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Added-value of mosquito vector breeding sites from street view images in the risk mapping of dengue incidence in Thailand

PLoS Neglected Tropical Diseases News - 8 March 2021 - 2:00pm

by Myat Su Yin, Dominique Bicout, Peter Haddawy, Johannes Schöning, Yongjua Laosiritaworn, Patiwat Sa-angchai

Dengue is an emerging vector-borne viral disease across the world. The primary dengue mosquito vectors breed in containers with sufficient water and nutrition. Outdoor containers can be detected from geotagged images using state-of-the-art deep learning methods. In this study, we utilize such container information from street view images in developing a risk mapping model and determine the added value of including container information in predicting dengue risk. We developed seasonal-spatial models in which the target variable dengue incidence was explained using weather and container variable predictors. Linear mixed models with fixed and random effects are employed in our models to account for different characteristics of containers and weather variables. Using data from three provinces of Thailand between 2015 and 2018, the models are developed at the sub-district level resolution to facilitate the development of effective targeted intervention strategies. The performance of the models is evaluated with two baseline models: a classic linear model and a linear mixed model without container information. The performance evaluated with the correlation coefficients, R-squared, and AIC shows the proposed model with the container information outperforms both baseline models in all three provinces. Through sensitivity analysis, we investigate the containers that have a high impact on dengue risk. Our findings indicate that outdoor containers identified from street view images can be a useful data source in building effective dengue risk models and that the resulting models have potential in helping to target container elimination interventions.

Machine-learning model led design to experimentally test species thermal limits: The case of kissing bugs (Triatominae)

PLoS Neglected Tropical Diseases News - 8 March 2021 - 2:00pm

by Jorge E. Rabinovich, Agustín Alvarez Costa, Ignacio J. Muñoz, Pablo E. Schilman, Nicholas M. Fountain-Jones

Species Distribution Modelling (SDM) determines habitat suitability of a species across geographic areas using macro-climatic variables; however, micro-habitats can buffer or exacerbate the influence of macro-climatic variables, requiring links between physiology and species persistence. Experimental approaches linking species physiology to micro-climate are complex, time consuming and expensive. E.g., what combination of exposure time and temperature is important for a species thermal tolerance is difficult to judge a priori. We tackled this problem using an active learning approach that utilized machine learning methods to guide thermal tolerance experimental design for three kissing-bug species: Triatoma infestans, Rhodnius prolixus, and Panstrongylus megistus (Hemiptera: Reduviidae: Triatominae), vectors of the parasite causing Chagas disease. As with other pathogen vectors, triatomines are well known to utilize micro-habitats and the associated shift in microclimate to enhance survival. Using a limited literature-collected dataset, our approach showed that temperature followed by exposure time were the strongest predictors of mortality; species played a minor role, and life stage was the least important. Further, we identified complex but biologically plausible nonlinear interactions between temperature and exposure time in shaping mortality, together setting the potential thermal limits of triatomines. The results from this data led to the design of new experiments with laboratory results that produced novel insights of the effects of temperature and exposure for the triatomines. These results, in turn, can be used to better model micro-climatic envelope for the species. Here we demonstrate the power of an active learning approach to explore experimental space to design laboratory studies testing species thermal limits. Our analytical pipeline can be easily adapted to other systems and we provide code to allow practitioners to perform similar analyses. Not only does our approach have the potential to save time and money: it can also increase our understanding of the links between species physiology and climate, a topic of increasing ecological importance.

Clinical and immunological characteristics of tegumentary leishmaniasis cases in Bolivia

PLoS Neglected Tropical Diseases News - 5 March 2021 - 2:00pm

by Cristina Ballart, Mary Cruz Torrico, Gisela Vidal, Faustino Torrico, Daniel Lozano, Montserrat Gállego, Lilian Pinto, Ernesto Rojas, Ruth Aguilar, Carlota Dobaño, Sonia Ares-Gomez, Albert Picado

Background

Tegumentary leishmaniasis (TL) is a parasitic disease that can present a cutaneous or mucocutaneous clinical form (CL and MCL, respectively). The disease is caused by different Leishmania species and transmitted by phlebotomine sand flies. Bolivia has one of the highest incidences of the disease in South America and the diagnosis is done by parasitological techniques. Our aim was to describe the clinical and immunological characteristics of CL and MCL patients attending the leishmaniasis reference center in Cochabamba, Bolivia, in order to gain updated clinical and epidemiological information, to evaluate the diagnostic methods used and to identify biomarkers related to clinical disease and its evolution.

Methodology/Principal findings

The study was conducted from September 2014 to November 2015 and 135 patients with lesions compatible with CL or MCL were included. Epidemiological and clinical data were collected using a semi-structured questionnaire. Two parasitological diagnostic methods were used: Giemsa-stained smears and culture of lesion aspirates. Blood samples obtained from participants were used to measure the concentrations of different cytokines. 59.2% (80/135) were leishmaniasis confirmed cases (CL: 71.3%; MCL: 28.7%). Sixty percent of the confirmed cases were positive by smears and 90.6% were positive by culture. 53.8% were primo-infections. Eotaxin and monokine induced by IFN-γ presented higher serum concentrations in the MCL clinical presentation compared to CL cases and no-cases. None of the cytokines presented different concentrations between primo-infections and secondary infections due to treatment failure.

Conclusions/Significance

In Bolivia, parasitological diagnosis remains the reference standard in diagnosis of leishmaniasis because of its high specificity, whereas the sensitivity varies over a wide range leading to loss of cases. Until more accurate tools are implemented, all patients should be tested by both smears and culture of lesion aspirates to minimize the risk of false negatives. Our results showed higher concentrations of several cytokines in MCL compared to CL, but no differences were observed between CL and no-cases. In addition, none of the cytokines differed between primary and secondary infections. These results highlight the need of further research to identify biomarkers of susceptibility and disease progression, in addition to looking at the local cellular immune responses in the lesions.

Zika virus disrupts the barrier structure and Absorption/Secretion functions of the epididymis in mice

PLoS Neglected Tropical Diseases News - 5 March 2021 - 2:00pm

by Ziyang Sheng, Na Gao, Dongying Fan, Na Wu, Yingying Zhang, Daishu Han, Yun Zhang, Weilong Tan, Peigang Wang, Jing An

Several studies have demonstrated that Zika virus (ZIKV) damages testis and leads to infertility in mice; however, the infection in the epididymis, another important organ of male reproductive health, has gained less attention. Previously, we detected lesions in the epididymis in interferon type I and II receptor knockout male mice during ZIKV infection. Herein, the pathogenesis of ZIKV in the epididymis was further assessed in the infected mice after footpad inoculation. ZIKV efficiently replicated in the epididymis, and principal cells were susceptible to ZIKV. ZIKV infection disrupted the histomorphology of the epididymis, and the effects were characterized by a decrease in the thickness of the epithelial layer and an increase in the luminal diameter, especially at the proximal end. Significant inflammatory cell infiltration was observed in the epididymis accompanied by an increase in the levels of interleukin (IL)-6 and IL-28. The expression of tight junction proteins was downregulated and associated with disordered arrangement of the junctions. Importantly, the expression levels of aquaporin 1 and lipocalin 8, indicators of the absorption and secretion functions of the epididymis, were markedly reduced, and the proteins were redistributed. These events synergistically altered the microenvironment for sperm maturation, disturbed sperm transport downstream, and may impact male reproductive health. Overall, these results provide new insights into the pathogenesis of the male reproductive damage caused by ZIKV infection and the possible contribution of epididymal injury into this process. Therefore, male fertility of the population in areas of ZIKV epidemic requires additional attention.

Practices in research, surveillance and control of neglected tropical diseases by One Health approaches: A survey targeting scientists from French-speaking countries

PLoS Neglected Tropical Diseases News - 4 March 2021 - 2:00pm

by Sophie Molia, Juliette Saillard, Koussai Dellagi, Florence Cliquet, Jean-Mathieu Bart, Brice Rotureau, Patrick Giraudoux, Jean Jannin, Patrice Debré, Philippe Solano

One health (OH) approaches have increasingly been used in the last decade in the fight against zoonotic neglected tropical diseases (NTDs). However, descriptions of such collaborations between the human, animal and environmental health sectors are still limited for French-speaking tropical countries. The objective of the current survey was to explore the diversity of OH experiences applied to research, surveillance and control of NTDs by scientists from French-speaking countries, and discuss their constraints and benefits. Six zoonotic NTDs were targeted: echinococcoses, trypanosomiases, leishmaniases, rabies, Taenia solium cysticercosis and leptospiroses. Invitations to fill in an online questionnaire were sent to members of francophone networks on NTDs and other tropical diseases. Results from the questionnaire were discussed during an international workshop in October 2019. The vast majority (98%) of the 171 respondents considered OH approaches relevant although only 64% had implemented them. Among respondents with OH experience, 58% had encountered difficulties mainly related to a lack of knowledge, interest and support for OH approaches by funding agencies, policy-makers, communities and researchers. Silos between disciplines and health sectors were still strong at both scientific and operational levels. Benefits were reported by 94% of respondents with OH experience, including increased intellectual stimulation, stronger collaborations, higher impact and cost-efficiency of interventions. Recommendations for OH uptake included advocacy, capacity-building, dedicated funding, and higher communities’ involvement. Improved research coordination by NTD networks, production of combined human-animal health NTD impact indicators, and transversal research projects on diagnostic and reservoirs were also considered essential.

A painful journey to antivenom: The therapeutic itinerary of snakebite patients in the Brazilian Amazon (The QUALISnake Study)

PLoS Neglected Tropical Diseases News - 4 March 2021 - 2:00pm

by Joseir Saturnino Cristino, Guilherme Maciel Salazar, Vinícius Azevedo Machado, Eduardo Honorato, Altair Seabra Farias, João Ricardo Nickenig Vissoci, Alexandre Vilhena Silva Neto, Marcus Lacerda, Fan Hui Wen, Wuelton Marcelo Monteiro, Jacqueline Almeida Gonçalves Sachett

Access to antivenoms is not guarranteed for vulnerable populations that inhabit remote areas in the Amazon. The study of therapeutic itineraries (TI) for treatment of snakebites would support strategies to provide timely access to users. A TI is the set of processes by which individuals adhere to certain forms of treatment, and includes the path traveled in the search for healthcare, and practices to solve their health problems. This study aims to describe TIs of snakebite patients in the Brazilian Amazon. This study was carried out at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, in Manaus, state of Amazonas, Brazil. The itinerary from the moment of the bite to the patient’s admission to the reference unit was analyzed. Sample size was defined by saturation. After an exploratory survey to collect epidemiological variables, in-depth interviews were conducted following a semi-structured guide. Patients originated from rural areas of 11 different municipalities, including ones located >500 kilometers from Manaus. A great fragmentation was observed in the itineraries, marked by several changes of means of transport along the route. Four themes emerged from the analysis: exposure to snakebite during day-to-day activities, use of traditional therapeutic practices, and personal perception of the severity, as well as the route taken and its contingencies. Access to healthcare requires considerable effort on the part of snakebite patients. Major barriers were identified, such as the low number of hospitals that offer antivenom treatment, poor access to healthcare due to long distances and geographic barriers, low acceptability of healthcare offered in countryside, lack of use of personal protective equipment, common use of ineffective or deleterious self-care practices, late recognition of serious clinical signs and resistance to seeking medical assistance. Health education, promotion of immediate transport to health centers and decentralization of antivenom from reference hospitals to community healthcare centers in the Brazilian Amazon are more effective strategies that would to maximize access to antivenom treatment.

Modelling the factors affecting the probability for local rabies elimination by strategic control

PLoS Neglected Tropical Diseases News - 4 March 2021 - 2:00pm

by Johann L. Kotzé, John Duncan Grewar, Aaron Anderson

Dog rabies has been recognized from ancient times and remains widespread across the developing world with an estimated 59,000 people dying annually from the disease. In 2011 a tri-partite alliance consisting of the OIE, the WHO and the FAO committed to globally eliminating dog-mediated human rabies by 2030. Regardless of global support, the responsibility remains with local program managers to implement successful elimination programs. It is well known that vaccination programs have a high probability of successful elimination if they achieve a population-coverage of 70%. It is often quoted that reducing population turnover (typically through sterilizations) raises the probability for local elimination by maintaining herd immunity for longer. Besides this, other factors that affect rabies elimination are rarely mentioned. This paper investigates the probability for local elimination as it relates to immunity, fecundity, dog population size, infectivity (bite rates), in-migration of immune-naïve dogs, and the initial incidence. To achieve this, an individual-based, stochastic, transmission model was manipulated to create a dataset covering combinations of factors that may affect elimination. The results thereof were analysed using a logistic regression model with elimination as the dependent variable. Our results suggest that smaller dog populations, lower infectivity and lower incidence (such as when epidemics start with single introductions) strongly increased the probability for elimination at wide ranges of vaccination levels. Lower fecundity and lower in-migration had weak effects. We discuss the importance of these findings in terms of their impact and their practical application in the design of dog-mediated rabies control programs.

Cost-effectiveness of the national dog rabies prevention and control program in Mexico, 1990–2015

PLoS Neglected Tropical Diseases News - 4 March 2021 - 2:00pm

by Jesús Felipe González-Roldán, Eduardo A. Undurraga, Martin I. Meltzer, Charisma Atkins, Fernando Vargas-Pino, Verónica Gutiérrez-Cedillo, José Ramón Hernández-Pérez

Background

Rabies is a viral zoonosis that imposes a substantial disease and economic burden in many developing countries. Dogs are the primary source of rabies transmission; eliminating dog rabies reduces the risk of exposure in humans significantly. Through mass annual dog rabies vaccination campaigns, the national program of rabies control in Mexico progressively reduced rabies cases in dogs and humans since 1990. In 2019, the World Health Organization validated Mexico for eliminating rabies as a public health problem. Using a governmental perspective, we retrospectively assessed the economic costs, effectiveness, and cost-effectiveness of the national program of rabies control in Mexico, 1990–2015.

Methodology

Combining various data sources, including administrative records, national statistics, and scientific literature, we retrospectively compared the current scenario of annual dog vaccination campaigns and post-exposure prophylaxis (PEP) with a counterfactual scenario without an annual dog vaccination campaign but including PEP. The counterfactual scenario was estimated using a mathematical model of dog rabies transmission (RabiesEcon). We performed a thorough sensitivity analysis of the main results.

Principal findings

Results suggest that in 1990 through 2015, the national dog rabies vaccination program in Mexico prevented about 13,000 human rabies deaths, at an incremental cost (MXN 2015) of $4,700 million (USD 300 million). We estimated an average cost of $360,000 (USD 23,000) per human rabies death averted, $6,500 (USD 410) per additional year-of-life, and $3,000 (USD 190) per dog rabies death averted. Results were robust to several counterfactual scenarios, including high and low rabies transmission scenarios and various assumptions about potential costs without mass dog rabies vaccination campaigns.

Conclusions

Annual dog rabies vaccination campaigns have eliminated the transmission of dog-to-dog rabies and dog-mediated human rabies deaths in Mexico. According to World Health Organization standards, our results show that the national program of rabies control in Mexico has been highly cost-effective.

Community-directed distributors—The “foot soldiers” in the fight to control and eliminate neglected tropical diseases

PLoS Neglected Tropical Diseases News - 4 March 2021 - 2:00pm

by Uche V. Amazigo, Stephen G. A. Leak, Honorat G. M. Zoure, Chukwu Okoronkwo, Maimouna Diop Ly, Sunday Isiyaku, Andy Crump, Joseph C. Okeibunor, Boakye Boatin

The neglected tropical diseases (NTDs) affect hundreds of millions of people, predominantly in rural, often difficult-to-access areas, poorly served by national health services. Here, we review the contributions of 4.8 million community-directed distributors (CDDs) of medicines over 2 decades in 146,000 communities in 27 sub-Saharan African countries to control or eliminate onchocerciasis and lymphatic filariasis (LF). We examine their role in the control of other NTDs, malaria, HIV/AIDS interventions, immunisation campaigns, and support to overstretched health service personnel. We are of the opinion that CDDs as community selected, trained, and experienced “foot soldiers,” some of whom were involved in the Ebola outbreak responses at the community level in Liberia, if retrained, can assist community leaders and support health workers (HWs) in the ongoing Coronavirus Disease 2019 (COVID-19) crisis. The review highlights the improved treatment coverage where there are women CDDs, the benefits and lessons from the work of CDDs, their long-term engagement, and the challenges they face in healthcare delivery. It underscores the value of utilising the CDD model for strong community engagement and recommends the model, with some review, to hasten the achievement of the NTD 2030 goal and assist the health system cope with evolving epidemics and other challenges. We propose that, based on the unprecedented progress made in the control of NTDs directly linked to community engagement and contributions of CDDs “foot soldiers,” they deserve regional and global recognition. We also suggest that the World Health Organization (WHO) and other international stakeholders promote policy and guidance for countries to adapt this model for the elimination of NTDs and to strengthen national health services. This will enhance the accomplishment of some Sustainable Development Goals (SDGs) by 2030 in sub-Saharan Africa.

Measuring the global burden of chikungunya and Zika viruses: A systematic review

PLoS Neglected Tropical Diseases News - 4 March 2021 - 2:00pm

by Christopher J. Puntasecca, Charles H. King, Angelle Desiree LaBeaud

Throughout the last decade, chikungunya virus (CHIKV) and Zika virus (ZIKV) infections have spread globally, causing a spectrum of disease that ranges from self-limited febrile illness to permanent severe disability, congenital anomalies, and early death. Nevertheless, estimates of their aggregate health impact are absent from the literature and are currently omitted from the Global Burden of Disease (GBD) reports. We systematically reviewed published literature and surveillance records to evaluate the global burden caused by CHIKV and ZIKV between 2010 and 2019, to calculate estimates of their disability-adjusted life year (DALY) impact. Extracted data on acute, chronic, and perinatal outcomes were used to create annualized DALY estimates, following techniques outlined in the GBD framework. This study is registered with PROSPERO (CRD42020192502). Of 7,877 studies identified, 916 were screened in detail, and 21 were selected for inclusion. Available data indicate that CHIKV and ZIKV caused the average yearly loss of over 106,000 and 44,000 DALYs, respectively, between 2010 and 2019. Both viruses caused substantially more burden in the Americas than in any other World Health Organization (WHO) region. This unequal distribution is likely due to a combination of limited active surveillance reporting in other regions and the lack of immunity that left the previously unexposed populations of the Americas susceptible to severe outbreaks during the last decade. Long-term rheumatic sequelae provided the largest DALY component for CHIKV, whereas congenital Zika syndrome (CZS) contributed most significantly for ZIKV. Acute symptoms and early mortality accounted for relatively less of the overall burden. Suboptimal reporting and inconsistent diagnostics limit precision when determining arbovirus incidence and frequency of complications. Despite these limitations, it is clear from our assessment that CHIKV and ZIKV represent a significant cause of morbidity that is not included in current disease burden reports. These results suggest that transmission-blocking strategies, including vector control and vaccine development, remain crucial priorities in reducing global disease burden through prevention of potentially devastating arboviral outbreaks.

Intestinal protozoan infections shape fecal bacterial microbiota in children from Guinea-Bissau

PLoS Neglected Tropical Diseases News - 3 March 2021 - 2:00pm

by Sebastian von Huth, Louise B. Thingholm, Poul-Erik Kofoed, Corinna Bang, Malte C. Rühlemann, Andre Franke, Uffe Holmskov

Intestinal parasitic infections, caused by helminths and protozoa, are globally distributed and major causes of worldwide morbidity. The gut microbiota may modulate parasite virulence and host response upon infection. The complex interplay between parasites and the gut microbiota is poorly understood, partly due to sampling difficulties in remote areas with high parasite burden. In a large study of children in Guinea-Bissau, we found high prevalence of intestinal parasites. By sequencing of the 16S rRNA genes of fecal samples stored on filter paper from a total of 1,204 children, we demonstrate that the bacterial microbiota is not significantly altered by helminth infections, whereas it is shaped by the presence of both pathogenic and nonpathogenic protozoa, including Entamoeba (E.) spp. and Giardia (G.) lamblia. Within-sample diversity remains largely unaffected, whereas overall community composition is significantly affected by infection with both nonpathogenic E. coli (R2 = 0.0131, P = 0.0001) and Endolimax nana (R2 = 0.00902, P = 0.0001), and by pathogenic E. histolytica (R2 = 0.0164, P = 0.0001) and G. lamblia (R2 = 0.00676, P = 0.0001). Infections with multiple parasite species induces more pronounced shifts in microbiota community than mild ones. A total of 31 bacterial genera across all four major bacterial phyla were differentially abundant in protozoan infection as compared to noninfected individuals, including increased abundance of Prevotella, Campylobacter and two Clostridium clades, and decreased abundance of Collinsella, Lactobacillus, Ruminococcus, Veillonella and one Clostridium clade. In the present study, we demonstrate that the fecal bacterial microbiota is shaped by intestinal parasitic infection, with most pronounced associations for protozoan species. Our results provide insights into the interplay between the microbiota and intestinal parasites, which are valuable to understand infection biology and design further studies aimed at optimizing treatment strategies.

The potential for histone deacetylase (HDAC) inhibitors as cestocidal drugs

PLoS Neglected Tropical Diseases News - 3 March 2021 - 2:00pm

by Hugo R. Vaca, Ana M. Celentano, María Agustina Toscanini, Tino Heimburg, Ehab Ghazy, Patrik Zeyen, Alexander-Thomas Hauser, Guilherme Oliveira, María C. Elissondo, Manfred Jung, Wolfgang Sippl, Federico Camicia, Mara Cecilia Rosenzvit

Background

Echinococcosis and cysticercosis are neglected tropical diseases caused by cestode parasites (family Taeniidae). Not only there is a small number of approved anthelmintics for the treatment of these cestodiases, but also some of them are not highly effective against larval stages, such that identifying novel drug targets and their associated compounds is critical. Histone deacetylase (HDAC) enzymes are validated drug targets in cancers and other diseases, and have been gaining relevance for developing new potential anti-parasitic treatments in the last years. Here, we present the anthelmintic profile for a panel of recently developed HDAC inhibitors against the model cestode Mesocestoides vogae (syn. M. corti).

Methodology/Principal findings

Phenotypic screening was performed on M. vogae by motility measurements and optical microscopic observations. Some HDAC inhibitors showed potent anthelmintic activities; three of them–entinostat, TH65, and TH92 –had pronounced anthelmintic effects, reducing parasite viability by ~100% at concentrations of ≤ 20 μM. These compounds were selected for further characterization and showed anthelmintic effects in the micromolar range and in a time- and dose-dependent manner. Moreover, these compounds induced major alterations on the morphology and ultrastructural features of M. vogae. The potencies of these compounds were higher than albendazole and the anthelmintic effects were irreversible. Additionally, we evaluated pairwise drug combinations of these HDAC inhibitors and albendazole. The results suggested a positive interaction in the anthelmintic effect for individual pairs of compounds. Due to the maximum dose approved for entinostat, adjustments in the dose regime and/or combinations with currently-used anthelmintic drugs are needed, and the selectivity of TH65 and TH92 towards parasite targets should be assessed.

Conclusion, significance

The results presented here suggest that HDAC inhibitors represent novel and potent drug candidates against cestodes and pave the way to understanding the roles of HDACs in these parasites.

<i>Schistosoma mansoni</i> alter transcription of immunomodulatory gene products following <i>in vivo</i> praziquantel exposure

PLoS Neglected Tropical Diseases News - 3 March 2021 - 2:00pm

by Paul McCusker, Claudia M. Rohr, John D. Chan

Control of the neglected tropical disease schistosomiasis relies almost entirely on praziquantel (PZQ) monotherapy. How PZQ clears parasite infections remains poorly understood. Many studies have examined the effects of PZQ on worms cultured in vitro, observing outcomes such as muscle contraction. However, conditions worms are exposed to in vivo may vary considerably from in vitro experiments given the short half-life of PZQ and the importance of host immune system engagement for drug efficacy in animal models. Here, we investigated the effects of in vivo PZQ exposure on Schistosoma mansoni. Measurement of pro-apoptotic caspase activation revealed that worm death occurs only after parasites shift from the mesenteric vasculature to the liver, peaking 24 hours after drug treatment. This indicates that PZQ is not directly schistocidal, since PZQ’s half-life is ~2 hours in humans and ~30 minutes in mice, and focuses attention on parasite interactions with the host immune system following the shift of worms to the liver. RNA-Seq of worms harvested from mouse livers following sub-lethal PZQ treatment revealed drug-evoked changes in the expression of putative immunomodulatory and anticoagulant gene products. Several of these gene products localized to the schistosome esophagus and may be secreted into the host circulation. These include several Kunitz-type protease inhibitors, which are also found in the secretomes of other blood feeding animals. These transcriptional changes may reflect mechanisms of parasite immune-evasion in response to chemotherapy, given the role of complement-mediated attack and the host innate/humoral immune response in parasite elimination. One of these isoforms, SmKI-1, has been shown to exhibit immunomodulatory and anti-coagulant properties. These data provide insight into the effect of in vivo PZQ exposure on S. mansoni, and the transcriptional response of parasites to the stress of chemotherapy.

Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells

PLoS Neglected Tropical Diseases News - 3 March 2021 - 2:00pm

by Pei Xu, Junling Gao, Chao Shan, Tiffany J. Dunn, Xuping Xie, Hongjie Xia, Jing Zou, Beatriz H. Thames, Amulya Sajja, Yongjia Yu, Alexander N. Freiberg, Nikos Vasilakis, Pei-Yong Shi, Scott C. Weaver, Ping Wu

Global Zika virus (ZIKV) outbreaks and their strong link to microcephaly have raised major public health concerns. ZIKV has been reported to affect the innate immune responses in neural stem/progenitor cells (NS/PCs). However, it is unclear how these immune factors affect neurogenesis. In this study, we used Asian-American lineage ZIKV strain PRVABC59 to infect primary human NS/PCs originally derived from fetal brains. We found that ZIKV overactivated key molecules in the innate immune pathways to impair neurogenesis in a cell stage-dependent manner. Inhibiting the overactivated innate immune responses ameliorated ZIKV-induced neurogenesis reduction. This study thus suggests that orchestrating the host innate immune responses in NS/PCs after ZIKV infection could be promising therapeutic approach to attenuate ZIKV-associated neuropathology.

Mapping suitability for Buruli ulcer at fine spatial scales across Africa: A modelling study

PLoS Neglected Tropical Diseases News - 3 March 2021 - 2:00pm

by Hope Simpson, Earnest Njih Tabah, Richard O. Phillips, Michael Frimpong, Issaka Maman, Edwin Ampadu, Joseph Timothy, Paul Saunderson, Rachel L. Pullan, Jorge Cano

Buruli ulcer (BU) is a disabling and stigmatising neglected tropical disease (NTD). Its distribution and burden are unknown because of underdiagnosis and underreporting. It is caused by Mycobacterium ulcerans, an environmental pathogen whose environmental niche and transmission routes are not fully understood. The main control strategy is active surveillance to promote early treatment and thus limit morbidity, but these activities are mostly restricted to well-known endemic areas. A better understanding of environmental suitability for the bacterium and disease could inform targeted surveillance, and advance understanding of the ecology and burden of BU. We used previously compiled point-level datasets of BU and M. ulcerans occurrence, evidence for BU occurrence within national and sub-national areas, and a suite of relevant environmental covariates in a distribution modelling framework. We fitted relationships between BU and M. ulcerans occurrence and environmental predictors by applying regression and machine learning based algorithms, combined in an ensemble model to characterise the optimal ecological niche for the disease and bacterium across Africa at a resolution of 5km x 5km. Proximity to waterbodies was the strongest predictor of suitability for BU, followed potential evapotranspiration. The strongest predictors of suitability for M. ulcerans were deforestation and potential evapotranspiration. We identified patchy foci of suitability throughout West and Central Africa, including areas with no previous evidence of the disease. Predicted suitability for M. ulcerans was wider but overlapping with that of BU. The estimated population living in areas predicted suitable for the bacterium and disease was 46.1 million. These maps could be used to inform burden estimations and case searches which would generate a more complete understanding of the spatial distribution of BU in Africa, and may guide control programmes to identify cases beyond the well-known endemic areas.

Household rat infestation in urban slum populations: Development and validation of a predictive score for leptospirosis

PLoS Neglected Tropical Diseases News - 3 March 2021 - 2:00pm

by Federico Costa, Caio Graco Zeppelini, Guilherme S. Ribeiro, Norlan Santos, Renato Barbosa Reis, Ridalva D. Martins, Deborah Bittencourt, Carlos Santana, Jonas Brant, Mitermayer G. Reis, Albert I. Ko

Domestic rats are the principal reservoir for urban leptospirosis. However, few studies have identified infestation markers in slums and evaluated their predictivity for leptospirosis risk. We compared households with leptospirosis cases in Salvador, Brazil between 2007 and 2009 and their neighbors using a case control design, surveying for rodent infestation signs and environmental characteristics. With the 2007–2008 data, a conditional logistic regression modeling identified the peridomiciliar presence of rodent burrows (OR, 3.30; 95% CI, 1.50–7.26), rat feces (2.86; 1.24–6.59), runs (2.57; 1.06–6.22), households bordering abandoned houses (2.48; 1.04–6.02), and unplastered walls (2.22; 1.02–6.02) as risk factors and developed a predictive score for leptospirosis. With an independent data set from 2009, a receiver operating characteristic (ROC) curve analysis evaluated the prediction score performance, with the area under the curve being 0.70 (95% CI, 0.64–0.76) for score development and 0.71 (0.65–0.79) for validation. Results indicate that high proportions of urban slum households are infested with R. norvegicus. The score performed well when identifying high-risk households within slums. These findings need confirmation in other urban centers, but suggest that community-based screening for rodent infestation can allow to target rodent and environmental control measures in populations at highest risk for leptospirosis.

Therapeutic advances in the topical treatment of cutaneous leishmaniasis: A review

PLoS Neglected Tropical Diseases News - 3 March 2021 - 2:00pm

by Marium Azim, Saeed Ahmad Khan, Saleem Ullah, Shafiq Ullah, Syed Ishtiaq Anjum

Cutaneous leishmaniasis has been endemic since decades. Millions of cases are reported worldwide specially in developing and underdeveloped countries. There are 2 major types of cutaneous leishmaniasis based on the causating species found in different regions of the world. These include New and Old World cutaneous leishmaniasis, which are self-healing, but if not treated, these may cause severe scars and many other complications like mucosal involvement. The conventional gold standard treatment for both types is mainly intralesional or parenteral administration of antimonial. Lately, a great deal of research has been done on development of topical treatment based on single agent or combination therapy. This review summarizes the current state of literature regarding therapeutic outcome of topical treatment against cutaneous leishmaniasis caused by different species in different regions.

Reassessment of the risk of birth defects due to Zika virus in Guadeloupe, 2016

PLoS Neglected Tropical Diseases News - 3 March 2021 - 2:00pm

by Anna L. Funk, Bruno Hoen, Ingrid Vingdassalom, Catherine Ryan, Philippe Kadhel, Kinda Schepers, Stanie Gaete, Benoit Tressières, Arnaud Fontanet

Background

In the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was 7.0% (95%CI: 5.0 to 9.5) among foetuses/infants of 546 women with symptomatic RT-PCR confirmed ZIKV infection during pregnancy. Many of these defects were isolated measurement-based microcephaly (i.e. without any detected brain or clinical abnormalities) or mild neurological conditions. We wanted to estimate the proportion of such minor findings among live births of women who were pregnant in the same region during the outbreak period but who were not infected with ZIKV.

Methods

In Guadeloupe, pregnant women were recruited at the time of delivery and tested for ZIKV infection. The outcomes of live born infants of ZIKV non-infected women were compared to those of ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA prospective cohort.

Results

Of 490 live born infants without exposure to ZIKV, 42 infants (8.6%, 95%CI: 6.2–11.4) had mild abnormalities that have been described as ‘potentially linked to ZIKV infection’; all but one of these was isolated measurement-based microcephaly. Among the 241 live born infants with ZIKV exposure, the proportion of such abnormalities, using the same definition, was similar (6.6%, 95%CI: 3.8–10.6).

Conclusions

Isolated anthropometric abnormalities and mild neurological conditions were as prevalent among infants with and without in-utero ZIKV exposure. If such abnormalities had not been considered as ‘potentially linked to ZIKV’ in the original prospective cohort in Guadeloupe, the overall estimate of the risk of birth defects considered due to the virus would have been significantly lower, at approximately 1.6% (95% CI: 0.4–4.1).

Trial registration

ClinicalTrials.gov (NCT02916732)

A multicenter, community-based, mixed methods assessment of the acceptability of a triple drug regimen for elimination of lymphatic filariasis

PLoS Neglected Tropical Diseases News - 3 March 2021 - 2:00pm

by Alison Krentel, Nandha Basker, Madsen Beau de Rochars, Joshua Bogus, Daniel Dilliott, Abdel N. Direny, Christine Dubray, Peter U. Fischer, Adriani Lomi Ga, Charles W. Goss, Myra Hardy, Cade Howard, Purushothaman Jambulingam, Christopher L. King, Moses Laman, Jean Frantz Lemoine, Shruti Mallya, Leanne J. Robinson, Josaia Samuela, Ken B. Schechtman, Andrew C. Steer, Taniawati Supali, Livingstone Tavul, Gary J. Weil

Background

Many countries will not reach elimination targets for lymphatic filariasis in 2020 using the two-drug treatment regimen (diethylcarbamazine citrate [DEC] and albendazole [DA]). A cluster-randomized, community-based safety study performed in Fiji, Haiti, India, Indonesia and Papua New Guinea tested the safety and efficacy of a new regimen of ivermectin, DEC and albendazole (IDA).

Methodology/Principal findings

To assess acceptability of IDA and DA, a mixed methods study was embedded within this community-based safety study. The study objective was to assess the acceptability of IDA versus DA. Community surveys were performed in each country with randomly selected participants (>14 years) from the safety study participant list in both DA and IDA arms. In depth interviews (IDI) and focus group discussions (FGD) assessed acceptability-related themes. In 1919 individuals, distribution of sex, microfilariae (Mf) presence and circulating filarial antigenemia (CFA), adverse events (AE) and age were similar across arms. A composite acceptability score summed the values from nine indicators (range 9–36). The median (22.5) score indicated threshold of acceptability. There was no difference in scores for IDA and DA regimens. Mean acceptability scores across both treatment arms were: Fiji 33.7 (95% CI: 33.1–34.3); Papua New Guinea 32.9 (95% CI: 31.9–33.8); Indonesia 30.6 (95% CI: 29.8–31.3); Haiti 28.6 (95% CI: 27.8–29.4); India 26.8 (95% CI: 25.6–28) (P<0.001). AE, Mf or CFA were not associated with acceptability. Qualitative research (27 FGD; 42 IDI) highlighted professionalism and appreciation for AE support. No major concerns were detected about number of tablets. Increased uptake of LF treatment by individuals who had never complied with MDA was observed.

Conclusions/Significance

IDA and DA regimens for LF elimination were highly and equally acceptable in individuals participating in the community-based safety study in Fiji, Haiti, India, Indonesia, and Papua New Guinea. Country variation in acceptability was significant. Acceptability of the professionalism of the treatment delivery was highlighted.

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