per gram (epg) of feces to classify light, moderate, or heavy intensity infection. A finger-prick blood sample was obtained from each student in the field. Soil-transmitted helminth prevalence was 54.3%, with Trichuris trichiura as the most prevalent species (48.9%). The combination T. trichiura/Ascaris lumbricoides (12.6%) was the most common. When T. trichiura or A. lumbricoides appeared as a single infection, light or moderate intensity infections were seen, whereas when multiple species were identified, heavy infections were present. Anemia was detected in those with any kind of STH infection (42.7%), with statistically significant differences (P = 0.004) when compared with uninfected individuals (28.2%). Polyparasite infection with one parasite species at moderate intensity and the other parasite species at light intensity or absent was found to be a significant factor for the odds of being anemic (odds ratio = 2.07). The present study reveals a high level of STH transmission requiring a deworming control program in Corn Islands and pointing to the need of improving the education and sanitary conditions of the population to avoid environmental contamination and reinfection.
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Alternate Anti-Leprosy Regimen for Multidrug Therapy Refractory Leprosy: A Retrospective Study from a Tertiary Care Center in North India
Available online: 08 October 2018More LessA subset of multibacillary (MB) leprosy patients manifest with clinical “nonresponsiveness” to the fixed-duration, World Health Organization multidrug therapy MB regimen (WHO-MDT-MBR). The aim of this retrospective study was to assess the effectiveness and safety of alternate anti-leprosy therapy (ALT) in such patients. This is an analysis of patients’ records, registered in the leprosy clinic of our institute over a period of 6 years (2010–2015). The criteria for inadequate response/nonresponsiveness to treatment were as follows: 1) persistent/new lesions after completing ≥ 12 months of WHO-MDT-MBR (isolated reactions were ruled out histopathologically) and 2) persistent positive/increasing value of the morphological index (MI) and a 2 log increase in the bacteriological index (BI) after ≥ 12 months of WHO-MDT-MBR. Such cases were treated with ALT consisting of minocycline, clofazimine, and ofloxacin (24 months). Of 556 patients registered during the study period, 40.3% (224) were slit-skin smear (SSS) positive and 59.7% (332) were SSS negative. Of all, 35 patients (6.3%) satisfied the criteria for clinical nonresponsiveness. Of 224 SSS-positive patients, these 35 patients amounted to 15.6%. The mean BI and MI of these patients after completion of ≥ 12 months of WHO-MDT-MBR were 5.3 ± 0.6 and 14 ± 6.8%, respectively. After 6 months of treatment with ALT, MI became negative (0) in all these patients. After completion of ALT, the mean BI and MI became 1.7 ± 0.7 and 0%, respectively (P < 0.0001). There were 16 patients with corticosteroid-dependent recurrent/chronic erythema nodosum leprosum, who had excellent response with significant reduction in the number of reactional episodes and mean dose of prednisolone required (P < 0.0001). No serious adverse effects were noted. We conclude that ALT is safe and effective in the management of MB leprosy patients who are nonresponsive to 12 months of WHO-MDT-MBR.
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Case Report: Concurrent Sympatric Scrub Typhus and Japanese Spotted Fever in Japan
Available online: 08 October 2018More LessScrub typhus and Japanese spotted fever—both rickettsial diseases—are endemic and notifiable in Japan and may cause a fatal outcome without prompt treatment. Here we present the first case of a concurrent sympatric infection of both diseases with grade II evidence. A 67-year-old woman, after a single event of potential exposure to the pathogens, presented with a 12-day history of fever, pharyngeal pain, papulo-erythematous rash, and pronounced fatigue. Her erythematous rash was distributed on her trunk and extremities, palms, and soles and eventually progressed to purpura. Fever persisted until doxycycline was administered on day 12. A significant > 4-fold increase in IgG and IgM titers against multiple serotypes of Orientia tsutsugamushi and Rickettsia japonica were revealed by indirect immunoperoxidase assays. These clinical and serological data, even in the absence of molecular or isolation evidence, provided grade II evidence that this was a concurrent infection of sympatric scrub typhus and Japanese spotted fever.
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Hymenolepis nana—An Emerging Intestinal Parasite Associated with Anemia in School Children from the Bolivian Chaco
Available online: 08 October 2018More LessTropical anemia can have multiple causes, whether socioeconomic, dietary, or infectious. In the Bolivian Chaco, soil-transmitted helminthiases (STH), malaria, and Chagas disease are potential infectious causes of anemia among school-aged children (SAC). Following years of preventive chemotherapy with mebendazole, the prevalence of STH among SAC living in that area is now negligible, whereas protozoan infections are still highly prevalent (81%); Hymenolepis nana is the most frequent intestinal helminth (∼13%). We present results of hemoglobin (Hb) assessment and the association between parasitic infections and Hb levels of that SAC population. Overall, 511 SAC (girls:boys ratio 1:1, mean age 9.4 years [95% confidence interval {CI}: 9.3–9.5]) had Hb levels measured by using a portable Hb system HB 301+ (HemoCue1 AB; Angelhome, Sweden). The prevalence of anemia was 23% (117/511), with mean and median Hb level = 12.2 g/dL (95% CI: 12.1–12.3; range 9.2–15.4 g/dL). By multivariate analysis, H. nana infection was associated with an increased risk of anemia (odds ratio 2.9, 95% CI: 1.5–5.7, P = 0.002). Two samples (0.5%) were positive for Trypanosoma cruzi and none for Plasmodium spp. by polymerase chain reaction of the 439 children tested. Anemia is still a concern among SAC living in the Bolivian Chaco. Our findings call for a greater attention to fecal–oral emerging pathogens, such as H. nana, and highlight the importance of water, sanitation, and hygiene improvements for disadvantaged population such as those living in the Bolivian Chaco.
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Entamoeba histolytica: Quantitative Proteomics Analysis Reveals Putative Virulence-Associated Differentially Abundant Membrane Proteins
Available online: 08 October 2018More LessEntamoeba histolytica is a protozoan parasite that causes amebiasis and poses a significant health risk for populations in endemic areas. The molecular mechanisms involved in the pathogenesis and regulation of the parasite are not well characterized. We aimed to identify and quantify the differentially abundant membrane proteins by comparing the membrane proteins of virulent and avirulent variants of E. histolytica HM-1:IMSS, and to investigate the potential associations among the differentially abundant membrane proteins. We performed quantitative proteomics analysis using isobaric tags for relative and absolute quantitation labeling, in combination with two mass spectrometry instruments, that is, nano-liquid chromatography (nanoLC)-MALDI-MS/MS and nanoLC-electrospray ionization tandem mass spectrometry. Overall, 37 membrane proteins were found to be differentially abundant, whereby 19 and 18 membrane proteins of the virulent variant of E. histolytica increased and decreased in abundance, respectively. Proteins that were differentially abundant include Rho family GTPase, calreticulin, a 70-kDa heat shock protein, and hypothetical proteins. Analysis by Protein ANalysis THrough Evolutionary Relationships DB revealed that the differentially abundant membrane proteins were mainly involved in catalytic activities (29.7%) and metabolic processes (32.4%). Differentially abundant membrane proteins that were found to be involved mainly in the catalytic activities and the metabolic processes were highlighted together with their putative roles in relation to the virulence. Further investigations should be performed to elucidate the roles of these proteins in E. histolytica pathogenesis.
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Enteric Fever in Cambodia: Community Perceptions and Practices Concerning Disease Transmission and Treatment
Available online: 08 October 2018More LessEnteric fever is a systemic bacterial infection in humans that is endemic in Cambodia and for which antibiotic resistance is increasingly reported. To guide public health programs, this qualitative study sought to explore community perceptions on transmission and treatment. Participant observation was carried out in hospital settings, pharmacies, and at a community level in Phnom Penh. In-depth interviews 39 and one focus group discussion were carried out with blood culture–confirmed enteric fever patients and purposively selected key informants. Informants were theoretically sampled based on initial themes identified using abductive analysis. Nvivo 11 was used for thematic coding. An urgent need to address health literacy concerning the transmission of enteric fever was identified, as lay informants did not link the disease and its symptoms to bacterial contamination of foods and drinks but rather to foods considered “bad” following humoral illness interpretations. As a result, lay informants considered recurrence of enteric fever preventable with appropriate dietary restrictions and Khmer traditional medicines. This study also reveals pluralistic health-care–seeking behavior. For initial and mild symptoms, patients preferred home treatment or traditional healing practices; limited household finances delayed treatment seeking. When symptoms persisted, patients first visited drug outlets or private practitioners, where they received a mix of nonessential medicines and one or more antibiotics often without prescription or confirmation of diagnosis. Inappropriate use of antibiotics was common and was related to diagnostic uncertainty and limited finances, factors which should be addressed during future efforts to improve the uptake of appropriate diagnostics and treatment of enteric fever.
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Visceral Leishmaniasis in the Muzaffapur Demographic Surveillance Site: A Spatiotemporal Analysis
Available online: 08 October 2018More LessIn the Indian subcontinent, visceral leishmaniasis (VL) has a strongly clustered distribution. The “index case approach” is promoted both for active case finding and indoor residual spraying (IRS). Uncertainty exists about the optimal radius. Buffer zones of 50–75 m around incident cases have been suggested for active case finding, for IRS the recommendation is to cover a radius of 500 m. Our aim was to establish optimal target areas both for IRS and for (re)active case finding. We plotted incident VL cases on a map per 6-month period (January–June or July–December) and drew buffers of 0 (same household), 50, 75, 100, 200, 300, 400, and 500 m around these cases. We then recorded total population and numbers of VL cases diagnosed over the next 6-month period in each of these buffers and beyond. We calculated incidence rate ratios (IRRs) using the population at more than 500 m from any case as reference category. There was a very strong degree of spatial clustering of VL with IRRs ranging from 45.2 (23.8–85.6) for those living in the same households to 14.6 (10.1–21.2) for those living within 75 m of a case diagnosed, during the previous period. Up to 500 m the IRR was still five times higher than that of the reference category. Our findings corroborate the rationale of screening not just household contacts but also those living within a perimeter of 50–75 m from an index case. For IRS, covering a perimeter of 500 m, appears to be a rational choice.
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Leptospirosis in French Historical Medical Literature: Weil’s Disease or Kelsch’s Disease?
Available online: 08 October 2018More LessEarly names for leptospirosis often indicate occupational or environmental exposure. Leptospirosis is hard to identify in the tropical setting because of co-circulating diseases. This is not the case in the temperate setting, such as Europe, where the few differential diagnoses at the time are malaria, typhoid, and viral hepatitis. Leptospirosis presumably caused community epidemics in Europe before 1900 and military epidemiologists carefully documented outbreaks in “constrained settings.” Achille Kelsch (1841–1911) synthesized available military data and epidemiological perspectives to define “epidemic jaundice” as a nosological continuum, caused by an infectious agent found in muds and water. He viewed Weil’s disease as being only one form of that now well-identified disease continuum. The causative pathogen and epidemiological determinants were identified years later. The role of soils and muds as intermediate reservoirs, as suggested by Kelsch, deserves further investigation.
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The Impact of Acquired Immune Deficiency Syndrome Treatment on Tuberculosis Detection at the National Level in South Africa
Available online: 01 October 2018More LessHuman immunodeficiency virus/Tuberculosis (HIV/TB) coinfection is particularly prevalent in South Africa, where TB has been the leading cause of death for more than a decade. The 2004–2008 national rollout of antiretroviral therapy (ART) provides a unique opportunity to examine the population-level impact of ART on the TB epidemic. We performed longitudinal regression analysis to follow the evolution of TB outcomes before and after the introduction of ART using a large data set from the National Health Laboratory Service. This is the first study to produce estimates of the impact of the ART rollout by exploiting staggered timing and geographic variation in the rollout. After ART became available in a health facility, 3.7% (P < 0.0001) more patients were tested for TB and 3.2% (P < 0.0001) more received repeat testing; however, there was a steep rise in testing before the introduction of ART. Although the number of TB-positive patients increased by 4.3% (P = 0.0002) in the first year post-ART, the TB rate among tested patients fell by 2% points (8%, P = 0.001) after 2 years. Sputum smear testing declined relative to more technologically advanced diagnostics post-ART. Antiretroviral therapy availability increased the attention to TB screening and drew new patients into the health-care system. Small increases in the numbers of repeat patients are indicative of retention in care. The decline in TB rates post-ART suggests that the reduction in TB risk due to improved immune functioning and health-care contact likely outweighed the increased TB risk because of the longer lifespan of ART initiators.
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Do Incarcerated Populations Serve as a Reservoir for Tuberculosis in South Africa?
Available online: 01 October 2018More LessTuberculosis (TB) prevalence among incarcerated populations is as much as 1,000 times higher than in the general population. This study evaluates whether correctional facilities serve as a reservoir through which TB is transmitted to surrounding communities. Tuberculosis test data were extracted from the South African National Health Laboratory Service database for patients tested for TB between 2005 and 2011. We conducted graphical analysis to assess the relationship of TB rates between incarcerated and non-incarcerated populations over time. We performed generalized linear modeling with a log link function to assess TB risk in communities surrounding correctional facilities, net of confounders. We assessed linkages between incarcerated and non-incarcerated populations over time using Granger causality analysis. Tuberculosis prevalence among incarcerated populations was four times higher than in the general population. Tuberculosis incidence rates in incarcerated and non-incarcerated populations followed similar trends over time. The presence of a correctional facility in a municipality was associated with 34.9% more detected TB cases (confidence interval: 11.6–63.2; P < 0.01), controlling for potential confounders. Detected TB in incarcerated populations did not have predictive power in explaining detected TB rates in the non-incarcerated population after controlling for serial correlation in the time series data. Despite high TB prevalence, trends in correctional facilities do not appear to be driving temporal trends in the general population. However, correctional facilities still act as a TB reservoir that raises the overall TB risk in the vicinity. Intensified TB control policies for correctional facilities, formerly incarcerated individuals, and surrounding communities will reduce TB prevalence overall.
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Case Report: Use of Plasma Exchange Followed by Convalescent Plasma Therapy in a Critically Ill Patient with Severe Fever and Thrombocytopenia Syndrome–Associated Encephalopathy: Cytokine/Chemokine Concentrations, Viral Loads, and Antibody Responses
Available online: 01 October 2018More LessWe describe the case of a patient with severe fever with thrombocytopenia syndrome (SFTS) complicated by SFTS-associated encephalopathy who was successfully treated with 4-day plasma exchange followed by two-time convalescent plasma therapy. During plasma exchange, the plasma cytokines IFN-α and IP-10 gradually decreased without change of plasma viral load. However, plasma viral load gradually decreased after convalescent plasma therapy. This case provides important insights for understanding the mechanisms of experimental therapy in severely affected SFTS patients.
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Case Report: Acute Transverse Myelitis after Zika Virus Infection
Available online: 01 October 2018More LessWe report here one case of Zika virus (ZIKV) infection associated with auto-immunity directed against the central nervous system in a Brazilian woman who developed acute transverse myelitis 9 days after recovery from an acute episode of fever with generalized erythema. Imaging of the spinal cord showed an elongated area on the T1–T10 level with gadolinium uptake. The diagnostic of the ZIKV infection was confirmed by cerebrospinal fluid and serum analysis. This patient had serum positivity for autoantibodies against myelin oligodendrocyte glycoprotein (MOG), a specific antibody against the myelin sheath. We propose that a direct central nervous system infection by ZIKV could lead to a specific auto-immunity against MOG protein.
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Case Report: Space-Occupying Lesion in the Liver Related to Preprandial Hunger and Hepatic Visceral Larva Migrans
Available online: 01 October 2018More LessVisceral larva migrans (VLM) is one of the clinical syndromes of human toxocariasis. We report a case of hepatic VLM presenting preprandial malaise and epigastric discomfort in a 58-year-old woman drinking raw roe deer blood. The imaging studies of the abdomen showed a 74-mm hepatic mass featuring hepatic VLM. Anti–Toxocara canis IgG was observed in enzyme-linked immunosorbent assay (ELISA) and western blot. Despite anthelmintic treatment, the patient complained of newly developed cough and skin rash with severe eosinophilia. Hepatic lesion increased in size. The patient underwent an open left lobectomy of the liver. After the surgery, the patient was free of symptoms such as preprandial malaise, epigastric discomfort, cough, and skin rash. Laboratory test showed a normal eosinophilic count at postoperative 1 month, 6 months, 1 year, and 4 years. The initial optical density value of 2.55 of anti–T. canis IgG in ELISA was found to be negative (0.684) at postoperative 21 months. Our case report highlights that a high degree of clinical suspicion for hepatic VLM should be considered in a patient with a history of ingestion of raw food in the past, presenting severe eosinophilia and a variety of symptoms which reflect high worm burdens. Symptom remission, eosinophilia remission, and complete radiological resolution of lesions can be complete with surgery.
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Case Report: Squamous Cell Carcinoma Referred for Mohs Surgery Found to be Cutaneous Leishmaniasis
Available online: 01 October 2018More LessChronic skin lesions constitute a clinical diagnostic challenge. We report the case of a patient whose facial lesion was histopathologically compatible with squamous cell carcinoma and hence programmed for Mohs surgery. However, review of the clinical and epidemiological history led to laboratory diagnosis of cutaneous leishmaniasis, treatment with miltefosine, and complete resolution of the lesion.
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Impact of a Nonfatal Dengue Episode on Disability-Adjusted Life Years: A Systematic Analysis
Available online: 01 October 2018More LessAs dengue causes about 4,000 symptomatic nonfatal episodes for every dengue death globally, quantitative disability assessments are critical to assess the burden of dengue and the cost-effectiveness of dengue control interventions. This systematic analysis of disability or quality of life lost from a symptomatic nonfatal dengue episode combined a systematic literature review, statistical modeling, and probabilistic sensitivity analyses. We conceptualized a dengue episode as having two phases: acute and persistent symptoms. Our estimates for the acute phase, consisting of onset and recovery periods and defined as the first 20 days (0.054 year), were based on literature review. We searched PubMed, POPLINE, EconLit, Google Scholar, scientific conferences, and other sources, for “dengue” plus “quality of life” or related terms. From 4,322 initial entries, six met our criteria (original studies with empirical data). The median disability-adjusted life year (DALY) burden for the acute phase was 0.011 (95% certainty interval [CI]: 0.006–0.015) for ambulatory episodes, 0.015 (CI: 0.010–0.020) for hospitalized episodes, and 0.012 (CI: 0.006–0.019) overall. Using literature reviews about persistent dengue, we estimated that 34% of episodes experienced persistent symptoms with a median duration of symptoms of 0.087 (CI: 0.040–0.359) year, which resulted in median DALYs of 0.019 (CI: 0.008–0.082). Thus, the overall median DALY burden was 0.031 (CI: 0.017–0.092) for ambulatory episodes, 0.035 (CI: 0.024–0.096) for hospitalized episodes, and 0.032 (CI: 0.018–0.093) overall. Our dengue-specific burden of a dengue episode was 2.1 times the 2013 Global Burden of Disease estimate. These literature-based estimates provide an empirical summary for policy and cost-effectiveness analyses.
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Integrating Blood Collection within Household Surveys: Lessons Learned from Nesting a Measles and Rubella Serological Survey within a Post-Campaign Coverage Evaluation Survey in Southern Province, Zambia
Available online: 01 October 2018More LessAge-specific population immunity to many vaccine-preventable diseases can be measured using serological surveys. However, stand-alone serological surveys are infrequently conducted in low- and middle-income countries because of costs, operational challenges, and potential high refusal rates for blood collection. Nesting a serosurvey within a household cluster survey may overcome some of these challenges. We share lessons learned from nesting a serosurvey within a measles and rubella vaccination post-campaign coverage evaluation survey (PCES). In 15 of the 26 PCES clusters in Southern Province, Zambia, we collected dried blood spots from 581 participants aged 9 months and older. Household participation rates for the main PCES were higher in the serosurvey clusters (86%) than PCES-only clusters (71%), suggesting that a serosurvey can be successfully integrated without adversely affecting PCES participation. Among households that participated in the PCES, 80% also participated in the serosurvey and 86% of individuals available in the household provided a blood sample for the serosurvey. Substantial planning and coordination, additional staff training, and community mobilization were critical to the success of the serosurvey. Most challenges stemmed from using different data collecting tools and teams for the serosurvey and PCES. A more efficient design would be to fully integrate the serosurvey by adding blood collection and additional questions to the PCES.
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Case Report: Strongyloides stercoralis Hyperinfection in a Patient with HTLV-1: A Case Report of an Infection with Filariform and Rhabditiform Larvae, Eggs, and Free-Living Adult Females
Available online: 01 October 2018More LessStrongyloides stercoralis is the main etiological agent of human strongyloidiasis. Severe strongyloidiasis is commonly associated to alcoholism, corticostereoid use, and human T cell lymphotropic virus type 1 (HTLV-1) coinfection. Herein, we report a case of a 13-year-old boy coinfected with S. stercoralis and HTLV-1, excreting several parasitic forms in the stool. The parasitological examination of his feces showed a large amount of filariform (about 3,000 larvae per gram of feces) and rhabditiform larvae (about 2,000 larvae per gram of feces). In addition, free-living adult females (about 50 parasites per gram of feces) and eggs (about 60 eggs per gram of feces) were detected. The main laboratory findings pointed to high IgE levels (228 UI/mL) and eosinophila (11.6%). The patient was treated with three courses of ivermectin (200 µg/kg twice, 2 weeks apart), achieving the parasitological cure. An increase of about 19 times in IL-17 level was observed following the parasitological cure, in addition to a decrease in the white blood cell, eosinophil counts, and IgE levels. This is the first case report, to our knowledge, in which an S. stercoralis adult free-living female was described in human feces and where an increase in IL-17 levels after Strongyloides treatment in a HTLV-1 coinfected individual was observed. This finding raises the need for further studies about IL-17 immunomodulation in S. stercoralis and HTLV-1 coinfected patients.
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Evidence of Likely Autochthonous Transmission of Chagas Disease in Arizona
Available online: 01 October 2018More LessA healthy 16-year-old girl born and raised in Tucson, AZ, had screening and confirmatory testing revealing Chagas disease; clinical evaluation established that she had the indeterminate form of chronic Chagas disease with evidence of likely autochthonous transmission. Trypanosoma cruzi DNA was detected by conventional PCR in Triatoma rubida captured at her home.
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Sensitivity of the Point-of-Care Circulating Cathodic Antigen Urine Cassette Test for Diagnosis of Schistosoma mansoni in Low-Endemicity Settings in Côte d’Ivoire
Available online: 01 October 2018More LessThe sensitivity of a point-of-care circulating cathodic antigen (POC-CCA) urine cassette test for diagnosis of Schistosoma mansoni in low-endemicity settings is poorly understood. We conducted a cross-sectional survey in 14 villages in western Côte d’Ivoire and diagnosed children aged 9–12 years for schistosomiasis. Two stool samples were subjected to triplicate Kato–Katz thick smears each for diagnosis of S. mansoni, whereas a single urine sample was examined by POC-CCA for S. mansoni, filtration for Schistosoma haematobium, and reagent strip for microhematuria. According to the Kato–Katz technique, we found 45 out of 681 children positive for S. mansoni (6.6%) with a mean intensity among infected children of 72.2 eggs per gram of stool. Point-of-care circulating cathodic antigen revealed a prevalence of S. mansoni of 33.0% when trace results were considered positive and 12.4% when trace results were considered negative. Eggs of S. haematobium were found in eight participants (1.2%), whereas the prevalence of microhematuria was 13.5%. A single POC-CCA urine cassette test revealed a several-fold higher prevalence of S. mansoni than multiple Kato–Katz thick smears in this low-endemicity area. Our findings have important ramifications for choosing an appropriate diagnostic tool in low-endemic areas that might be targeted for elimination.
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Absence of Plasmodium falciparum K13 Propeller Domain Polymorphisms among Field Isolates Collected from the Brazilian Amazon Basin between 1984 and 2011
Available online: 01 October 2018More LessArtemisinin resistance, presently confined to Southeast Asia and associated with mutations in the Plasmodium falciparum K13 (PfK13) propeller domain, represents a serious threat to global malaria control. This study aimed to provide baseline information for future artemisinin resistance surveillance, by analyzing the PfK13 propeller domain in P. falciparum field isolates collected from the Brazilian Amazon Basin between 1984 and 2011. A total of 152 P. falciparum mono-infections were assessed, of which 118 (78%) were collected before and 34 (22%) after the introduction of artemisinin-based combination therapy (ACT) in 2006. An 849-base pair fragment encoding the PfK13 propeller was amplified by nested PCR and sequenced in both directions. The sequences were compared with the reference sequence of P. falciparum 3D7. All samples showed wild-type sequences, thus, no mutations were observed. The results are in agreement with other recent reports and do not provide evidence for presence of PfK13 propeller domain polymorphisms associated with artemisinin resistance among P. falciparum field isolates in the Brazilian Amazon Basin neither before nor after the implementation of ACT.
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Case Report: Subcutaneous Ivermectin Pharmacokinetics in Disseminated Strongyloides Infection: Plasma and Postmortem Analysis
Available online: 17 September 2018More LessParenteral ivermectin treatment of disseminated strongyloidiasis and hyperinfection is increasing, although not licensed in humans and with limited pharmacokinetic data available. Plasma and postmortem tissue analysis in an HIV/hepatitis C virus–positive man with disseminated strongyloidiasis suggests loading subcutaneous ivermectin doses are required, from which the central nervous system is protected.
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Molecular Identification of Onchocerca spp. Larvae in Simulium damnosum sensu lato Collected in Northern Uganda
Available online: 02 October 2017More LessPrevious 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.
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