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Human macrophages differentiated in the presence of vitamin D<sub>3</sub> restrict dengue virus infection and innate responses by downregulating mannose receptor expression

PLoS Neglected Tropical Diseases News - 11 October 2017 - 9:00pm

by John F. Arboleda Alzate, Izabela A. Rodenhuis-Zybert, Juan C. Hernández, Jolanda M. Smit, Silvio Urcuqui-Inchima

Background

Severe dengue disease is associated with high viral loads and overproduction of pro-inflammatory cytokines, suggesting impairment in the control of dengue virus (DENV) and the mechanisms that regulate cytokine production. Vitamin D3 has been described as an important modulator of immune responses to several pathogens. Interestingly, increasing evidence has associated vitamin D with decreased DENV infection and early disease recovery, yet the molecular mechanisms whereby vitamin D reduces DENV infection are not well understood.

Methods and principal findings

Macrophages represent important cell targets for DENV replication and consequently, they are key drivers of dengue disease. In this study we evaluated the effect of vitamin D3 on the differentiation of monocyte-derived macrophages (MDM) and their susceptibility and cytokine response to DENV. Our data demonstrate that MDM differentiated in the presence of vitamin D3 (D3-MDM) restrict DENV infection and moderate the classical inflammatory cytokine response. Mechanistically, vitamin D3-driven differentiation led to reduced surface expression of C-type lectins including the mannose receptor (MR, CD206) that is known to act as primary receptor for DENV attachment on macrophages and to trigger of immune signaling. Consequently, DENV bound less efficiently to vitamin D3-differentiated macrophages, leading to lower infection. Interestingly, IL-4 enhanced infection was reduced in D3-MDM by restriction of MR expression. Moreover, we detected moderate secretion of TNF-α, IL-1β, and IL-10 in D3-MDM, likely due to less MR engagement during DENV infection.

Conclusions/Significance

Our findings reveal a molecular mechanism by which vitamin D counteracts DENV infection and progression of severe disease, and indicates its potential relevance as a preventive or therapeutic candidate.

Albendazole and ivermectin for the control of soil-transmitted helminths in an area with high prevalence of <i>Strongyloides stercoralis</i> and hookworm in northwestern Argentina: A community-based pragmatic study

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Adriana Echazú, Marisa Juarez, Paola A. Vargas, Silvana P. Cajal, Ruben O. Cimino, Viviana Heredia, Silvia Caropresi, Gladys Paredes, Luis M. Arias, Marcelo Abril, Silvia Gold, Patrick Lammie, Alejandro J. Krolewiecki

Background

Recommendations for soil-transmitted helminth (STH) control give a key role to deworming of school and pre-school age children with albendazole or mebendazole; which might be insufficient to achieve adequate control, particularly against Strongyloides stercoralis. The impact of preventive chemotherapy (PC) against STH morbidity is still incompletely understood. The aim of this study was to assess the effectiveness of a community-based program with albendazole and ivermectin in a high transmission setting for S. stercoralis and hookworm.

Methodology

Community-based pragmatic trial conducted in Tartagal, Argentina; from 2012 to 2015. Six communities (5070 people) were enrolled for community-based PC with albendazole and ivermectin. Two communities (2721 people) were re-treated for second and third rounds. STH prevalence, anemia and malnutrition were explored through consecutive surveys. Anthropometric assessment of children, stool analysis, complete blood count and NIE-ELISA serology for S. stercoralis were performed.

Principal findings

STH infection was associated with anemia and stunting in the baseline survey that included all communities and showed a STH prevalence of 47.6% (almost exclusively hookworm and S. stercoralis). Among communities with multiple interventions, STH prevalence decreased from 62% to 23% (p<0.001) after the first PC; anemia also diminished from 52% to 12% (p<0.001). After two interventions S. stercoralis seroprevalence declined, from 51% to 14% (p<0.001) and stunting prevalence decreased, from 19% to 12% (p = 0.009).

Conclusions

Hookworm’ infections are associated with anemia in the general population and nutritional impairment in children. S. stercoralis is also associated with anemia. Community-based deworming with albendazole and ivermectin is effective for the reduction of STH prevalence and morbidity in communities with high prevalence of hookworm and S. stercoralis.

T-cell regulation in Erythema Nodosum Leprosum

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Edessa Negera, Steven L. Walker, Kidist Bobosha, Rawleigh Howe, Abraham Aseffa, Hazel M. Dokrell, Diana N. Lockwood

Leprosy is a disease caused by Mycobacterium leprae where the clinical spectrum correlates with the patient immune response. Erythema Nodosum Leprosum (ENL) is an immune-mediated inflammatory complication, which causes significant morbidity in affected leprosy patients. The underlying cause of ENL is not conclusively known. However, immune-complexes and cell-mediated immunity have been suggested in the pathogenesis of ENL. The aim of this study was to investigate the regulatory T-cells in patients with ENL. Forty-six untreated patients with ENL and 31 non-reactional lepromatous leprosy (LL) patient controls visiting ALERT Hospital, Ethiopia were enrolled to the study. Blood samples were obtained before, during and after prednisolone treatment of ENL cases. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of regulatory T-cells by flow cytometry. Five markers: CD3, CD4 or CD8, CD25, CD27 and FoxP3 were used to define CD4+ and CD8+ regulatory T-cells. Clinical and histopathological data were obtained as supplementary information. All patients had been followed for 28 weeks. Patients with ENL reactions had a lower percentage of CD4+ regulatory T-cells (1.7%) than LL patient controls (3.8%) at diagnosis of ENL before treatment. After treatment, the percentage of CD4+regulatory T-cells was not significantly different between the two groups. The percentage of CD8+ regulatory T-cells was not significantly different in ENL and LL controls before and after treatment. Furthermore, patients with ENL had higher percentage of CD4+ T-ells and CD4+/CD8+ T-cells ratio than LL patient controls before treatment. The expression of CD25 on CD4+ and CD8+ T-cells was not significantly different in ENL and LL controls suggesting that CD25 expression is not associated with ENL reactions while FoxP3 expression on CD4+ T-cells was significantly lower in patients with ENL than in LL controls. We also found that prednisolone treatment of patients with ENL reactions suppresses CD4+ T-cell but not CD8+ T-cell frequencies. Hence, ENL is associated with lower levels of T regulatory cells and higher CD4+/CD8+ T-cell ratio. We suggest that this loss of regulation is one of the causes of ENL.

Characterization of the catalytic center of the Ebola virus L polymerase

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Marie Luisa Schmidt, Thomas Hoenen

Background

Ebola virus (EBOV) causes a severe hemorrhagic fever in humans and non-human primates. While no licensed therapeutics are available, recently there has been tremendous progress in developing antivirals. Targeting the ribonucleoprotein complex (RNP) proteins, which facilitate genome replication and transcription, and particularly the polymerase L, is a promising antiviral approach since these processes are essential for the virus life cycle. However, until now little is known about L in terms of its structure and function, and in particular the catalytic center of the RNA-dependent RNA polymerase (RdRp) of L, which is one of the most promising molecular targets, has never been experimentally characterized.

Methodology/Principal findings

Using multiple sequence alignments with other negative sense single-stranded RNA viruses we identified the putative catalytic center of the EBOV RdRp. An L protein with mutations in this center was then generated and characterized using various life cycle modelling systems. These systems are based on minigenomes, i.e. miniature versions of the viral genome, in which the viral genes are exchanged against a reporter gene. When such minigenomes are coexpressed with RNP proteins in mammalian cells, the RNP proteins recognize them as authentic templates for replication and transcription, resulting in reporter activity reflecting these processes. Replication-competent minigenome systems indicated that our L catalytic domain mutant was impaired in genome replication and/or transcription, and by using replication-deficient minigenome systems, as well as a novel RT-qPCR-based genome replication assay, we showed that it indeed no longer supported either of these processes. However, it still showed similar expression to wild-type L, and retained its ability to be incorporated into inclusion bodies, which are the sites of EBOV genome replication.

Conclusions/Significance

We have experimentally defined the catalytic center of the EBOV RdRp, and thus a promising antiviral target regulating an essential aspect of the EBOV life cycle.

Application of a loop-mediated isothermal amplification (LAMP) assay targeting <i>cox1</i> gene for the detection of <i>Clonorchis sinensis</i> in human fecal samples

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by S. M. Mazidur Rahman, Hyun Beom Song, Yan Jin, Jin-Kyoung Oh, Min Kyung Lim, Sung-Tae Hong, Min-Ho Choi

Background

Clonorchiasis is prevalent in the Far East, and a major health problem in endemic areas. Infected persons may experience, if not treated, serious complications such as bile stone formation, pyogenic cholangitis, and even cholangiocarcinoma. Early diagnosis and treatment are important to prevent serious complications and, therefore, the simple and reliable diagnostic method is necessary to control clonorchiasis in endemic areas, where resources for the diagnosis are limited.

Methodology/Principle findings

The loop-mediated isothermal amplification (LAMP) assay has been applied for the detection of Clonorchis sinensis DNA. Six primers targeting eight locations on the cytochrome c oxidase subunit 1 gene of C. sinensis were designed for species-specific amplification using the LAMP assay. The LAMP assay was sensitive enough to detect as little as 100 fg of C. sinensis genomic DNA and the detection limit in 100 mg of stool was as low as one egg. The assay was highly specific because no cross-reactivity was observed with the DNA of other helminths, protozoa or Escherichia coli. Then, LAMP assay was applied to human fecal samples collected from an endemic area of clonorchiasis in Korea. Using samples showing consistent results by both Kato-Katz method and real-time PCR as reference standards, the LAMP assay showed 97.1% (95% CI, 90.1–99.2) of sensitivity and 100% (95% CI, 92.9–100) of specificity. In stool samples with more than 100 eggs per gram of feces, the sensitivity achieved 100%.

Conclusions

To detect C. sinensis in human fecal samples, the LAMP assay was applied and achieved high sensitivity and specificity. The LAMP assay can be utilized in field laboratories as a powerful tool for diagnosis and epidemiological survey of clonorchiasis.

Mitochondrial dual-coding genes in <i>Trypanosome brucei</i>

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Laura E. Kirby, Donna Koslowsky

Trypanosoma brucei is transmitted between mammalian hosts by the tsetse fly. In the mammal, they are exclusively extracellular, continuously replicating within the bloodstream. During this stage, the mitochondrion lacks a functional electron transport chain (ETC). Successful transition to the fly, requires activation of the ETC and ATP synthesis via oxidative phosphorylation. This life cycle leads to a major problem: in the bloodstream, the mitochondrial genes are not under selection and are subject to genetic drift that endangers their integrity. Exacerbating this, T. brucei undergoes repeated population bottlenecks as they evade the host immune system that would create additional forces of genetic drift. These parasites possess several unique genetic features, including RNA editing of mitochondrial transcripts. RNA editing creates open reading frames by the guided insertion and deletion of U-residues within the mRNA. A major question in the field has been why this metabolically expensive system of RNA editing would evolve and persist. Here, we show that many of the edited mRNAs can alter the choice of start codon and the open reading frame by alternative editing of the 5’ end. Analyses of mutational bias indicate that six of the mitochondrial genes may be dual-coding and that RNA editing allows access to both reading frames. We hypothesize that dual-coding genes can protect genetic information by essentially hiding a non-selected gene within one that remains under selection. Thus, the complex RNA editing system found in the mitochondria of trypanosomes provides a unique molecular strategy to combat genetic drift in non-selective conditions.

Health-related impact on quality of life and coping strategies for chikungunya: A qualitative study in Curaçao

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Jelte Elsinga, Martin P. Grobusch, Adriana Tami, Izzy Gerstenbluth, Ajay Bailey

Introduction

Chikungunya is an emerging public health problem in tropical and subtropical regions, due to ongoing transmission and its incapacitating acute disease phase, and chronic sequelae. The disease is responsible for a major impact on Health Related Quality of Life (HRQoL), which may last several years. To our knowledge, this study is the first qualitative examination of HRQoL and coping strategies of chikungunya-infected individuals.

Methods

Qualitative research methods consisted of 20 in-depth interviews and seven Focus Group Discussions (FGDs), n = 50. Analysis was based on the principles of the grounded theory.

Results

Different impacts on HRQoL were reported. The physical and emotional domains of the HRQoL were mainly affected by chikungunya, while social and individual financial consequences were limited. Individual financial impact was limited through the universal health care program of Curaçao. Long-term lingering musculoskeletal and other manifestations caused significant pain and limited mobility. Hence, participants experienced dependency, impairment of normal daily life activities, moodiness, hopelessness, a change of identity, and insecurity about their future. The unpredictable nature and consequences of chikungunya gave rise to various coping strategies. Problem-focused coping styles led to higher uptake of medical care and were linked to more negative impact of HRQoL, whereas emotional coping strategies focusing on acceptance of the situation were linked to less uptake of medical care and more positive impact on HRQoL.

Conclusions

This study provides an in-depth understanding of acute and long-term HRQoL impact of chikungunya. The results can better inform health promotion policies and interventions. Messages to the public should focus on promoting healthy and efficient coping strategies, in order to prevent additional stress in affected individuals.

Next-generation ELISA diagnostic assay for Chagas Disease based on the combination of short peptidic epitopes

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Juan Mucci, Santiago J. Carmona, Romina Volcovich, Jaime Altcheh, Estefanía Bracamonte, Jorge D. Marco, Morten Nielsen, Carlos A. Buscaglia, Fernán Agüero

Chagas Disease, caused by the protozoan Trypanosoma cruzi, is a major health and economic problem in Latin America for which no vaccine or appropriate drugs for large-scale public health interventions are yet available. Accurate diagnosis is essential for the early identification and follow up of vector-borne cases and to prevent transmission of the disease by way of blood transfusions and organ transplantation. Diagnosis is routinely performed using serological methods, some of which require the production of parasite lysates, parasite antigenic fractions or purified recombinant antigens. Although available serological tests give satisfactory results, the production of reliable reagents remains laborious and expensive. Short peptides spanning linear B-cell epitopes have proven ideal serodiagnostic reagents in a wide range of diseases. Recently, we have conducted a large-scale screening of T. cruzi linear B-cell epitopes using high-density peptbide chips, leading to the identification of several hundred novel sequence signatures v associated to chronic Chagas Disease. Here, we performed a serological assessment of 27 selected epitopes and of their use in a novel multipeptide-based diagnostic method. A combination of 7 of these peptides were finally evaluated in ELISA format against a panel of 199 sera samples (Chagas-positive and negative, including sera from Leishmaniasis subjects). The multipeptide formulation displayed a high diagnostic performance, with a sensitivity of 96.3% and a specificity of 99.15%. Therefore, the use of synthetic peptides as diagnostic tools are an attractive alternative in Chagas’ disease diagnosis.

Epidemiological consequences of immune sensitisation by pre-exposure to vector saliva

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Tsukushi Kamiya, Megan A. Greischar, Nicole Mideo

Blood-feeding arthropods—like mosquitoes, sand flies, and ticks—transmit many diseases that impose serious public health and economic burdens. When a blood-feeding arthropod bites a mammal, it injects saliva containing immunogenic compounds that facilitate feeding. Evidence from Leishmania, Plasmodium and arboviral infections suggests that the immune responses elicited by pre-exposure to arthropod saliva can alter disease progression if the host later becomes infected. Such pre-sensitisation of host immunity has been reported to both exacerbate and limit infection symptoms, depending on the system in question, with potential implications for recovery. To explore if and how immune pre-sensitisation alters the effects of vector control, we develop a general model of vector-borne disease. We show that the abundance of pre-sensitised infected hosts should increase when control efforts moderately increase vector mortality rates. If immune pre-sensitisation leads to more rapid clearance of infection, increasing vector mortality rates may achieve greater than expected disease control. However, when immune pre-sensitisation prolongs the duration of infection, e.g., through mildly symptomatic cases for which treatment is unlikely to be sought, vector control can actually increase the total number of infected hosts. The rising case burden may go unnoticed unless active surveillance methods are used to detect such sub-clinical individuals, who could provide long-lasting reservoirs for transmission and suffer long-term health consequences of those sub-clinical infections. Sensitivity analysis suggests that these negative consequences could be mitigated through integrated vector management. While the effect of saliva pre-exposure on acute symptoms is well-studied for leishmaniasis, the immunological and clinical consequences are largely uncharted for other vector-parasite-host combinations. We find a large range of plausible epidemiological outcomes, positive and negative for public health, underscoring the need to quantify how immune pre-sensitisation modulates recovery and transmission rates in vector-borne diseases.

Sanitation, hookworm, anemia, stunting, and wasting in primary school children in southern Ethiopia: Baseline results from a study in 30 schools

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Jack E. T. Grimes, Gemechu Tadesse, Iain A. Gardiner, Elodie Yard, Yonas Wuletaw, Michael R. Templeton, Wendy E. Harrison, Lesley J. Drake

Background

Inadequate nutrition; neglected topical diseases; and insufficient water, sanitation, and hygiene (WASH) are interrelated problems in schools in low-income countries, but are not routinely tackled together. A recent three-year longitudinal study investigated integrated school health and nutrition approaches in 30 government primary schools in southern Ethiopia. Here, we report on baseline associations between sanitation, hookworm infection, anemia, stunting, and wasting.

Methods

In each school, the Schistosoma mansoni, S. haematobium, and soil-transmitted helminth infection intensities; blood hemoglobin concentrations; heights; and weights of approximately 125 students were assessed. Of these 125 students, approximately 20 were randomly selected for student WASH surveys. Of these 20, approximately 15 were randomly selected for household sanitation observations. School WASH was also assessed through a combination of observations and questions to the headteacher. Mixed-effects logistic regression was used to compare household sanitation with hookworm infection (the other parasites being much less prevalent); and hookworm infection with anemia, stunting, and wasting.

Findings

Blood, stool, and urine samples were provided by 3,729 children, and student WASH and household WASH surveys were conducted with 596 and 448 of these students, respectively.Hookworm, Ascaris lumbricoides, Trichuris trichiura, and S. mansoni infections had prevalences of 18%, 4.8%, 0.6%, and 0.3%, respectively, and no S. haematobium infections were found. Anemia, stunting, and wasting had prevalences of 23%, 28%, and 14%, respectively.No statistically significant associations were found between latrine absence or evidence of open defecation at home, and hookworm infection (adjusted odds ratio, OR = 1.28, 95% confidence interval, CI: 0.476–3.44; and adjusted OR = 1.21, 95% CI: 0.468–3.12; respectively); or between hookworm infection and anemia, stunting, or wasting (adjusted OR = 1.24, 95% CI: 0.988–1.57; adjusted OR = 0.992, 95% CI: 0.789–1.25; and adjusted OR = 0.969, 95% CI: 0.722–1.30; respectively).

Conclusions

In this setting, no statistically significant associations were found between sanitation and hookworm; or between hookworm and anemia, stunting, or wasting. More evidence on best practices for integrated school health interventions will be gathered from the follow-up surveys in this study.

How does competition among wild type mosquitoes influences the performance of <i>Aedes aegypti</i> and dissemination of <i>Wolbachia pipientis</i>?

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Suellen de Oliveira, Daniel Antunes Maciel Villela, Fernando Braga Stehling Dias, Luciano Andrade Moreira, Rafael Maciel de Freitas

Background

Wolbachia has been deployed in several countries to reduce transmission of dengue, Zika and chikungunya viruses. During releases, Wolbachia-infected females are likely to lay their eggs in local available breeding sites, which might already be colonized by local Aedes sp. mosquitoes. Therefore, there is an urgent need to estimate the deleterious effects of intra and interspecific larval competition on mosquito life history traits, especially on the duration of larval development time, larval mortality and adult size.

Methodology/principal findings

Three different mosquito populations were used: Ae. aegypti infected with Wolbachia (wMelBr strain), wild Ae. aegypti and wild Ae. albopictus. A total of 21 treatments explored intra and interspecific larval competition with varying larval densities, species proportions and food levels. Each treatment had eight replicates with two distinct food levels: 0.25 or 0.50 g of Chitosan and fallen avocado leaves. Overall, overcrowding reduced fitness correlates of the three populations. Ae. albopictus larvae presented lower larval mortality, shorter development time to adult and smaller wing sizes than Ae. aegypti. The presence of Wolbachia had a slight positive effect on larval biology, since infected individuals had higher survivorship than uninfected Ae. aegypti larvae.

Conclusions/significance

In all treatments, Ae. albopictus outperformed both wild Ae. aegypti and the Wolbachia-infected group in larval competition, irrespective of larval density and the amount of food resources. The major force that can slow down Wolbachia invasion is the population density of wild mosquitoes. Given that Ae. aegypti currently dominates in Rio, in comparison with Ae. albopictus frequency, additional attention must be given to the population density of Ae. aegypti during releases to increase the likelihood of Wolbachia invasion.

Insights and efforts to control rabies in Zambia: Evaluation of determinants and barriers to dog vaccination in Nyimba district

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Carolyn Patricia Mulipukwa, Boyd Mudenda, Allan Rabson Mbewe

Background

The current rabies control strategy in Zambia is based on dog vaccination, dog population control and dog movement restrictions. In Nyimba district of Zambia, dog vaccination coverage is low but the incidence of dog bites is high which places the community at risk of rabies infection. The renewed global interest eliminating rabies in developing countries has spurred interest to identify determinants and barriers of dog vaccination in an effort to reduce the overall disease burden.

Methodology

A mixed methods cross sectional design was used in the study. This consisted of three parts: Evaluation of medical records regarding dog bite injuries, implementation and analysis of a household survey and in-depth review of key informant interviews. Data was collected into a Microsoft Excel database and subsequently transferred to STATA for descriptive, inferential and thematic analysis.

Results

Dog vaccination coverage overall was 8.7% (57/655), with 3.4% (22/655) in urban areas, 1.8% (12/655) in peri-urban and 3.5 (23/655) in the rural regions. Financially stable households were more likely to have their dogs vaccinated. Only 10.3% (31/300) of the respondents had vaccinated their dogs and these had a reliable source of income as 6% (18/300) were peasant farmers, 2% (6/300) were dependants whose guardians were financially stable and 2.3% (7/300) were in steady employment. Important barriers to dog vaccination included cost, limited awareness of vaccination program and access.

Conclusion

Current rabies control strategies in Nyimba district, Zambia, appear quite limited. Improvements in the regional dog vaccination program may provide benefits. Enhancement of educational efforts targeting behavioural factors may also prove useful. Finally, the cost of dog vaccination can be reduced with scaled up production of a local vaccine.

Multi-site cholera surveillance within the African Cholera Surveillance Network shows endemicity in Mozambique, 2011–2015

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Cynthia Semá Baltazar, José Paulo Langa, Liliana Dengo Baloi, Richard Wood, Issaka Ouedraogo, Berthe-Marie Njanpop-Lafourcade, Dorteia Inguane, Jucunu Elias Chitio, Themba Mhlanga, Lorna Gujral, Bradford D. Gessner, Aline Munier, Martin A. Mengel

Background

Mozambique suffers recurrent annual cholera outbreaks especially during the rainy season between October to March. The African Cholera Surveillance Network (Africhol) was implemented in Mozambique in 2011 to generate accurate detailed surveillance data to support appropriate interventions for cholera control and prevention in the country.

Methodology/Principal findings

Africhol was implemented in enhanced surveillance zones located in the provinces of Sofala (Beira), Zambézia (District Mocuba), and Cabo Delgado (Pemba City). Data were also analyzed from the three outbreak areas that experienced the greatest number of cases during the time period under observation (in the districts of Cuamba, Montepuez, and Nampula). Rectal swabs were collected from suspected cases for identification of Vibrio cholerae, as well as clinical, behavioral, and socio-demographic variables. We analyzed factors associated with confirmed, hospitalized, and fatal cholera using multivariate logistic regression models.A total of 1,863 suspected cases and 23 deaths (case fatality ratio (CFR), 1.2%) were reported from October 2011 to December 2015. Among these suspected cases, 52.2% were tested of which 23.5% were positive for Vibrio cholerae O1 Ogawa. Risk factors independently associated with the occurrence of confirmed cholera were living in Nampula city district, the year 2014, human immunodeficiency virus infection, and the primary water source for drinking.

Conclusions/Significance

Cholera was endemic in Mozambique during the study period with a high CFR and identifiable risk factors. The study reinforces the importance of continued cholera surveillance, including a strong laboratory component. The results enhanced our understanding of the need to target priority areas and at-risk populations for interventions including oral cholera vaccine (OCV) use, and assess the impact of prevention and control strategies. Our data were instrumental in informing integrated prevention and control efforts during major cholera outbreaks in recent years.

Prevalence, intensity and risk factors of tungiasis in Kilifi County, Kenya: I. Results from a community-based study

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Susanne Wiese, Lynne Elson, Felix Reichert, Barbara Mambo, Hermann Feldmeier

Background

Tungiasis is a neglected tropical disease caused by female sand fleas (Tunga penetrans) embedded in the skin. The disease is associated with important morbidity. Tungiasis is endemic along the Coast of Kenya with a prevalence ranging from 11% to 50% in school-age children. Hitherto, studies on epidemiological characteristics of tungiasis in Africa are scanty.

Methods

In a cross-sectional study 1,086 individuals from 233 households in eight villages located in Kakuyuni and Malanga Sub-locations, Kilifi County, on the Kenyan Coast, were investigated. Study participants were examined systematically and the presence and severity of tungiasis were determined using standard methods. Demographic, socio-economic, environmental and behavioral risk factors of tungiasis were assessed using a structured questionnaire. Data were analyzed using bivariate and multivariate regression analysis.

Results

The overall prevalence of tungiasis was 25.0% (95% CI 22.4–27.5%). Age-specific prevalence followed an S-shaped curve, peaking in the under-15 year old group. In 42.5% of the households at least one individual had tungiasis. 15.1% of patients were severely infected (≥ 30 lesions). In the bivariate analysis no specific animal species was identified as a risk factor for tungiasis. Multivariate analysis showed that the occurrence of tungiasis was related to living in a house with poor construction characteristics, such as mud walls (OR 3.35; 95% CI 1.71–6.58), sleeping directly on the floor (OR 1.68; 95% CI 1.03–2.74), the number of people per sleeping room (OR = 1.77; 95% CI 1.07–2.93) and washing the body without soap (OR = 7.36; 95% CI 3.08–17.62). The odds of having severe tungiasis were high in males (OR 2.29; 95% CI 1.18–44.6) and were very high when only mud puddles were available as a water source and lack of water permitted washing only once a day (OR 25.48 (95% CI 3.50–185.67) and OR 2.23 (95% CI 1.11–4.51), respectively).

Conclusions

The results of this study show that in rural Kenya characteristics of poverty determine the occurrence and the severity of tungiasis. Intra-domiciliary transmission seems to occur regularly.

Analysing published global Ebola Virus Disease research using social network analysis

PLoS Neglected Tropical Diseases News - 9 October 2017 - 9:00pm

by Christiane Hagel, Felix Weidemann, Stephan Gauch, Suzanne Edwards, Peter Tinnemann

Introduction

The 2014/2015 West African Ebola Virus Disease (EVD) outbreak attracted global attention. Numerous opinions claimed that the global response was impaired, in part because, the EVD research was neglected, although quantitative or qualitative studies did not exist. Our objective was to analyse how the EVD research landscape evolved by exploring the existing research network and its communities before and during the outbreak in West Africa.

Methods/ Principal findings

Social network analysis (SNA) was used to analyse collaborations between institutions named by co-authors as affiliations in publications on EVD. Bibliometric data of publications on EVD between 1976 and 2015 was collected from Thomson Reuters’ Web of Science Core Collection (WoS). Freely available software was used for network analysis at a global-level and for 10-year periods. The networks are presented as undirected-weighted graphs. Rankings by degree and betweenness were calculated to identify central and powerful network positions; modularity function was used to identify research communities. Overall 4,587 publications were identified, of which 2,528 were original research articles. Those yielded 1,644 authors’ affiliated institutions and 9,907 connections for co-authorship network construction. The majority of institutions were from the USA, Canada and Europe. Collaborations with research partners on the African continent did exist, but less frequently. Around six highly connected organisations in the network were identified with powerful and broker positions. Network characteristics varied widely among the 10-year periods and evolved from 30 to 1,489 institutions and 60 to 9,176 connections respectively. Most influential actors are from public or governmental institutions whereas private sector actors, in particular the pharmaceutical industry, are largely absent.

Conclusion/ Significance

Research output on EVD has increased over time and surged during the 2014/2015 outbreak. The overall EVD research network is organised around a few key actors, signalling a concentration of expertise but leaving room for increased cooperation with other institutions especially from affected countries. Finding innovative ways to maintain support for these pivotal actors while steering the global EVD research network towards an agenda driven by agreed, prioritized needs and finding ways to better integrate currently peripheral and newer expertise may accelerate the translation of research into the development of necessary live saving products for EVD ahead of the next outbreak.

Discovery by organism based high-throughput screening of new multi-stage compounds affecting <i>Schistosoma mansoni</i> viability, egg formation and production

PLoS Neglected Tropical Diseases News - 6 October 2017 - 9:00pm

by Alessandra Guidi, Cristiana Lalli, Roberto Gimmelli, Emanuela Nizi, Matteo Andreini, Nadia Gennari, Fulvio Saccoccia, Steven Harper, Alberto Bresciani, Giovina Ruberti

Schistosomiasis, one of the most prevalent neglected parasitic diseases affecting humans and animals, is caused by the Platyhelminthes of the genus Schistosoma. Schistosomes are the only trematodes to have evolved sexual dimorphism and the constant pairing with a male is essential for the sexual maturation of the female. Pairing is required for the full development of the two major female organs, ovary and vitellarium that are involved in the production of different cell types such as oocytes and vitellocytes, which represent the core elements of the whole egg machinery. Sexually mature females can produce a large number of eggs each day. Due to the importance of egg production for both life cycle and pathogenesis, there is significant interest in the search for new strategies and compounds not only affecting parasite viability but also egg production. Here we use a recently developed high-throughput organism-based approach, based on ATP quantitation in the schistosomula larval stage of Schistosoma mansoni for the screening of a large compound library, and describe a pharmacophore-based drug selection approach and phenotypic analyses to identify novel multi-stage schistosomicidal compounds. Interestingly, worm pairs treated with seven of the eight compounds identified show a phenotype characterized by defects in eggshell assemblage within the ootype and egg formation with degenerated oocytes and vitelline cells engulfment in the uterus and/or oviduct. We describe promising new molecules that not only impair the schistosomula larval stage but also impact juvenile and adult worm viability and egg formation and production in vitro.

Pathogenesis and sexual transmission of Spondweni and Zika viruses

PLoS Neglected Tropical Diseases News - 6 October 2017 - 9:00pm

by Erin M. McDonald, Nisha K. Duggal, Aaron C. Brault

The Spondweni serogroup of viruses (Flaviviridae, Flavivirus) is comprised of Spondweni virus (SPONV) and Zika virus (ZIKV), which are mosquito-borne viruses capable of eliciting human disease. Numerous cases of ZIKV sexual transmission in humans have been documented following the emergence of the Asian genotype in the Americas. The African ZIKV genotype virus was previously implicated in the first reported case of ZIKV sexual transmission. Reports of SPONV infection in humans have been associated with non-specific febrile illness, but no association with sexual transmission has been reported. In order to assess the relative efficiency of sexual transmission of different ZIKV strains and the potential capacity of SPONV to be sexually transmitted, viral loads in the male reproductive tract and in seminal fluids were assessed in interferon α/β and –γ receptor deficient (AG129) mice. Male mice were inoculated subcutaneously with Asian genotype ZIKV strains PRVABC59 (Puerto Rico, 2015), FSS13025 (Cambodia, 2010), or P6-740 (Malaysia, 1966); African genotype ZIKV strain DakAr41524 (Senegal, 1984); or SPONV strain SAAr94 (South Africa, 1955). Infectious virus was detected in 60–72% of ejaculates collected from AG129 mice inoculated with ZIKV strains. In contrast, only 4% of ejaculates from SPONV-inoculated AG129 males were found to contain infectious virus, despite viral titers in the testes that were comparable to those of ZIKV-inoculated mice. Based on these results, future studies should be undertaken to assess the role of viral genetic determinants and host tropism that dictate the differential sexual transmission potential of ZIKV and SPONV.

The <i>Babesia bovis hap2</i> gene is not required for blood stage replication, but expressed upon <i>in vitro</i> sexual stage induction

PLoS Neglected Tropical Diseases News - 6 October 2017 - 9:00pm

by Hala E. Hussein, Reginaldo G. Bastos, David A. Schneider, Wendell C. Johnson, Fatma K. Adham, William C. Davis, Jacob M. Laughery, David R. Herndon, Heba F. Alzan, Massaro W. Ueti, Carlos E. Suarez

Babesia bovis, is a tick borne apicomplexan parasite responsible for important cattle losses globally. Babesia parasites have a complex life cycle including asexual replication in the mammalian host and sexual reproduction in the tick vector. Novel control strategies aimed at limiting transmission of the parasite are needed, but transmission blocking vaccine candidates remain undefined. Expression of HAP2 has been recognized as critical for the fertilization of parasites in the Babesia-related Plasmodium, and is a leading candidate for a transmission blocking vaccine against malaria. Hereby we identified the B. bovis hap2 gene and demonstrated that it is widely conserved and differentially transcribed during development within the tick midgut, but not by blood stage parasites. The hap2 gene was disrupted by transfecting B. bovis with a plasmid containing the flanking regions of the hap2 gene and the GPF-BSD gene under the control of the ef-1α-B promoter. Comparison of in vitro growth between a hap2-KO B. bovis clonal line and its parental wild type strain showed that HAP2 is not required for the development of B. bovis in erythrocytes. However, xanthurenic acid-in vitro induction experiments of sexual stages of parasites recovered after tick transmission resulted in surface expression of HAP2 exclusively in sexual stage induced parasites. In addition, hap2-KO parasites were not able to develop such sexual stages as defined both by morphology and by expression of the B. bovis sexual marker genes 6-Cys A and B. Together, the data strongly suggests that tick midgut stage differential expression of hap2 is associated with the development of B. bovis sexual forms. Overall these studies are consistent with a role of HAP2 in tick stages of the parasite and suggest that HAP2 is a potential candidate for a transmission blocking vaccine against bovine babesiosis.

Spatial and temporal trends of visceral leishmaniasis by mesoregion in a southeastern state of Brazil, 2002-2013

PLoS Neglected Tropical Diseases News - 6 October 2017 - 9:00pm

by Thais Almeida Marques da Silva, Wendel Coura-Vital, David Soeiro Barbosa, Carla Sayuri Fogaça Oiko, Maria Helena Franco Morais, Bruna Dias Tourinho, Diogo Portella Ornelas de Melo, Ilka Afonso Reis, Mariângela Carneiro

Background

Visceral leishmaniasis (VL) is expanding in Brazil and in other South American countries, a process that has been associated with the urbanization of the disease. This study analyzes the spatial and temporal distribution of VL in the Brazilian state of Minas Gerais and identifies the areas with higher risks of transmission.

Methodology

An ecological study with spatial and time series analyzes of new confirmed cases of VL notified to the Brazilian Notifiable Disease Information System between 2002 and 2013, considering the 12 mesoregions of Minas Gerais. Two complementary methodologies were used: thematic maps of incidence and Poisson (log-linear) generalized linear model. Thematic maps using crude and smoothed cumulative incidences were generated for four trienniums. Poisson Regression measured the variation of the average number of cases from one year to the following, for each mesoregion.

Principal findings

The 5,778 cases analyzed revealed a heterogeneous spatial and temporal distribution of VL in Minas Gerais. Six mesoregions (Central Mineira, Jequitinhonha, Metropolitan area of Belo Horizonte, Northwest of Minas, North of Minas, and Vale do Rio Doce) were responsible for the expansion and maintenance of VL, with incidence rates as high as 26/100,000 inhabitants. The Vale do Rio Doce and Jequitinhonha mesoregions showed a considerable increase in the incidence rates in the last period studied. The other six mesoregions reported only sporadic cases and presented low and unsteady incidence rates, reaching a maximum of 1.2/100,000 inhabitants.

Conclusions/Significance

The results contribute to further the current understanding about the expansion of VL in Minas Gerais and may help guide actions for disease control.

Lymphatic filariasis transmission on Mafia Islands, Tanzania: Evidence from xenomonitoring in mosquito vectors

PLoS Neglected Tropical Diseases News - 6 October 2017 - 9:00pm

by Yahya A. Derua, Susan F. Rumisha, Bernard M. Batengana, Demetrius A. Max, Grades Stanley, William N. Kisinza, Leonard E. G. Mboera

Introduction

Lymphatic filariasis (LF) is a chronic nematode infection transmitted by mosquitoes and in sub-Saharan Africa it is caused by Wuchereria bancrofti. The disease was targeted for global elimination by 2020 using repeated community-wide mass drug administration (MDA) distributed in endemic areas. However, recently, there has been a growing recognition of the potential role of including vector control as a supplement to MDA to achieve elimination goal. This study was carried out to determine mosquito abundance and transmission of bancroftian filariasis on Mafia Islands in Tanzania as a prerequisite for a search for appropriate vector control methods to complement the ongoing MDA campaign.

Methods

Mosquitoes were collected indoor and outdoor using Centre for Disease Control (CDC) light and gravid traps, respectively. Collected mosquitoes were identified based on their differential morphological features and Anopheles gambiae complex and An. funestus group were further identified to their respective sibling species by polymerase chain reaction (PCR). Filarial mosquito vectors were then examined for infection with Wuchereria bancrofti by microscopy and PCR technique.

Results

Overall, a total of 35,534 filarial mosquito vectors were collected, of which Anopheles gambiae complex, An. funestus group and Culex quinquefasciatus Say accounted for 1.3, 0.5 and 98.2%, respectively. Based on PCR identification, An. gambiae sensu stricto (s.s) and An. funestus s.s sibling species accounted for 88.3% and 99.1% of the identified members of the An. gambiae complex and An. funestus group, respectively. A total of 7,936 mosquitoes were examined for infection with W. bancrofti by microscopy. The infection and infectivity rates were 0.25% and 0.08%, respectively. Using pool screen PCR technique, analysis of 324 mosquito pools (each with 25 mosquitoes) resulted to an estimated infection rate of 1.7%.

Conclusion

The study has shown that Cx. quinquefasciatus is the dominant mosquito on Mafia Islands. By using mosquito infectivity as proxy to human infection, the study indicates that W. bancrofti transmission is still ongoing on Mafia Islands after more than a decade of control activities based on MDA.

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