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Neurogenic mediators contribute to local edema induced by <i>Micrurus lemniscatus</i> venom

PLoS Neglected Tropical Diseases News - 21 November 2017 - 10:00pm

by Luciana Lyra Casais-e-Silva, Catarina Teixeira

Background/Aims

Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV) to induce local edema. We also explored mechanisms underlying this effect, focussing on participation of neuropeptides and mast cells.

Methodology/Principal findings

Intraplantar injection of MLV (1–10μg/paw) in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs). MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min) of rats with either prometazine, a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively) markedly reduced MLV-induced edema.

Conclusions/Significance

In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms.

Poverty and health among CDC plantation labourers in Cameroon: Perceptions, challenges and coping strategies

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Valerie Makoge, Lenneke Vaandrager, Harro Maat, Maria Koelen

Creating better access to good quality healthcare for the poor is a major challenge to development. In this study, we examined inter-linkages between poverty and disease, referred to as poverty-related diseases (PRDs), by investigating how Cameroon Development Corporation (CDC) camp dwellers respond to diseases that adversely affect their health and wellbeing. Living in plantation camps is associated with poverty, overcrowding, poor sanitation and the rapid spread of diseases. In a survey of 237 CDC camp dwellers in Cameroon, we used the health belief model to understand the drivers (perceived threats, benefits and cues for treatment seeking) of reported responses. Using logistic regression analysis, we looked for trends in people’s response to malaria. We calculated the odds ratio of factors shown to have an influence on people’s health, such as food, water, sanitation challenges and seeking formal healthcare for malaria. Malaria (40.3%), cholera (20.8%) and diarrhoea (17.7%) were the major PRDs perceived by camp dwellers. We found a strong link between what respondents perceived as PRDS and hygiene conditions. Poverty for our respondents was more about living in poor hygiene conditions than lack of money. Respondents perceived health challenges as stemming from their immediate living environment. Moreover, people employed self-medication and other informal health practices to seek healthcare. Interestingly, even though respondents reported using formal healthcare services as a general response to illness (84%), almost 90% stated that, in the case of malaria, they would use informal healthcare services. Our study recommends that efforts to curb the devastating effects of PRDs should have a strong focus on perceptions (i.e. include diseases that people living in conditions of poverty perceive as PRDs) and on hygiene practices, emphasising how they can be improved. By providing insights into the inter-linkages between poverty and disease, our study offers relevant guidance for potentially successful health promotion interventions.

Environmental and socio-demographic individual, family and neighborhood factors associated with children intestinal parasitoses at Iguazú, in the subtropical northern border of Argentina

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Maria Romina Rivero, Carlos De Angelo, Pablo Nuñez, Martín Salas, Carlos E. Motta, Alicia Chiaretta, Oscar D. Salomón, Song Liang

Background

Intestinal parasitoses are a major concern for public health, especially in children from middle and low-income populations of tropical and subtropical areas. We examined the presence and co-infection of parasites in humans as well as parasitic environmental contamination in Puerto Iguazú, Argentina. We explored the environmental and socio-demographic characteristics of the persistence of parasites in children and their environment.

Methodology/Principal findings

This cross-section survey was conducted among children population comprised into the area of the public health care centers of Iguazú during June 2013 to May 2016. Copro-parasitological status of 483 asymptomatic children was assessed. Simultaneously, a design-based sampling of 744 soil samples and 530 dog feces was used for characterize the environmental contamination. The 71.5% of these sites were contaminated. Sixteen genera were detected in the environment being hookworms (62.0%) the main pathogens group detected followed by Toxocara spp (16.3%), Trichuris spp (15.2%) and Giardia (6.5%). Total children prevalence raised 58.8%, detecting twelve genera of parasite with Giardia intestinalis as the most prevalent pathogen (29.0%) followed by Enterobius vermicularis (23.0%), Hymenolepis nana (12.4%) and hookworms (4.4%). Through questionnaires and census data, we characterized the socio-demographics conditions at an individual, family and neighborhood levels. A multi-level analysis including environmental contamination data showed that the ´presence of parasites´ was mostly determined by individual (e.g. age, playing habits, previous treatment) and household level (e.g. UBN, WASH, mother's literacy) determinants. Remarkably, to define the level of ‘parasite co-infection’, besides individual and household characteristics, environmental factors at a neighborhood level were important.

Conclusion/Significance

Our work represents the major survey of intestinal parasites in human and environmental samples developed in the region. High prevalence was detected in the children population as well as in their environment. This work shows the importance of considering and promoting multi-level actions over the identified determinants to face this public health problem from integrative approaches.

Prevalence and risk factors associated with <i>Leishmania</i> infection in Trang Province, southern Thailand

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Jipada Manomat, Saovanee Leelayoova, Lertwut Bualert, Peerapan Tan-ariya, Suradej Siripattanapipong, Mathirut Mungthin, Tawee Naaglor, Phunlerd Piyaraj

Background

Autochthonous cutaneous and visceral leishmaniasis (VL) caused by Leishmania martiniquensis and Leishmania siamensis have been considered emerging infectious diseases in Thailand. The disease burden is significantly underestimated, especially the prevalence of Leishmania infection among HIV-positive patients.

Methods

A cross-sectional study was conducted to determine the prevalence and risk factors associated with Leishmania infection among patients with HIV/AIDS living in Trang province, southern Thailand, between 2015 and 2016. Antibodies against Leishmania infection were assayed using the direct agglutination test (DAT). DNA of Leishmania was detected by ITS1-PCR using the buffy coat. Species of Leishmania were also identified.

Results

Of 724 participants, the prevalence of Leishmania infection was 25.1% (182/724) using either DAT and/or PCR assays. Seroprevalence of Leishmania infection was 18.5% (134/724), while Leishmania DNA detected by the PCR method was 8.4% (61/724). Of these, 24.9% (180/724) were asymptomatic, whereas 0.3% (2/724) were symptomatic VL and VL/CL (cutaneous leishmaniosis). At least five species were identified: L siamensis, L. martiniquensis, L. donovani complex, L. lainsoni, and L. major. Multivariate analysis showed that CD4+ levels <500 cells/μL and living in stilt houses were independently associated with Leishmania infection. Those who were PCR positive for Leishmania DNA were significantly associated with a detectable viral load, whereas non-injection drug use (NIDU) and CD4+ levels <500 cells/μL were potential risk factors of Leishmania seropositivity.

Conclusions

A magnitude of the prevalence of underreporting Leishmania infection among Thai patients with HIV was revealed in this study. Effective public health policy to prevent and control disease transmission is urgently needed.

Liposomal amphotericin B in travelers with cutaneous and muco-cutaneous leishmaniasis: Not a panacea

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Romain Guery, Benoit Henry, Guillaume Martin-Blondel, Claire Rouzaud, Florence Cordoliani, Gundel Harms, Jean-Pierre Gangneux, Françoise Foulet, Emmanuelle Bourrat, Michel Baccard, Gloria Morizot, Paul-Henri Consigny, Antoine Berry, Johannes Blum, Olivier Lortholary, Pierre Buffet, the French Cutaneous Leishmaniasis Study group & the LeishMan network

Background

Complex cutaneous and muco-cutaneous leishmaniasis (CL and MCL) often requires systemic therapy. Liposomal amphotericin B (L-AmB) has a strong potential for a solid clinical benefit in this indication.

Methods

We conducted a retrospective analysis of data from a French centralized referral treatment program and from the “LeishMan” European consortium database. All patients with parasitologically proven CL or MCL who received at least one dose of L-AmB were included. Positive outcome was based on ulcer closure as per recent WHO workshop guidelines.

Results

From 2008 through 2016, 43 travelers returning from 18 countries (Old World n = 28; New World n = 15) were analyzed with a median follow-up duration of 79 days [range 28–803]. Main clinical forms were: localized CL with one or multiple lesions (n = 32; 74%) and MCL (n = 8; 19%). As per published criteria 19 of 41 patients (46%) were cured 90 days after one course of L-AmB. When the following items -improvement before day 90 but no subsequent follow-up, delayed healing (>3 months) and healing after a second course of L-AmB- were included in the definition of cure, 27 of 43 patients (63%) had a positive outcome. Five patients (MCL = 1; CL = 4) experienced a relapse after a median duration of 6 months [range 3–27] post treatment and 53% of patients (23/43) experienced at least one adverse event including severe hypokalaemia and acute cardiac failure (one patient each). In multivariate analysis, tegumentary infection with L. infantum was associated with complete healing after L-AmB therapy (OR 5.8 IC 95% [1.03–32]) while infection with other species had no impact on outcome.

Conclusion

In conditions close to current medical practice, the therapeutic window of L-AmB was narrow in travellers with CL or MCL, with the possible exception of those infected with L. infantum. Strict follow-up is warranted when using L-AmB in patients with mild disease.

Analysis of the interactome of <i>Schistosoma mansoni</i> histone deacetylase 8

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Stéphanie Caby, Lucile Pagliazzo, Julien Lancelot, Jean-Michel Saliou, Nicolas Bertheaume, Raymond J. Pierce, Emmanuel Roger

Background

Histone deacetylase 8 from Schistosoma mansoni (SmHDAC8) is essential to parasite growth and development within the mammalian host and is under investigation as a target for the development of selective inhibitors as novel schistosomicidal drugs. Although some protein substrates and protein partners of human HDAC8 have been characterized, notably indicating a role in the function of the cohesin complex, nothing is known of the partners and biological function of SmHDAC8.

Methodology/Principal findings

We therefore employed two strategies to characterize the SmHDAC8 interactome. We first used SmHDAC8 as a bait protein in yeast two-hybrid (Y2H) screening of an S. mansoni cDNA library. This allowed the identification of 49 different sequences encoding proteins. We next performed co-immunoprecipitation (Co-IP) experiments on parasite extracts with an anti-SmHDAC8 antibody. Mass spectrometry (MS) analysis allowed the identification of 160 different proteins.

Conclusions/Significance

SmHDAC8 partners are involved in about 40 different processes, included expected functions such as the cohesin complex, cytoskeleton organization, transcriptional and translational regulation, metabolism, DNA repair, the cell cycle, protein dephosphorylation, proteolysis, protein transport, but also some proteasome and ribosome components were detected. Our results show that SmHDAC8 is a versatile deacetylase, potentially involved in both cytosolic and nuclear processes.

Development and preliminary evaluation of a multiplexed amplification and next generation sequencing method for viral hemorrhagic fever diagnostics

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Annika Brinkmann, Koray Ergünay, Aleksandar Radonić, Zeliha Kocak Tufan, Cristina Domingo, Andreas Nitsche

Background

We describe the development and evaluation of a novel method for targeted amplification and Next Generation Sequencing (NGS)-based identification of viral hemorrhagic fever (VHF) agents and assess the feasibility of this approach in diagnostics.

Methodology

An ultrahigh-multiplex panel was designed with primers to amplify all known variants of VHF-associated viruses and relevant controls. The performance of the panel was evaluated via serially quantified nucleic acids from Yellow fever virus, Rift Valley fever virus, Crimean-Congo hemorrhagic fever (CCHF) virus, Ebola virus, Junin virus and Chikungunya virus in a semiconductor-based sequencing platform. A comparison of direct NGS and targeted amplification-NGS was performed. The panel was further tested via a real-time nanopore sequencing-based platform, using clinical specimens from CCHF patients.

Principal findings

The multiplex primer panel comprises two pools of 285 and 256 primer pairs for the identification of 46 virus species causing hemorrhagic fevers, encompassing 6,130 genetic variants of the strains involved. In silico validation revealed that the panel detected over 97% of all known genetic variants of the targeted virus species. High levels of specificity and sensitivity were observed for the tested virus strains. Targeted amplification ensured viral read detection in specimens with the lowest virus concentration (1–10 genome equivalents) and enabled significant increases in specific reads over background for all viruses investigated. In clinical specimens, the panel enabled detection of the causative agent and its characterization within 10 minutes of sequencing, with sample-to-result time of less than 3.5 hours.

Conclusions

Virus enrichment via targeted amplification followed by NGS is an applicable strategy for the diagnosis of VHFs which can be adapted for high-throughput or nanopore sequencing platforms and employed for surveillance or outbreak monitoring.

The Asian house shrew <i>Suncus murinus</i> as a reservoir and source of human outbreaks of plague in Madagascar

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Soanandrasana Rahelinirina, Minoarisoa Rajerison, Sandra Telfer, Cyril Savin, Elisabeth Carniel, Jean-Marc Duplantier

Identifying key reservoirs for zoonoses is crucial for understanding variation in incidence. Plague re-emerged in Mahajanga, Madagascar in the 1990s but there has been no confirmed case since 1999. Here we combine ecological and genetic data, from during and after the epidemics, with experimental infections to examine the role of the shrew Suncus murinus in the plague epidemiological cycle. The predominance of S. murinus captures during the epidemics, their carriage of the flea vector and their infection with Yersinia pestis suggest they played an important role in the maintenance and transmission of plague. S. murinus exhibit a high but variable resistance to experimental Y. pestis infections, providing evidence of its ability to act as a maintenance host. Genetic analyses of the strains isolated from various hosts were consistent with two partially-linked transmission cycles, with plague persisting within the S. murinus population, occasionally spilling over into the rat and human populations. The recent isolation from a rat in Mahajanga of a Y. pestis strain genetically close to shrew strains obtained during the epidemics reinforces this hypothesis and suggests circulation of plague continues. The observed decline in S. murinus and Xenopsylla cheopis since the epidemics appears to have decreased the frequency of spillover events to the more susceptible rats, which act as a source of infection for humans. Although this may explain the lack of confirmed human cases in recent years, the current circulation of plague within the city highlights the continuing health threat.

Molecular characterization of tsetse’s proboscis and its response to <i>Trypanosoma congolense</i> infection

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Erick O. Awuoche, Brian L. Weiss, Aurélien Vigneron, Paul O. Mireji, Emre Aksoy, Benson Nyambega, Geoffrey M. Attardo, Yineng Wu, Michelle O’Neill, Grace Murilla, Serap Aksoy

Tsetse flies (Glossina spp.) transmit parasitic African trypanosomes (Trypanosoma spp.), including Trypanosoma congolense, which causes animal African trypanosomiasis (AAT). AAT detrimentally affects agricultural activities in sub-Saharan Africa and has negative impacts on the livelihood and nutrient availability for the affected communities. After tsetse ingests an infectious blood meal, T. congolense sequentially colonizes the fly’s gut and proboscis (PB) organs before being transmitted to new mammalian hosts during subsequent feedings. Despite the importance of PB in blood feeding and disease transmission, little is known about its molecular composition, function and response to trypanosome infection. To bridge this gap, we used RNA-seq analysis to determine its molecular characteristics and responses to trypanosome infection. By comparing the PB transcriptome to whole head and midgut transcriptomes, we identified 668 PB-enriched transcripts that encoded proteins associated with muscle tissue, organ development, chemosensation and chitin-cuticle structure development. Moreover, transcripts encoding putative mechanoreceptors that monitor blood flow during tsetse feeding and interact with trypanosomes were also expressed in the PB. Microscopic analysis of the PB revealed cellular structures associated with muscles and cells. Infection with T. congolense resulted in increased and decreased expression of 38 and 88 transcripts, respectively. Twelve of these differentially expressed transcripts were PB-enriched. Among the transcripts induced upon infection were those encoding putative proteins associated with cell division function(s), suggesting enhanced tissue renewal, while those suppressed were associated with metabolic processes, extracellular matrix and ATP-binding as well as immunity. These results suggest that PB is a muscular organ with chemosensory and mechanosensory capabilities. The mechanoreceptors may be point of PB-trypanosomes interactions. T. congolense infection resulted in reduced metabolic and immune capacity of the PB. The molecular knowledge on the composition and putative functions of PB forms the foundation to identify new targets to disrupt tsetse’s ability to feed and parasite transmission.

Progress towards a leprosy-free country: the experience of Oman

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Salah T Al Awaidy

Introduction

The World Health Organization (WHO) released the Global Leprosy Strategy 2016–2020 towards a leprosy-free world. The author described the progress made towards the elimination of leprosy and suggested recommendations for the acceleration towards a Leprosy-free country according to WHO laid out criterion.

Methodology

Case record review of Leprosy patients managed between the years 1992 to 2015 were registered and analyzed. Data were collected from annual reports of the Ministry of Health including demographics, classification of leprosy new cases, relapse, childhood, grades of disability (GD) and multidrug therapy (MDT) completion rates.

Results

Leprosy prevalence rate declined from 1.64 to 0.09 per 10,000 population during the period 1992 and 2015 (p<0.0001). Between 2005 and 2015, 77 patients were diagnosed with Leprosy as per definition and 75/77 (98%) had smear or biopsy positive. Of these, 53 (69%) cases were among foreign-born (non-national) (p<0.003) and 19 (25%) were among women. Most of the leprosy cases were notified in Muscat governorate 29 (38%) and among patients between 25–44 years of age 41 (53%), followed by ≥45 years 29 (38%) and 6 (8%) were children age ≤ 14 years. Multi-bacillary (MB) cases reported 60 versus 17 for Pauci-bacillary (PB) (p< 0.01), while MB was highest among both nationals (83%) and foreign-born (75%).MDT completion rate was 100% and no relapse cases were notified among nationals. The rate of new patients diagnosed with leprosy related disability was 2.3 per million population, and grade 2 disability (G2D) rate among nationals was 0.9 per million population. No disability was recorded among women or children less than 14 years within the nationals group from 2013. Almost all the foreign-born patients didn’t complete their treatment in Oman as they left the country shortly after diagnosis of leprosy due to a very short term contract, discretionary employment practices by the employers and prefer to go home to complete their treatment.

Conclusion

Oman has met the elimination goals and made great strides towards becoming a leprosy-free country. However, challenges such as improving surveillance system efficiency and sensitivity for detecting timely leprosy cases, as well as foreign-born workers are still a major concerns.

Allopurinol attenuates acute kidney injury following <i>Bothrops jararaca</i> envenomation

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Pedro Henrique França Gois, Monique Silva Martines, Daniela Ferreira, Rildo Volpini, Daniele Canale, Ceila Malaque, Renato Crajoinas, Adriana Castello Costa Girardi, Maria Heloisa Massola Shimizu, Antonio Carlos Seguro

Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI) with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo) in an experimental model of Bothrops jararaca venom (BJ)-associated AKI. Five groups of Wistar rats were studied: Sham, Allo, BJ, BJ+Allo, BJ+ipAllo. BJ (0.25 mg/kg) was intravenously injected during 40’. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L) in the drinking water 7 days prior to Saline or BJ infusion respectively. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg) 40’ after BJ infusion. BJ rats showed markedly reduced glomerular filtration rate (GFR, inulin clearance) associated with intense renal vasoconstriction, hemolysis, hemoglobinuria, reduced glutathione and increased systemic and renal markers of nitro-oxidative stress (Nitrotyrosine). Allo ameliorated GFR, renal blood flow (RBF), renal vascular resistance and arterial lactate levels. In addition, Allo was associated with increased serum glutathione as well as reduced levels of plasma and renal Nitrotyrosine. Our data show that Allo attenuated BJ-associated AKI, reduced oxidative stress, improved renal hemodynamics and organ perfusion. It might represent a novel adjuvant approach for Bothrops envenomation, a new use for an old and widely available drug.

Programmatic factors associated with the limited impact of community-directed treatment with Ivermectin to control Onchocerciasis in three drainage basins of South West Cameroon

PLoS Neglected Tropical Diseases News - 20 November 2017 - 10:00pm

by Christian Tetteh Duamor, Fabrice Roberto Datchoua-Poutcheu, Winston Patrick Chounna Ndongmo, Aldof Tah Yoah, Ernest Njukang, Emmanuel Kah, Mary Sheena Maingeh, Jonas Arnaud Kengne-Ouaffo, Dizzle Bita Tayong, Peter A. Enyong, Samuel Wanji

Introduction

The CDTI model is known to have enhanced community participation in planning and resource mobilization toward the control of onchocerciasis. These effects were expected to translate into better individual acceptance of the intervention and hence high Treatment Coverage, leading to a sustainable community-led strategy and reduction in the disease burden. A survey revealed that after 10–12 rounds of treatment, prevalence of onchocerciasis was still high in three drainage basins of South West Cameroon and transmission was going on.

Methods

We designed a three (3)-year retrospective (2012, 2013 and 2014), descriptive cross-sectional study to explore the roles of operational challenges in the failure of CDTI to control the disease as expected. We administered 83 semi-structured questionnaires and conducted 12 in-depth interviews with Chiefs of Bureau Health, Chiefs of Centers, CDDs and Community Heads. Descriptive statistics was used to explore indicators of performance which were supported with views from in-depth interviews.

Results

We found that community participation was weak; communities were not deciding time and mode of distributions. Only 6 (15.0%) of 40 Community Drug Distributors reported they were selected at general community meetings as required. The health service was not able to meet and discuss Community-Directed Treatment with Ivermectin activities with individual communities partly due to transportation challenges; this was mostly done through letters. Funding was reported to be inadequate and not timely. Funds were not available to conduct Community-Self Monitoring after the 2014 Mass Drug Administration. There was inadequate health staff at the frontline health facility levels, and some Chiefs of Center reported that Community-Directed Treatment with Ivermectin work was too much for them. The mean operational Community Drug Distributor-population ratio was 1 Community Drug Distributor per 317 populations (range: 194–464, expected is 1:250). Community Drug Distributor attrition rate was 14% (2012), 11% (2013) and 12% (2014) of total Community Drug Distributors trained in the region. Lack of incentive for Community Drug Distributor was primary reason for Community Drug Distributor attrition. Number of Community Drug Distributors trained together by health area ranged from 14 to 127 (mean ± SD = 51 ±32) with duration of training ranging from 4–7 hours (mean ± SD = 5.05 ± 1.09). The trainings were conducted at the health centers. Community Drug Distributors always conducted census during the past three distributions (Mean ± SD = 2.85 ± 0.58). Community-Self Monitoring was facing challenge. Several of the community heads, Chiefs of Bureau Health and Chiefs of Center agreed that Community-Self Monitoring was not being carried out effectively due to lack of incentives for monitors in the communities.

Conclusion

Inadequate human resource, funding issues and transportation challenges during distribution periods reduced the ability of the health service to thoroughly sensitize communities and supervise CDTI activities. This resulted in weak community understanding, acceptance and participation in the process. CDTI in our study area did not achieve sustainable community-led campaign and this may have led to the reduced impact on Onchocerciasis.

The introduction of dengue follows transportation infrastructure changes in the state of Acre, Brazil: A network-based analysis

PLoS Neglected Tropical Diseases News - 17 November 2017 - 10:00pm

by Raquel Martins Lana, Marcelo Ferreira da Costa Gomes, Tiago França Melo de Lima, Nildimar Alves Honório, Cláudia Torres Codeço

Human mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment. To understand this process, we assess data from dengue national and municipal basins regarding population and demographics, transportation network, human mobility, and Ae. aegypti monitoring for the Brazilian state of Acre since the first recorded dengue case in the year 2000 to the year 2015. During this period, several changes in Acre’s transport infrastructure and urbanization have been started. To reconstruct the process of dengue introduction in Acre, we propose an analytic framework based on concepts used in malaria literature, namely vulnerability and receptivity, to inform risk assessments in dengue-free regions as well as network theory concepts for disease invasion and propagation. We calculate the probability of dengue importation to Acre from other Brazilian states, the evolution of dengue spread between Acrean municipalities and dengue establishment in the state. Our findings suggest that the landscape changes associated with human mobility have created favorable conditions for the establishment of dengue virus transmission in Acre. The revitalization of its major roads, as well as the increased accessibility by air to and within the state, have increased dengue vulnerability. Unplanned urbanization and population growth, as observed in Acre during the period of study, contribute to ideal conditions for Ae. aegypti mosquito establishment, increase the difficulty in mosquito control and consequently its local receptivity.

Mycolactone displays anti-inflammatory effects on the nervous system

PLoS Neglected Tropical Diseases News - 17 November 2017 - 10:00pm

by Caroline Isaac, Annie Mauborgne, Alfonso Grimaldi, Kemy Ade, Michel Pohl, Cristina Limatola, Yves Boucher, Caroline Demangel, Laure Guenin-Macé

Background

Mycolactone is a macrolide produced by the skin pathogen Mycobacterium ulcerans, with cytotoxic, analgesic and immunomodulatory properties. The latter were recently shown to result from mycolactone blocking the Sec61-dependent production of pro-inflammatory mediators by immune cells. Here we investigated whether mycolactone similarly affects the inflammatory responses of the nervous cell subsets involved in pain perception, transmission and maintenance. We also investigated the effects of mycolactone on the neuroinflammation that is associated with chronic pain in vivo.

Methodology/ Principle findings

Sensory neurons, Schwann cells and microglia were isolated from mice for ex vivo assessment of mycolactone cytotoxicity and immunomodulatory activity by measuring the production of proalgesic cytokines and chemokines. In all cell types studied, prolonged (>48h) exposure to mycolactone induced significant cell death at concentrations >10 ng/ml. Within the first 24h treatment, nanomolar concentrations of mycolactone efficiently suppressed the cell production of pro-inflammatory mediators, without affecting their viability. Notably, mycolactone also prevented the pro-inflammatory polarization of cortical microglia. Since these cells critically contribute to neuroinflammation, we next tested if mycolactone impacts this pathogenic process in vivo. We used a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. Here, mycolactone was injected daily for 3 days in the spinal canal, to ensure its proper delivery to spinal cord. While this treatment failed to prevent injury-induced neuroinflammation, it decreased significantly the local production of inflammatory cytokines without inducing detectable cytotoxicity.

Conclusion/ Significance

The present study provides in vitro and in vivo evidence that mycolactone suppresses the inflammatory responses of sensory neurons, Schwann cells and microglia, without affecting the cell viability. Together with previous studies using peripheral blood leukocytes, our work implies that mycolactone-mediated analgesia may, at least partially, be explained by its anti-inflammatory properties.

Longitudinal survey of two serotine bat (<i>Eptesicus serotinus</i>) maternity colonies exposed to EBLV-1 (European Bat Lyssavirus type 1): Assessment of survival and serological status variations using capture-recapture models

PLoS Neglected Tropical Diseases News - 17 November 2017 - 10:00pm

by Emmanuelle Robardet, Christophe Borel, Marie Moinet, Dorothée Jouan, Marine Wasniewski, Jacques Barrat, Franck Boué, Elodie Montchâtre-Leroy, Alexandre Servat, Olivier Gimenez, Florence Cliquet, Evelyne Picard-Meyer

This study describes two longitudinal serological surveys of European Bat Lyssavirus type 1 (EBLV-1) antibodies in serotine bat (Eptesicus serotinus) maternity colonies located in the North-East of France. This species is currently considered as the main EBLV-1 reservoir. Multievent capture-recapture models were used to determine the factors influencing bat rabies transmission as this method accounts for imperfect detection and uncertainty in disease states. Considering the period of study, analyses revealed that survival and recapture probabilities were not affected by the serological status of individuals, confirming the capacity of bats to be exposed to lyssaviruses without dying. Five bats have been found with EBLV-1 RNA in the saliva at the start of the study, suggesting they were caught during virus excretion period. Among these bats, one was interestingly recaptured one year later and harbored a seropositive status. Along the survey, some others bats have been observed to both seroconvert (i.e. move from a negative to a positive serological status) and serorevert (i.e. move from a positive to a negative serological status). Peak of seroprevalence reached 34% and 70% in site A and B respectively. On one of the 2 sites, global decrease of seroprevalence was observed all along the study period nuanced by oscillation intervals of approximately 2–3 years supporting the oscillation infection dynamics hypothesized during a previous EBLV-1 study in a Myotis myotis colony. Seroprevalence were affected by significantly higher seroprevalence in summer than in spring. The maximum time observed between successive positive serological statuses of a bat demonstrated the potential persistence of neutralizing antibodies for at least 4 years. At last, EBLV-1 serological status transitions have been shown driven by age category with higher seroreversion frequencies in adults than in juvenile. Juveniles and female adults seemed indeed acting as distinct drivers of the rabies virus dynamics, hypothesis have been addressed but their exact role in the EBLV-1 transmission still need to be specified.

Detection of relapsing fever <i>Borrelia</i> spp., <i>Bartonella</i> spp. and Anaplasmataceae bacteria in argasid ticks in Algeria

PLoS Neglected Tropical Diseases News - 16 November 2017 - 10:00pm

by Ismail Lafri, Basma El Hamzaoui, Idir Bitam, Hamza Leulmi, Reda Lalout, Oleg Mediannikov, Mohamed Chergui, Mohamed Karakellah, Didier Raoult, Philippe Parola

Background

Argasid ticks (soft ticks) are blood-feeding arthropods that can parasitize rodents, birds, humans, livestock and companion animals. Ticks of the Ornithodoros genus are known to be vectors of relapsing fever borreliosis in humans. In Algeria, little is known about relapsing fever borreliosis and other bacterial pathogens transmitted by argasid ticks.

Methodology/Principal findings

Between May 2013 and October 2015, we investigated the presence of soft ticks in 20 rodent burrows, 10 yellow-legged gull (Larus michahellis) nests and animal shelters in six locations in two different bioclimatic zones in Algeria. Six species of argasid ticks were identified morphologically and through 16S rRNA gene sequencing. The presence and prevalence of Borrelia spp., Bartonella spp., Rickettsia spp. and Anaplasmataceae was assessed by qPCR template assays in each specimen. All qPCR-positive samples were confirmed by standard PCR, followed by sequencing the amplified fragments. Two Borrelia species were identified: Borrelia hispanica in Ornithodoros occidentalis in Mostaganem, and Borrelia cf. turicatae in Carios capensis in Algiers. One new Bartonella genotype and one new Anaplasmataceae genotype were also identified in Argas persicus.

Conclusions

The present study highlights the presence of relapsing fever borreliosis agents, although this disease is rarely diagnosed in Algeria. Other bacteria of unknown pathogenicity detected in argasid ticks which may bite humans deserve further investigation.

Conservation of a microRNA cluster in parasitic nematodes and profiling of miRNAs in excretory-secretory products and microvesicles of <i>Haemonchus contortus</i>

PLoS Neglected Tropical Diseases News - 16 November 2017 - 10:00pm

by Henry Y. Gu, Neil D. Marks, Alan D. Winter, William Weir, Thomas Tzelos, Tom N. McNeilly, Collette Britton, Eileen Devaney

microRNAs are small non-coding RNAs that are important regulators of gene expression in a range of animals, including nematodes. We have analysed a cluster of four miRNAs from the pathogenic nematode species Haemonchus contortus that are closely linked in the genome. We find that the cluster is conserved only in clade V parasitic nematodes and in some ascarids, but not in other clade III species nor in clade V free-living nematodes. Members of the cluster are present in parasite excretory-secretory products and can be detected in the abomasum and draining lymph nodes of infected sheep, indicating their release in vitro and in vivo. As observed for other parasitic nematodes, H. contortus adult worms release extracellular vesicles (EV). Small RNA libraries were prepared from vesicle-enriched and vesicle-depleted supernatants from both adult worms and L4 stage larvae. Comparison of the miRNA species in the different fractions indicated that specific miRNAs are packaged within vesicles, while others are more abundant in vesicle-depleted supernatant. Hierarchical clustering analysis indicated that the gut is the likely source of vesicle-associated miRNAs in the L4 stage, but not in the adult worm. These findings add to the growing body of work demonstrating that miRNAs released from parasitic helminths may play an important role in host-parasite interactions.

Drivers of house invasion by sylvatic Chagas disease vectors in the Amazon-Cerrado transition: A multi-year, state-wide assessment of municipality-aggregated surveillance data

PLoS Neglected Tropical Diseases News - 16 November 2017 - 10:00pm

by Raíssa N. Brito, David E. Gorla, Liléia Diotaiuti, Anália C. F. Gomes, Rita C. M. Souza, Fernando Abad-Franch

Background

Insecticide spraying efficiently controls house infestation by triatomine bugs, the vectors of Trypanosoma cruzi. The strategy, however, is ineffective against sylvatic triatomines, which can transmit Chagas disease by invading (without colonizing) man-made structures. Despite growing awareness of the relevance of these transmission dynamics, the drivers of house invasion by sylvatic triatomines remain poorly understood.

Methods/Findings

About 12,000 sylvatic triatomines were caught during routine surveillance in houses of Tocantins state, Brazil, in 2005–2013. Using negative binomial regression, information-theoretic model evaluation/averaging, and external model validation, we investigated the effects of regional (Amazon/Cerrado), landscape (preservation/disturbance), and climate covariates (temperature, rainfall) on the municipality-aggregated numbers of house-invading Rhodnius pictipes, R. robustus, R. neglectus, and Panstrongylus geniculatus. House invasion by R. pictipes and R. robustus was overall more frequent in the Amazon biome, tended to increase in municipalities with more well-preserved land, and decreased in rainier municipalities. Across species, invasion decreased with higher landscape-disturbance levels and in hotter-day municipalities. Invasion by R. neglectus and P. geniculatus increased somewhat with more land at intermediate disturbance and peaked in average-rainfall municipalities. Temperature effects were more pronounced on P. geniculatus than on Rhodnius spp.

Conclusions

We report widespread, frequent house invasion by sylvatic triatomines in the Amazon–Cerrado transition. Our analyses indicate that readily available environmental metrics may help predict the risk of contact between sylvatic triatomines and humans at coarse geographic scales, and hint at specific hypotheses about climate and deforestation effects on those vectors–with some taxon-specific responses and some seemingly general trends. Thus, our focal species appear to be quite sensitive to higher temperatures, and might be less common in more heavily-disturbed than in better-preserved environments. This study illustrates, in sum, how entomological routine-surveillance data can be efficiently used for Chagas disease risk prediction and stratification when house-colonizing vectors are absent.

Zika virus: An updated review of competent or naturally infected mosquitoes

PLoS Neglected Tropical Diseases News - 16 November 2017 - 10:00pm

by Yanouk Epelboin, Stanislas Talaga, Loïc Epelboin, Isabelle Dusfour

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) that recently caused outbreaks in the Americas. Over the past 60 years, this virus has been observed circulating among African, Asian, and Pacific Island populations, but little attention has been paid by the scientific community until the discovery that large-scale urban ZIKV outbreaks were associated with neurological complications such as microcephaly and several other neurological malformations in fetuses and newborns. This paper is a systematic review intended to list all mosquito species studied for ZIKV infection or for their vector competence. We discuss whether studies on ZIKV vectors have brought enough evidence to formally exclude other mosquitoes than Aedes species (and particularly Aedes aegypti) to be ZIKV vectors. From 1952 to August 15, 2017, ZIKV has been studied in 53 mosquito species, including 6 Anopheles, 26 Aedes, 11 Culex, 2 Lutzia, 3 Coquillettidia, 2 Mansonia, 2 Eretmapodites, and 1 Uranotaenia. Among those, ZIKV was isolated from 16 different Aedes species. The only species other than Aedes genus for which ZIKV was isolated were Anopheles coustani, Anopheles gambiae, Culex perfuscus, and Mansonia uniformis. Vector competence assays were performed on 22 different mosquito species, including 13 Aedes, 7 Culex, and 2 Anopheles species with, as a result, the discovery that A. aegypti and Aedes albopictus were competent for ZIKV, as well as some other Aedes species, and that there was a controversy surrounding Culex quinquefasciatus competence. Although Culex, Anopheles, and most of Aedes species were generally observed to be refractory to ZIKV infection, other potential vectors transmitting ZIKV should be explored.

Post-kala-azar dermal leishmaniasis in the Indian subcontinent: A threat to the South-East Asia Region Kala-azar Elimination Programme.

PLoS Neglected Tropical Diseases News - 16 November 2017 - 10:00pm

by Eduard E. Zijlstra, Fabiana Alves, Suman Rijal, Byron Arana, Jorge Alvar

Background

The South-East Asia Region Kala-azar Elimination Programme (KAEP) is expected to enter the consolidation phase in 2017, which focuses on case detection, vector control, and identifying potential sources of infection. Post-kala-azar dermal leishmaniasis (PKDL) is thought to play a role in the recurrence of visceral leishmaniasis (VL)/kala-azar outbreaks, and control of PKDL is among the priorities of the KAEP.

Methodology and principal finding

We reviewed the literature with regard to PKDL in Asia and interpreted the findings in relation to current intervention methods in the KAEP in order to make recommendations. There is a considerable knowledge gap regarding the pathophysiology of VL and PKDL, especially the underlying immune responses. Risk factors (of which previous VL treatments may be most important) are poorly understood and need to be better defined. The role of PKDL patients in transmission is largely unknown, and there is insufficient information about the importance of duration, distribution and severity of the rash, time of onset, and self-healing. Current intervention methods focus on active case detection and treatment of all PKDL cases with miltefosine while there is increasing drug resistance. The prevention of PKDL by improved VL treatment currently receives insufficient attention.

Conclusion and significance

PKDL is a heterogeneous and dynamic condition, and patients differ with regard to time of onset after VL, chronicity, and distribution and appearance of the rash, as well as immune responses (including tendency to self-heal), all of which may vary over time. It is essential to fully describe the pathophysiology in order to make informed decisions on the most cost-effective approach. Emphasis should be on early detection of those who contribute to transmission and those who are in need of treatment, for whom short-course, effective, and safe drug regimens should be available. The prevention of PKDL should be emphasised by innovative and improved treatment for VL, which may include immunomodulation.

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