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Environmental enteric dysfunction pathways and child stunting: A systematic review

PLoS Neglected Tropical Diseases News - 19 January 2018 - 10:00pm

by Kaitlyn M. Harper, Maxine Mutasa, Andrew J. Prendergast, Jean Humphrey, Amee R. Manges


Environmental enteric dysfunction (EED) is commonly defined as an acquired subclinical disorder of the small intestine, characterized by villous atrophy and crypt hyperplasia. EED has been proposed to underlie stunted growth among children in developing countries. A collection of biomarkers, organized into distinct domains, has been used to measure different aspects of EED. Here, we examine whether these hypothesized relationships, among EED domains and between each domain and stunting, are supported by data from recent studies.


A systematic literature search was conducted using PubMed, MEDLINE, EMBASE, Web of Science, and CINAHL between January 1, 2010 and April 20, 2017. Information on study objective, design, population, location, biomarkers, and results were recorded, as well as qualitative and quantitative definitions of EED. Biomarkers were organized into five EED domains, and the number of studies that support or do not support relationships among domains and between each domain with stunting were summarized.


There was little evidence to support the pathway from intestinal permeability to microbial translocation and from microbial translocation to stunting, but stronger support existed for the link between intestinal inflammation and systemic inflammation and for intestinal inflammation and stunting. There was conflicting evidence for the pathways from intestinal damage to intestinal permeability and intestinal damage to stunting.


These results suggest that certain EED biomarkers may require reconsideration, particularly those most difficult to measure, such as microbial translocation and intestinal permeability. We discuss several issues with currently used biomarkers and recommend further analysis of pathogen-induced changes to the intestinal microbiota as a pathway leading to stunting.

Understanding the legal trade of cattle and camels and the derived risk of Rift Valley Fever introduction into and transmission within Egypt

PLoS Neglected Tropical Diseases News - 19 January 2018 - 10:00pm

by Sebastian Napp, Veronique Chevalier, Núria Busquets, Paolo Calistri, Jordi Casal, Mohamed Attia, Rehab Elbassal, Heba Hosni, Hatem Farrag, Noura Hassan, Rasha Tawfik, Sohair Abd Elkader, Shahin Bayomy

Rift Valley Fever (RVF) is a mosquito-borne zoonosis, which may cause significant losses for the livestock sector and have serious public health implications. Egypt has been repeatedly affected by RVF epidemics, mainly associated to the importation of animals from sub-Saharan countries, where the disease is endemic. The objective of our study was the improvement of the surveillance and control strategies implemented in Egypt. In order to do that, first we evaluated the legal trade of live animals into and within Egypt. Then, we assessed the risk of Rift Valley Fever virus (RVFV) transmission within the country using a multi-criteria evaluation approach. Finally, we combined the animal trade and the risk of RVFV transmission data to identify those areas and periods in which the introduction of RVFV is more likely. Our results indicate that the main risk of RVFV introduction is posed by the continuous flow of large number of camels coming from Sudan. The risk of RVFV transmission by vectors is restricted to the areas surrounding the Nile river, and does not vary significantly throughout the year. Imported camels are taken to quarantines, where the risk of RVFV transmission by vectors is generally low. Then, they are taken to animal markets or slaughterhouses, many located in populated areas, where the risk of RVFV transmission to animals or humans is much higher. The measures currently implemented (quarantines, vaccination or testing) seem to have a limited effect in reducing the risk of RVFV introduction, and therefore other (risk-based) surveillance strategies are proposed.

Seasonally timed treatment programs for <i>Ascaris lumbricoides</i> to increase impact—An investigation using mathematical models

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Emma L. Davis, Leon Danon, Joaquín M. Prada, Sharmini A. Gunawardena, James E. Truscott, Johnny Vlaminck, Roy M. Anderson, Bruno Levecke, Eric R Morgan, T. Deirdre Hollingsworth

There is clear empirical evidence that environmental conditions can influence Ascaris spp. free-living stage development and host reinfection, but the impact of these differences on human infections, and interventions to control them, is variable. A new model framework reflecting four key stages of the A. lumbricoides life cycle, incorporating the effects of rainfall and temperature, is used to describe the level of infection in the human population alongside the environmental egg dynamics. Using data from South Korea and Nigeria, we conclude that settings with extreme fluctuations in rainfall or temperature could exhibit strong seasonal transmission patterns that may be partially masked by the longevity of A. lumbricoides infections in hosts; we go on to demonstrate how seasonally timed mass drug administration (MDA) could impact the outcomes of control strategies. For the South Korean setting the results predict a comparative decrease of 74.5% in mean worm days (the number of days the average individual spend infected with worms across a 12 month period) between the best and worst MDA timings after four years of annual treatment. The model found no significant seasonal effect on MDA in the Nigerian setting due to a narrower annual temperature range and no rainfall dependence. Our results suggest that seasonal variation in egg survival and maturation could be exploited to maximise the impact of MDA in certain settings.

Inferring the risk factors behind the geographical spread and transmission of Zika in the Americas

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Lauren M. Gardner, András Bóta, Karthik Gangavarapu, Moritz U. G. Kraemer, Nathan D. Grubaugh


An unprecedented Zika virus epidemic occurred in the Americas during 2015-2016. The size of the epidemic in conjunction with newly recognized health risks associated with the virus attracted significant attention across the research community. Our study complements several recent studies which have mapped epidemiological elements of Zika, by introducing a newly proposed methodology to simultaneously estimate the contribution of various risk factors for geographic spread resulting in local transmission and to compute the risk of spread (or re-introductions) between each pair of regions. The focus of our analysis is on the Americas, where the set of regions includes all countries, overseas territories, and the states of the US.

Methodology/Principal findings

We present a novel application of the Generalized Inverse Infection Model (GIIM). The GIIM model uses real observations from the outbreak and seeks to estimate the risk factors driving transmission. The observations are derived from the dates of reported local transmission of Zika virus in each region, the network structure is defined by the passenger air travel movements between all pairs of regions, and the risk factors considered include regional socioeconomic factors, vector habitat suitability, travel volumes, and epidemiological data. The GIIM relies on a multi-agent based optimization method to estimate the parameters, and utilizes a data driven stochastic-dynamic epidemic model for evaluation. As expected, we found that mosquito abundance, incidence rate at the origin region, and human population density are risk factors for Zika virus transmission and spread. Surprisingly, air passenger volume was less impactful, and the most significant factor was (a negative relationship with) the regional gross domestic product (GDP) per capita.


Our model generates country level exportation and importation risk profiles over the course of the epidemic and provides quantitative estimates for the likelihood of introduced Zika virus resulting in local transmission, between all origin-destination travel pairs in the Americas. Our findings indicate that local vector control, rather than travel restrictions, will be more effective at reducing the risks of Zika virus transmission and establishment. Moreover, the inverse relationship between Zika virus transmission and GDP suggests that Zika cases are more likely to occur in regions where people cannot afford to protect themselves from mosquitoes. The modeling framework is not specific for Zika virus, and could easily be employed for other vector-borne pathogens with sufficient epidemiological and entomological data.

Assessing the feasibility of interrupting the transmission of soil-transmitted helminths through mass drug administration: The DeWorm3 cluster randomized trial protocol

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Kristjana Hrönn Ásbjörnsdóttir, Sitara S. Rao Ajjampur, Roy M. Anderson, Robin Bailey, Iain Gardiner, Katherine E. Halliday, Moudachirou Ibikounle, Khumbo Kalua, Gagandeep Kang, D. Timothy J. Littlewood, Adrian J. F. Luty, Arianna Rubin Means, William Oswald, Rachel L. Pullan, Rajiv Sarkar, Fabian Schär, Adam Szpiro, James E. Truscott, Marleen Werkman, Elodie Yard, Judd L. Walson, The DeWorm3 Trials Team

Trial registration NCT03014167

Identification of novel leishmanicidal molecules by virtual and biochemical screenings targeting <i>Leishmania</i> eukaryotic initiation factor 4A

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Emna Harigua-Souiai, Yosser Zina Abdelkrim, Imen Bassoumi-Jamoussi, Ons Zakraoui, Guillaume Bouvier, Khadija Essafi-Benkhadir, Josette Banroques, Nathan Desdouits, Hélène Munier-Lehmann, Mourad Barhoumi, N. Kyle Tanner, Michael Nilges, Arnaud Blondel, Ikram Guizani

Leishmaniases are neglected parasitic diseases in spite of the major burden they inflict on public health. The identification of novel drugs and targets constitutes a research priority. For that purpose we used Leishmania infantum initiation factor 4A (LieIF), an essential translation initiation factor that belongs to the DEAD-box proteins family, as a potential drug target. We modeled its structure and identified two potential binding sites. A virtual screening of a diverse chemical library was performed for both sites. The results were analyzed with an in-house version of the Self-Organizing Maps algorithm combined with multiple filters, which led to the selection of 305 molecules. Effects of these molecules on the ATPase activity of LieIF permitted the identification of a promising hit (208) having a half maximal inhibitory concentration (IC50) of 150 ± 15 μM for 1 μM of protein. Ten chemical analogues of compound 208 were identified and two additional inhibitors were selected (20 and 48). These compounds inhibited the mammalian eIF4I with IC50 values within the same range. All three hits affected the viability of the extra-cellular form of L. infantum parasites with IC50 values at low micromolar concentrations. These molecules showed non-significant toxicity toward THP-1 macrophages. Furthermore, their anti-leishmanial activity was validated with experimental assays on L. infantum intramacrophage amastigotes showing IC50 values lower than 4.2 μM. Selected compounds exhibited selectivity indexes between 19 to 38, which reflects their potential as promising anti-Leishmania molecules.

Geographical distribution of soil transmitted helminths and the effects of community type in South Asia and South East Asia – A systematic review

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Zachary A. Silver, Saravanakumar P. Kaliappan, Prasanna Samuel, Srinivasan Venugopal, Gagandeep Kang, Rajiv Sarkar, Sitara S. R. Ajjampur


Soil-transmitted helminth (STH) infections are among the most prevalent neglected tropical diseases (NTD) worldwide. Since the publication of the WHO road map to combat NTD in 2012, there has been a renewed commitment to control STH. In this study, we analysed the geographical distribution and effect of community type on prevalence of hookworm, Trichuris and Ascaris in south Asia and south east Asia.


We conducted a systematic review of open-access literature published in PubMed Central and the Global Atlas of Helminth Infection. A total of 4182 articles were available and after applying selection criteria, 174 studies from the region were retained for analysis.

Principal findings

Ascaris was the commonest STH identified with an overall prevalence of 18% (95% CI, 14–23%) followed by Trichuris (14%, 9–19%) and hookworm (12%, 9–15%). Hookworm prevalence was highest in Laos, Vietnam and Cambodia. We found a geographical overlap in countries with high prevalence rates for Trichuris and Ascaris (Malaysia, Philippines, Myanmar, Vietnam and Bangladesh). When the effect of community type was examined, prevalence rates of hookworm was comparable in rural (19%, 14–24%) and tribal communities (14%, 10–19%). Tribal communities, however, showed higher prevalence of Trichuris (38%, 18–63%) and Ascaris (32%, 23–43%) than rural communities (13%, 9–20% and 14%, 9–20% respectively). Considerable between and within country heterogeneity in the distribution of STH (I2 >90%) was also noted. When available data from school aged children (SAC) were analysed, prevalence of Ascaris (25% 16–31%) and Trichuris (22%, 14–34%) were higher than among the general population while that of hookworm (10%, 7–16%) was comparable.


Our analysis showed significant variation in prevalence rates between and within countries in the region. Highlighting the importance of community type in prevalence and species mix, we showed that tribal and rural communities had higher hookworm infections than urban communities and for ascariasis and trichuriasis, tribal populations had higher levels of infection than rural populations. We also found a higher prevalence of ascariasis and trichuriasis in SAC compared to the general population but comparable levels of hookworm infections. These key findings need to be taken into account in planning future MDA and other interventions.

Genetic diversity and potential routes of transmission of <i>Mycobacterium bovis</i> in Mozambique

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Adelina Machado, Teresa Rito, Solomon Ghebremichael, Nuelma Muhate, Gabriel Maxhuza, Custodia Macuamule, Ivania Moiane, Baltazar Macucule, Angelica Suzana Marranangumbe, Jorge Baptista, Joaquim Manguele, Tuija Koivula, Elizabeth Maria Streicher, Robin Mark Warren, Gunilla Kallenius, Paul van Helden, Margarida Correia-Neves

Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa, with risk factors such as HIV and direct contact with animals or consumption of Mycobacterium bovis infected animal products. In order to understand and quantify this risk and design intervention strategies, good epidemiological studies are needed. Such studies can include molecular typing of M. bovis isolates. The aim of this study was to apply these tools to provide novel information concerning the distribution of bovine tuberculosis in cattle in Mozambique and thereby provide relevant information to guide policy development and strategies to contain the disease in livestock, and reduce the risk associated with transmission to humans. A collection of 178 M. bovis isolates was obtained from cattle in Mozambique. Using spoligotyping and regions of difference analysis, we classified the isolates into clonal complexes, thus reporting the first characterisation of M. bovis strains in this region. Data from MIRU-VNTR typing was used to compare isolates from a number of African countries, revealing a deeply geographically structured diversity of M. bovis. Eastern Africa appears to show high diversity, suggesting deep evolution in that region. The diversity of M. bovis in Africa does not seem to be a function of recent importation of animals, but is probably maintained within each particular region by constant reinfection from reservoir animals. Understanding the transmission routes of M. bovis in Mozambique and elsewhere is essential in order to focus public health and veterinary resources to contain bovine tuberculosis.

A comparative analysis of preservation techniques for the optimal molecular detection of hookworm DNA in a human fecal specimen

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Marina Papaiakovou, Nils Pilotte, Ben Baumer, Jessica Grant, Kristjana Asbjornsdottir, Fabian Schaer, Yan Hu, Raffi Aroian, Judd Walson, Steven A. Williams


Proper collection and storage of fecal samples is necessary to guarantee the subsequent reliability of DNA-based soil-transmitted helminth diagnostic procedures. Previous research has examined various methods to preserve fecal samples for subsequent microscopic analysis or for subsequent determination of overall DNA yields obtained following DNA extraction. However, only limited research has focused on the preservation of soil-transmitted helminth DNA in stool samples stored at ambient temperature or maintained in a cold chain for extended periods of time.


Quantitative real-time PCR was used in this study as a measure of the effectiveness of seven commercially available products to preserve hookworm DNA over time and at different temperatures. Results were compared against “no preservative” controls and the “gold standard” of rapidly freezing samples at -20°C. The preservation methods were compared at both 4°C and at simulated tropical ambient temperature (32°C) over a period of 60 days. Evaluation of the effectiveness of each preservative was based on quantitative real-time PCR detection of target hookworm DNA.


At 4°C there were no significant differences in DNA amplification efficiency (as measured by Cq values) regardless of the preservation method utilized over the 60-day period. At 32°C, preservation with FTA cards, potassium dichromate, and a silica bead two-step desiccation process proved most advantageous for minimizing Cq value increases, while RNA later, 95% ethanol and Paxgene also demonstrate some protective effect. These results suggest that fecal samples spiked with known concentrations of hookworm-derived egg material can remain at 4°C for 60 days in the absence of preservative, without significant degradation of the DNA target. Likewise, a variety of preservation methods can provide a measure of protection in the absence of a cold chain. As a result, other factors, such as preservative toxicity, inhibitor resistance, preservative cost, shipping requirements, sample infectivity, and labor costs should be considered when deciding upon an appropriate method for the storage of fecal specimens for subsequent PCR analysis. Balancing logistical factors and the need to preserve the target DNA, we believe that under most circumstances 95% ethanol provides the most pragmatic choice for preserving stool samples in the field.

Testing for soil-transmitted helminth transmission elimination: Analysing the impact of the sensitivity of different diagnostic tools

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Marleen Werkman, James E. Wright, James E. Truscott, Alice V. Easton, Rita G. Oliveira, Jaspreet Toor, Alison Ower, Kristjana H. Ásbjörnsdóttir, Arianna R. Means, Sam H. Farrell, Judd L. Walson, Roy M. Anderson

In recent years, an increased focus has been placed upon the possibility of the elimination of soil-transmitted helminth (STH) transmission using various interventions including mass drug administration. The primary diagnostic tool recommended by the WHO is the detection of STH eggs in stool using the Kato-Katz (KK) method. However, detecting infected individuals using this method becomes increasingly difficult as the intensity of infection decreases. Newer techniques, such as qPCR, have been shown to have greater sensitivity than KK, especially at low prevalence. However, the impact of using qPCR on elimination thresholds is yet to be investigated. In this paper, we aim to quantify how the sensitivity of these two diagnostic tools affects the optimal prevalence threshold at which to declare the interruption of transmission with a defined level of confidence. A stochastic, individual-based STH transmission model was used in this study to simulate the transmission dynamics of Ascaris and hookworm. Data from a Kenyan deworming study were used to parameterize the diagnostic model which was based on egg detection probabilities. The positive and negative predictive values (PPV and NPV) were calculated to assess the quality of any given threshold, with the optimal threshold value taken to be that at which both were maximised. The threshold prevalence of infection values for declaring elimination of Ascaris transmission were 6% and 12% for KK and qPCR respectively. For hookworm, these threshold values are lower at 0.5% and 2% respectively. Diagnostic tests with greater sensitivity are becoming increasingly important as we approach the elimination of STH transmission in some regions of the world. For declaring the elimination of transmission, using qPCR to diagnose STH infection results in the definition of a higher prevalence, than when KK is used.

Histoplasmosis in Africa: An emerging or a neglected disease?

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Rita O. Oladele, Olusola O. Ayanlowo, Malcolm D. Richardson, David W. Denning

Histoplasmosis in Africa has markedly increased since the advent of the HIV/AIDS epidemic but is under-recognised. Pulmonary histoplasmosis may be misdiagnosed as tuberculosis (TB). In the last six decades (1952–2017), 470 cases of histoplasmosis have been reported. HIV-infected patients accounted for 38% (178) of the cases. West Africa had the highest number of recorded cases with 179; the majority (162 cases) were caused by Histoplasma capsulatum var. dubuosii (Hcd). From the Southern African region, 150 cases have been reported, and the majority (119) were caused by H. capsulatum var. capsulatum (Hcc). There have been 12 histoplasmin skin test surveys with rates of 0% to 35% positivity. Most cases of Hcd presented as localised lesions in immunocompetent persons; however, it was disseminated in AIDS patients. Rapid diagnosis of histoplasmosis in Africa is only currently possible using microscopy; antigen testing and PCR are not available in most of Africa. Treatment requires amphotericin B and itraconazole, both of which are not licensed or available in several parts of Africa.

Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Jose Muñoz, Maria Rosa Ballester, Rosa Maria Antonijoan, Ignasi Gich, Montse Rodríguez, Enrico Colli, Silvia Gold, Alejandro J. Krolewiecki

Trial registration NCT03173742.

Evaluating the sustainability, scalability, and replicability of an STH transmission interruption intervention: The DeWorm3 implementation science protocol

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Arianna Rubin Means, Sitara S. R. Ajjampur, Robin Bailey, Katya Galactionova, Marie-Claire Gwayi-Chore, Katherine Halliday, Moudachirou Ibikounle, Sanjay Juvekar, Khumbo Kalua, Gagandeep Kang, Pallavi Lele, Adrian J. F. Luty, Rachel Pullan, Rajiv Sarkar, Fabian Schär, Fabrizio Tediosi, Bryan J. Weiner, Elodie Yard, Judd Walson, on behalf of the DeWorm3 Implementation Science Team

Hybrid trials that include both clinical and implementation science outcomes are increasingly relevant for public health researchers that aim to rapidly translate study findings into evidence-based practice. The DeWorm3 Project is a series of hybrid trials testing the feasibility of interrupting the transmission of soil transmitted helminths (STH), while conducting implementation science research that contextualizes clinical research findings and provides guidance on opportunities to optimize delivery of STH interventions. The purpose of DeWorm3 implementation science studies is to ensure rapid and efficient translation of evidence into practice. DeWorm3 will use stakeholder mapping to identify individuals who influence or are influenced by school-based or community-wide mass drug administration (MDA) for STH and to evaluate network dynamics that may affect study outcomes and future policy development. Individual interviews and focus groups will generate the qualitative data needed to identify factors that shape, contextualize, and explain DeWorm3 trial outputs and outcomes. Structural readiness surveys will be used to evaluate the factors that drive health system readiness to implement novel interventions, such as community-wide MDA for STH, in order to target change management activities and identify opportunities for sustaining or scaling the intervention. Process mapping will be used to understand what aspects of the intervention are adaptable across heterogeneous implementation settings and to identify contextually-relevant modifiable bottlenecks that may be addressed to improve the intervention delivery process and to achieve intervention outputs. Lastly, intervention costs and incremental cost-effectiveness will be evaluated to compare the efficiency of community-wide MDA to standard-of-care targeted MDA both over the duration of the trial and over a longer elimination time horizon.

Combined effectiveness of anthelmintic chemotherapy and WASH among HIV-infected adults

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Arianna R. Means, Lisette van Lieshout, Eric Brienen, Krista Yuhas, James P. Hughes, Paul Ndungu, Benson Singa, Judd L. Walson


Current global helminth control guidelines focus on regular deworming of targeted populations for morbidity control. However, water, sanitation, and hygiene (WASH) interventions may also be important for reducing helminth transmission. We evaluated the impact of different potential helminth protective packages on infection prevalence, including repeated treatment with albendazole and praziquantel with and without WASH access.

Methodology/Principal findings

We conducted a cohort study nested within a randomized trial of empiric deworming of HIV-infected adults in Kenya. Helminth infections and infection intensity were diagnosed using semi-quantitative real-time PCR. We conducted a manual forward stepwise model building approach to identify if there are packages of interventions that may be protective against an STH infection of any species (combined outcome) and each helminth species individually. We conducted secondary analyses using the same approach only amongst individuals with no anthelmintis exposure. We used interaction terms to test for potential intervention synergy. Approximately 22% of the 701 stool samples provided were helminth-infected, most of which were of low to moderate intensity. The odds of infection with any STH species were lower for individuals who were treated with albendazole (aOR:0.11, 95%CI: 0.05, 0.20, p<0.001), adjusting for age and sex. Although most WASH conditions demonstrated minimal additional benefit in reducing the probability of infection with any STH species, access to safe flooring did appear to offer some additional protection (aOR:0.34, 95%CI: 0.20, 0.56, p<0.001). For schistosomiasis, only treatment with praziquantel was protective (aOR:0.30 95%CI: 0.14, 0.60, p = 0.001). Amongst individuals who were not treated with albendazole or praziquantel, the most protective intervention package to reduce probability of STH infections included safe flooring (aOR:0.34, 95%CI: 0.20, 0.59, p<0.001) and latrine access (aOR:0.59, 95%CI: 0.35, 0.99, p = 0.05). Across all species, there was no evidence of synergy or antagonism between anthelmintic chemotherapy with albendazole or praziquantel and WASH resources.


Deworming is effective in reducing the probability of helminth infections amongst HIV-infected adults. With the exception of safe flooring, WASH offers minimal additional benefit. However, WASH does appear to significantly reduce infection prevalence in adults who are not treated with chemotherapy.

Trial registration, NCT00507221.

Assessment of serum pharmacokinetics and urinary excretion of albendazole and its metabolites in human volunteers

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Laura Ceballos, Alejandro Krolewiecki, Marisa Juárez, Laura Moreno, Fabian Schaer, Luis I. Alvarez, Rubén Cimino, Judd Walson, Carlos E. Lanusse


Soil Transmitted Helminth (STH) infections negatively impact physical and mental development in human populations. Current WHO guidelines recommend morbidity control of these infections through mass drug administration (MDA) using albendazole (ABZ) or mebendazole. Despite major reductions in STH associated morbidity globally, not all programs have demonstrated the expected impact on prevalence of parasite infections. These therapeutic failures may be related to poor programmatic coverage, suboptimal adherence or the exposure of parasites to sub-therapeutic drug concentrations. As part of the DeWorm3 project, we sought to characterize the serum disposition kinetics and pattern of urinary excretion of ABZ and its main metabolites ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO2) in humans, and the assessment of the duration and optimal time point where ABZ and/or its metabolites can be measured in urine as an indirect assessment of an individual’s adherence to treatment.

Methodology/Principal findings

Consecutive venous blood and urine samples were collected from eight (8) human volunteers up to 72 h post-ABZ oral administration. ABZ/metabolites were quantified by HPLC. The ABZSO metabolite was the main analyte recovered both in serum and urine. ABZSO Cmax in serum was 1.20 ± 0.44 μg/mL, reached at 4.75 h post-treatment. In urine, ABZSO Cmax was 3.24 ± 1.51 μg/mL reached at 6.50 h post-ABZ administration.


Pharmacokinetic data obtained for ABZ metabolites in serum and urine, including the recovery of the ABZ sulphoxide derivative up to 72 h in both matrixes and the recovery of the amino-ABZ sulphone metabolite in urine samples, are suggesting the possibility of developing a urine based method to assess compliance to ABZ treatment. Such an assay may be useful to optimize ABZ use in human patients.

Trial registration NCT03192449.

The rise of neglected tropical diseases in the "new Texas"

PLoS Neglected Tropical Diseases News - 18 January 2018 - 10:00pm

by Peter J. Hotez

Within the last five years, the State of Texas has experienced either transmission or outbreaks of Ebola, chikungunya, West Nile, and Zika virus infections. Autochthonous transmission of neglected parasitic and bacterial diseases has also become increasingly reported. The rise of such emerging and neglected tropical diseases (NTDs) has not occurred by accident but instead reflects rapidly evolving changes and shifts in a “new” Texas beset by modern and globalizing forces that include rapid expansions in population together with urbanization and human migrations, altered transportation patterns, climate change, steeply declining vaccination rates, and a new paradigm of poverty known as “blue marble health.” Summarized here are the major NTDs now affecting Texas. In addition to the vector-borne viral diseases highlighted above, there also is a high level of parasitic infections, including Chagas disease, trichomoniasis, and possibly leishmaniasis and toxocariasis, as well as typhus-group rickettsiosis, a vector-borne bacterial infection. I also highlight some of the key shifts in emerging and neglected disease patterns, partly due to an altered and evolving economic and ecological landscape in the new Texas, and provide some preliminary disease burden estimates for the major prevalent and incident NTDs.

Occupational exposure to human <i>Mycobacterium bovis</i> infection: A systematic review

PLoS Neglected Tropical Diseases News - 16 January 2018 - 10:00pm

by Flora Vayr, Guillaume Martin-Blondel, Frederic Savall, Jean-Marc Soulat, Gaëtan Deffontaines, Fabrice Herin


Mycobacterium bovis (M. bovis) is the main causative agent of bovine zoonotic tuberculosis. The aim of this systematic review is to highlight the occupational exposure to bovine tuberculosis due to M. bovis.

Methodology/principal findings

A computer based literature search was carried out to identify papers published between January 2006 and March 2017. “PubMed, Cochrane Library and Science Direct” databases were searched systematically. Articles presenting the following properties were included: (i) focusing on M. bovis; (ii) concerning occupational exposure to bovine tuberculosis. A quality assessment was performed after selection of studies. Our search strategy identified a total of 3,264 papers of which 29 studies met the inclusion criteria. Of the 29 articles, 17 were cross-sectional studies (6 were of high quality and scored in the range of 6–7, 11 were of moderate quality and scored in the range 3–5), 10 were case reports, and 2 were reviews. Different occupational fields exposing to the disease were described: livestock sector, particularly in contact with dairy cattle (farmers, veterinaries and assistants, abattoir workers) and working in contact with wildlife (hunters, taxidermists).


A specific guideline for occupational practitioners taking care of employees exposed to bovine tuberculosis is warranted and should be tailored to level of exposure. This review was intended to be the first step of such a project. Articles were identified from various continents and countries with different socio-economic situations, broadening our understanding of the worldwide situation. Published data on occupational exposure in developed countries are scarce. We had to extrapolate findings from countries with higher prevalence of the disease.

L-arginine supplementation reduces mortality and improves disease outcome in mice infected with <i>Trypanosoma cruzi</i>

PLoS Neglected Tropical Diseases News - 16 January 2018 - 10:00pm

by Sofía Carbajosa, Héctor O. Rodríguez-Angulo, Susana Gea, Carlos Chillón-Marinas, Cristina Poveda, María C. Maza, Diana Colombet, Manuel Fresno, Núria Gironès

Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America, recently emerging on other continents due to migration. As infection in mice is characterized by depletion of plasma L-arginine, the effect on infection outcome was tested in mice with or without L-arginine supplementation and treatment with 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and citrulline were reduced in the heart and plasma of infected mice, whereas levels of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher. Moreover, L-arginine supplementation decreased parasitemia and heart parasite burden, improving clinical score and survival. Nitric oxide production in heart tissue and plasma was increased by L-arginine supplementation, while pharmacological inhibition of iNOS yielded an increase in parasitemia and worse clinical score. Interestingly, electrocardiograms improved in mice supplemented with L-arginine, suggesting that it modulates infection and heart function and is thus a potential biomarker of pathology. More importantly, L-arginine may be useful for treating T. cruzi infection, either alone or in combination with other antiparasitic drugs.

Modelling the large-scale yellow fever outbreak in Luanda, Angola, and the impact of vaccination

PLoS Neglected Tropical Diseases News - 16 January 2018 - 10:00pm

by Shi Zhao, Lewi Stone, Daozhou Gao, Daihai He


Yellow fever (YF), transmitted via bites of infected mosquitoes, is a life-threatening viral disease endemic to tropical and subtropical regions of Africa and South America. YF has largely been controlled by widespread national vaccination campaigns. Nevertheless, between December 2015 and August 2016, YF resurged in Angola, quickly spread and becoming the largest YF outbreak for the last 30 years. Recently, YF resurged again in Brazil (December 2016). Thus, there is an urgent need to gain better understanding of the transmission pattern of YF.


The present study provides a refined mathematical model, combined with modern likelihood-based statistical inference techniques, to assess and reconstruct important epidemiological processes underlying Angola’s YF outbreak. This includes the outbreak’s attack rate, the reproduction number (R 0), the role of the mosquito vector, the influence of climatic factors and the unusual but noticeable appearance of two-waves in the YF outbreak. The model explores actual and hypothetical vaccination strategies, and the impacts of possible human reactive behaviors (e.g., response to media precautions).


While there were 73 deaths reported over the study period, the model indicates that the vaccination campaign saved 5.1-fold more people from death and saved from illness 5.6-fold of the observed 941 cases. Delaying the availability of the vaccines further would have greatly worsened the epidemic in terms of increased case numbers and mortality. The analysis estimated a mean R 0 ≈ 2 . 6 - 3 . 4 and an estimated YF attack rate of 0.09-0.15% (proportion of population infected by YFV) over the whole period from December 2015 to August 2016. Our estimated lower and upper bounds of R 0 are in line with previous studies. Unusually, R 0 oscillated in a manner that was “delayed” with the reported deaths. High recent number of deaths were associated (followed) with periods of relatively low disease transmission and low R 0, and vice-versa. The time-series of Luanda’s YF cases suggest the outbreak occurred in two waves, a feature that would have become far more prominent had there been no mass vaccination. The waves could possibly be due to protective reactive behavioral changes of the population affecting the mosquito population. The second wave could well be an outcome of the March-April rainfall patterns in the 2016 El Niño year by creating ideal conditions for the breeding of the mosquito vectors. The modelling framework is a powerful tool for studying future YF epidemic outbreaks, and provides a basis for future vaccination campaign evaluations.

Isolation and complete genome analysis of neurotropic dengue virus serotype 3 from the cerebrospinal fluid of an encephalitis patient

PLoS Neglected Tropical Diseases News - 12 January 2018 - 10:00pm

by Rama Dhenni, Mulya Rahma Karyanti, Nina Dwi Putri, Benediktus Yohan, Frilasita A. Yudhaputri, Chairin Nisa Ma'roef, Araniy Fadhilah, Aditya Perkasa, Restuadi Restuadi, Hidayat Trimarsanto, Irawan Mangunatmadja, Jeremy P. Ledermann, Ronald Rosenberg, Ann M. Powers, Khin Saw Aye Myint, R. Tedjo Sasmono

Although neurological manifestations associated with dengue viruses (DENV) infection have been reported, there is very limited information on the genetic characteristics of neurotropic DENV. Here we describe the isolation and complete genome analysis of DENV serotype 3 (DENV-3) from cerebrospinal fluid of an encephalitis paediatric patient in Jakarta, Indonesia. Next-generation sequencing was employed to deduce the complete genome of the neurotropic DENV-3 isolate. Based on complete genome analysis, two unique and nine uncommon amino acid changes in the protein coding region were observed in the virus. A phylogenetic tree and molecular clock analysis revealed that the neurotropic virus was a member of Sumatran-Javan clade of DENV-3 genotype I and shared a common ancestor with other isolates from Jakarta around 1998. This is the first report of neurotropic DENV-3 complete genome analysis, providing detailed information on the genetic characteristics of this virus.