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Comparative analysis of time-based and quadrat sampling in seasonal population dynamics of intermediate hosts of human schistosomes

PLoS Neglected Tropical Diseases News - 20 December 2019 - 10:00pm

by Javier Perez-Saez, Théophile Mande, Dramane Zongo, Andrea Rinaldo

Background

Despite their importance for designing and evaluating schistosomiasis control trials, little attention in the literature has been dedicated to sampling protocols for the parasite’s snail intermediate hosts since their first development. We propose a comparative analysis of time-based and quadrat sampling protocols to quantify the seasonal variations in the abundance of these aquatic snail species of medical importance.

Methodology/Principal findings

Snail populations were monitored during 42 consecutive months in three types of habitats (ephemeral pond, ephemeral river and permanent stream) in two sites covering different climatic zones in Burkina Faso. We employed both a widely used time-based protocol of 30min of systematic collection at a weekly interval, and a quadrat protocol of 8 replicates per sample at a monthly interval. The correspondence between the two protocols was evaluated using an ensemble of statistical models including linear and saturating-type functional forms as well as allowing for count zero-inflation. The quadrat protocol yielded on average a relative standard error of 40%, for a mean snail density of 16.7 snails/m2 and index of dispersion of 1.51. Both protocols yielded similar seasonal patterns in snail abundance, confirming the asynchrony between permanent and ephemeral habitats with respect to the country’s seasonal rainfall patterns. Formal model comparison of the link between time vs. quadrat counts showed strong support of saturation for the latter and measurement zero-inflation, providing important evidence for the presence of density feedbacks in the snail’s population dynamics, as well as for spatial clustering.

Conclusions/Significance

In addition to the agreement with the time-based method, quadrat sampling provided insight into snail population dynamics and comparable density estimates across sites. The re-evaluation of these “traditional” sampling protocols, as well as the correspondence between their outputs, is of practical importance for the design and evaluation of schistosomiasis control trials.

Use of rapid diagnostic tests (RDTs) for conclusive diagnosis of chronic Chagas disease – field implementation in the Bolivian Chaco region

PLoS Neglected Tropical Diseases News - 19 December 2019 - 10:00pm

by Daniel Lozano, Lizeth Rojas, Susana Méndez, Aina Casellas, Sergi Sanz, Lourdes Ortiz, María Jesús Pinazo, Marcelo Abril, Joaquim Gascón, Faustino Torrico, Julio Alonso-Padilla

Chagas disease, caused by the parasite Trypanosoma cruzi, is the neglected tropical disease with a highest burden in Latin America. Its acute stage is mostly asymptomatic and goes unnoticed. Symptoms appear at the chronic stage, which is when diagnosis is usually made. This is based on the agreement of two conventional serological tests such as Enzyme-Linked Immunosorbent Assays (ELISAs). There are commercial kits with good sensitivity and specificity but their use is impractical in many highly endemic regions with poorly equipped laboratories. Luckily, several rapid diagnostic tests (RDTs) are available for the detection of anti-T. cruzi immunoglobulins. They are easy to operate, require no cold storage, provide fast turnaround of results, and some can work with a tiny volume of whole blood as sample. With the aim to field validate their use we compared an alternative algorithm based on a combination of RDTs with the standard based on ELISAs. In both cases a third test was available in case of discordance. RDTs were implemented by mobile teams in field campaigns to detect chronic T. cruzi-infections in the Chaco region of Bolivia. ELISAs were made in the reference laboratories located in the main hospitals of Yacuiba and Villa Montes, two major cities of the region. We enrolled 685 subjects who voluntarily participated in the study and had not been treated against the disease before. The agreement between the two main RDTs was 93.1% (638/685) (kappa index = 0.86; CI 95% 0.83–0.90). In comparison to the ELISAs algorithm, the combined use of the RDTs provided a sensitivity of 97.7% and a specificity of 96.1%. These results support the use of RDTs for the diagnosis of chronic Chagas disease in the studied region, and encourage their evaluation in other regions of Bolivia and other endemic countries.

Premature deaths by visceral leishmaniasis in Brazil investigated through a cohort study: A challenging opportunity?

PLoS Neglected Tropical Diseases News - 19 December 2019 - 10:00pm

by Ana Nilce S. Maia-Elkhoury, Gustavo Adolfo Sierra Romero, Samantha Y. O. B. Valadas, Marcia L. Sousa-Gomes, José Angelo Lauletta Lindoso, Elisa Cupolillo, Jose Antonio Ruiz-Postigo, Daniel Argaw, Manuel J. Sanchez-Vazquez

Background

Visceral Leishmaniasis (VL) is the most severe form of leishmaniasis because it can lead to death. In the Americas, 96% of cases are in Brazil, and despite efforts, the fatality rate has increased in the past years. We analyzed deaths associated to VL in Brazil and investigated the factors that could influence on the timeliness of fatal outcome with emphasis on time (tStoD).

Methodology

The registered deaths by VL were sourced from the Brazilian National Notification System from 2007–2014. Through a retrospective cohort study, univariate and multivariable Cox proportional hazards model analysis were performed and investigated the factors that could influence the time (tStoD). These factors were analyzed through survival models.

Results

Out of the 1,589 reported deaths, the median for onset of the symptoms and the case notification date (tStoN) is 25 days (10–61), and for date of case notification and death (tNotD) is 9 days (4–17). The time (tStoN) to event investigation for HIV non-infected individuals was 1.4 (1.16–1.68) greater than the HIV positive group. At the same time peri-urban and urban area were 0.83 (0.47–1.44) and 1.33 (1.16–1.52), respectively. The explorations revealed apparent differences between the time to event investigation (both for tStoN and tNotD) and the age at the onset of the symptoms. According to the tStoN the rate of notification is 1.73 times greater in patients under 5 years old at the onset of the clinical symptoms compared to older patients.

Conclusion

VL patients under 5 years old were diagnosed earlier and had shorter survival. It could mean that in younger population, although properly diagnosed, the fatality pattern might be related to the severity of the disease. Main host characteristics were evaluated, and age and co-infections seem to have an impact in the disease progression.

Gene drives for schistosomiasis transmission control

PLoS Neglected Tropical Diseases News - 19 December 2019 - 10:00pm

by Theresa Maier, Nicolas James Wheeler, Erica K. O. Namigai, Josh Tycko, Richard Ernest Grewelle, Yimtubezinash Woldeamanuel, Katharina Klohe, Javier Perez-Saez, Susanne H. Sokolow, Giulio A. De Leo, Timothy P. Yoshino, Mostafa Zamanian, Jutta Reinhard-Rupp

Schistosomiasis is one of the most important and widespread neglected tropical diseases (NTD), with over 200 million people infected in more than 70 countries; the disease has nearly 800 million people at risk in endemic areas. Although mass drug administration is a cost-effective approach to reduce occurrence, extent, and severity of the disease, it does not provide protection to subsequent reinfection. Interventions that target the parasites’ intermediate snail hosts are a crucial part of the integrated strategy required to move toward disease elimination. The recent revolution in gene drive technology naturally leads to questions about whether gene drives could be used to efficiently spread schistosome resistance traits in a population of snails and whether gene drives have the potential to contribute to reduced disease transmission in the long run. Responsible implementation of gene drives will require solutions to complex challenges spanning multiple disciplines, from biology to policy. This Review Article presents collected perspectives from practitioners of global health, genome engineering, epidemiology, and snail/schistosome biology and outlines strategies for responsible gene drive technology development, impact measurements of gene drives for schistosomiasis control, and gene drive governance. Success in this arena is a function of many factors, including gene-editing specificity and efficiency, the level of resistance conferred by the gene drive, how fast gene drives may spread in a metapopulation over a complex landscape, ecological sustainability, social equity, and, ultimately, the reduction of infection prevalence in humans. With combined efforts from across the broad global health community, gene drives for schistosomiasis control could fortify our defenses against this devastating disease in the future.

Seroprevalence estimates for toxocariasis in people worldwide: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 19 December 2019 - 10:00pm

by Ali Rostami, Seyed Mohammad Riahi, Celia V. Holland, Ali Taghipour, Mohsen Khalili-Fomeshi, Yadolah Fakhri, Vahid Fallah Omrani, Peter J. Hotez, Robin B. Gasser

Background

Human toxocariasis is an important neglected disease. We performed a systematic review and meta-analysis study to estimate the global and regional prevalence of anti-Toxocara serum antibodies (referred to as ‘T-seroprevalence’) in human populations around the world.

Methods

We searched five international databases (PubMed, EMBASE, Web of Science, SciELO and Scopus) for seroprevalence studies published from 1 January 1980 to 15 March 2019. We used random effect models to calculate the overall T-seroprevalence (with 95% CIs) in all six WHO regions and worldwide. We also conducted subgroup and linear meta-regression analyses to evaluate the impact of socio-demographic, geographical and climatic parameters on seroprevalence.

Results

We identified 250 eligible studies (253 datasets) comprising 265,327 participants in 71 countries for inclusion in the present meta-analysis. The estimated global T-seroprevalence rate was 19.0% (95%CI, 16.6–21.4%; 62,927/265,327); seroprevalence was highest in the African region (37.7%; 25.7–50.6%) and lowest in the Eastern Mediterranean region (8.2%; 5.1–12.0%). The pooled seroprevalence for other WHO regions was 34.1% (20.2–49.4%) in the South-East Asia; 24.2% (16.0–33.5%) in the Western Pacific; 22.8% (19.7–26.0%) in the American; and 10.5% (8.5–12.8%) in the European regions. A significantly higher T-seroprevalence was associated with a lower income level; lower human development index (HDI); lower latitude; higher humidity; higher temperature; and higher precipitation (P-value < 0.001). Potential risk factors associated with seropositivity to Toxocara included male gender; living in a rural area; young age; close contact with dogs, cats or soil; consumption of raw meat; and the drinking of untreated water.

Conclusions

The present findings indicate high levels of infection with, or exposure to Toxocara spp. in many countries, which calls for increased attention to human toxocariasis and improved measures to prevent adverse health risks of this disease.

The Joint Mobile Emerging Disease Clinical Capability (JMEDICC) laboratory approach: Capabilities for high-consequence pathogen clinical research

PLoS Neglected Tropical Diseases News - 19 December 2019 - 10:00pm

by Prossy Naluyima, Willy Kayondo, Chi Ritchie, Joseph Wandege, Sharon Kagabane, Lydia Tumubeere, Brenda Kusiima, Daniel Kibombo, Sharon Atukunda, Christine Nanteza, Harriet Nabirye, Francis Bunjo Mugabi, Sarah Namuyanja, Christopher Hatcher, Hypaitia Rauch, Moses Mukembo, Patrick Musinguzi, JMEDICC Consortium , Nathan Sanders, Elizabeth Turesson, Christian Cando, Richard Walwema, Derrick Mimbe, Janice Hepburn, Danielle Clark, Mohammed Lamorde, Hannah Kibuuka, Saima Zaman, Anthony P. Cardile, Karen A. Martins

Following the 2013–2016 Ebola virus outbreak in West Africa, numerous groups advocated for the importance of executing clinical trials in outbreak settings. The difficulties associated with obtaining reliable data to support regulatory approval of investigational vaccines and therapeutics during that outbreak were a disappointment on a research and product development level, as well as on a humanitarian level. In response to lessons learned from the outbreak, the United States Department of Defense established a multi-institute project called the Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC). JMEDICC’s primary objective is to establish the technical capability in western Uganda to execute clinical trials during outbreaks of high-consequence pathogens such as the Ebola virus. A critical component of clinical trial execution is the establishment of laboratory operations. Technical, logistical, and political challenges complicate laboratory operations, and these challenges have been mitigated by JMEDICC to enable readiness for laboratory outbreak response operations.

A BONCAT-iTRAQ method enables temporally resolved quantitative profiling of newly synthesised proteins in <i>Leishmania mexicana</i> parasites during starvation

PLoS Neglected Tropical Diseases News - 19 December 2019 - 10:00pm

by Karunakaran Kalesh, Paul W. Denny

Adaptation to starvation is integral to the Leishmania life cycle. The parasite can survive prolonged periods of nutrient deprivation both in vitro and in vivo. The identification of parasite proteins synthesised during starvation is key to unravelling the underlying molecular mechanisms facilitating adaptation to these conditions. Additionally, as stress adaptation mechanisms in Leishmania are linked to virulence as well as infectivity, profiling of the complete repertoire of Newly Synthesised Proteins (NSPs) under starvation is important for drug target discovery. However, differential identification and quantitation of low abundance, starvation-specific NSPs from the larger background of the pre-existing parasite proteome has proven difficult, as this demands a highly selective and sensitive methodology. Herein we introduce an integrated chemical proteomics method in L. mexicana promastigotes that involves a powerful combination of the BONCAT technique and iTRAQ quantitative proteomics Mass Spectrometry (MS), which enabled temporally resolved quantitative profiling of de novo protein synthesis in the starving parasite. Uniquely, this approach integrates the high specificity of the BONCAT technique for the NSPs, with the high sensitivity and multiplexed quantitation capability of the iTRAQ proteomics MS. Proof-of-concept experiments identified over 250 starvation-responsive NSPs in the parasite. Our results show a starvation-specific increased relative abundance of several translation regulating and stress-responsive proteins in the parasite. GO analysis of the identified NSPs for Biological Process revealed translation (enrichment P value 2.47e-35) and peptide biosynthetic process (enrichment P value 4.84e-35) as extremely significantly enriched terms indicating the high specificity of the NSP towards regulation of protein synthesis. We believe that this approach will find widespread use in the study of the developmental stages of Leishmania species and in the broader field of protozoan biology.

HTLV-1 proviral load in infective dermatitis associated with HTLV-1 does not increase after the development of HTLV-1-associated myelopathy/tropical spastic paraparesis and does not decrease after IDH remission

PLoS Neglected Tropical Diseases News - 18 December 2019 - 10:00pm

by Everton S. Batista, Pedro D. Oliveira, Janeusa Primo, Cinthya Maria Neves Varandas, Ana Paula Nunes, Achiléa L. Bittencourt, Lourdes Farre

Introduction

Infective dermatitis associated with HTLV-1 (IDH) is a recurrent eczema which affects children vertically infected with HTLV-1. In Bahia, Brazil, we recently reported that 47% of IDH patients also develop juvenile HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive disabling disorder which is typically reported in adult HTLV-1 carriers. IDH may also predispose to adult T-cell leukemia/lymphoma, a neoplasm associated with HTLV-1. The factors relating to the development of HTLV-1-associated juvenile diseases have not yet been defined. HTLV-1 proviral load (PVL) is one of the main parameters related to the development of HTLV-1 associated diseases in adults. In the current study, we investigated the role of PVL in IDH and juvenile HAM/TSP.

Methodology/Principal findings

This is a cohort study that included fifty-nine HTLV-1 infected children and adolescents, comprising 16 asymptomatic carriers, 18 IDH patients, 20 patients with IDH and HAM/TSP (IDH/HAM/TSP) and five with HAM/TSP. These patients were followed-up for up to 14 years (median of 8 years). We found that PVL in IDH and IDH/HAM/TSP patients were similarly higher than PVL in juvenile asymptomatic carriers (p<0.0001). In those IDH patients who developed HAM/TSP during follow-up, PVL levels did not vary significantly. HAM/TSP development did not occur in those IDH patients who presented high levels of PVL. IDH remission was associated with an increase of PVL. Inter-individual differences in PVL were observed within all groups. However, intra-individual PVL did not fluctuate significantly during follow-up.

Conclusions/Significance

High PVL in IDH patients was not necessary indicative of progression to HAM/TSP. PVL did not decrease after IDH remission. The maintenance of high PVL after remission could favor early development of ATL. Therefore, IDH patients would have to be followed-up even after remission of IDH and for a long period of time.

The role of the first level of health care in the approach to Chagas disease in a non-endemic country

PLoS Neglected Tropical Diseases News - 16 December 2019 - 10:00pm

by Laura Iglesias-Rus, María Romay-Barja, Teresa Boquete, Agustín Benito, Teresa Blasco-Hernández

Background

Chagas disease has crossed South America’s borders and in recent years has spread to regions that were not previously affected. Early diagnosis and treatment of Chagas disease improves the clinical prognosis and prevents vertical transmission. Taking into account the lack of evidence of how primary care services manage Chagas disease in a non-endemic country, this study assessed Chagas disease knowledge, attitudes and practices among primary health care professionals.

Methods and principal findings

Between 2017 and 2019, eight focus groups were formed with 41 family physicians and 40 nurses from healthcare centers in Madrid, Spain, and 70 field notes were collected during non-participant observation. The family physicians and nurses showed a lack of general knowledge about Chagas disease, and they did not identify the country of origin to request the blood test. The family physicians and nurses thought that the population did not talk broadly about Chagas disease because of the stigma or shame. The role of nurses was more focused on vaccination status and chronic disease follow-up, and family physicians assumed a facilitating role to send patients to different hospital facilities. Communication between primary care professionals and the hospital is a barrier frequently experienced by family physicians.

Conclusions

The diagnosis of CD in non-endemic countries continues being an important challenge for health systems. The results obtained with the study of the knowledge, attitudes and practices at primary care through a qualitative approach allows to obtain evidence that could help to develop strategies for the screening of CD in a protocolized way in order to avoid that the diagnosis depends exclusively on the request of the patient.

Coverage assessment survey following trachoma mass drug administration (MDA) in six districts of Oromia, Western Ethiopia, 2017

PLoS Neglected Tropical Diseases News - 16 December 2019 - 10:00pm

by Tariku Tesfaye Bekuma, Getu Mosisa Kebebew, Zelalem Desalegn Waktole, Jote Markos Cafo, Desalegn Wirtu, Solomon Gaddisa

Background

Trachoma is a contagious infection of the eye by specific strains of the bacteria Chlamydia trachomatis. It is the leading cause of blindness worldwide. Mass drug administration (MDA) with azithromycin is a cornerstone of World Health Organization (WHO)’s global effort to eliminate trachoma by 2020. This coverage survey was aimed to assess trachoma post-mass drug administration (MDA) coverage among six selected districts of East Wollega, Horo Guduru Wollega, and West Shewa zones in2017.

Methods

A community based cross-sectional coverage survey was conducted. The sample size was calculated automatically using Coverage Survey Builder (CSB) tool in microsoft excel. Thirty segments were selected per each selected districts of the three zones. A separate Results Entry Form for each district surveyed was completed, saved and uploaded directly into the online Coverage Survey Analysis Tool to estimate the surveycoverage and the program reach along with the corresponding 95% confidence limits and design effects. EPI-INFO 7.0 and SPSS version 20 was used for further analysis of survey data.

Result

A total of 1,747 households were surveyed, out of which 10,700 individuals were interviewed. Most respondents (95.1%) stated that they heard about trachoma MDA and most of them replied that they got the information from health workers. Program reach ranged between 89.5% in Jimma Geneti district and 94.8% in Dirre Hinchini district. The most common mentioned reasons for not having taken azithromycin included not knowing about the campaign, fear of side effects and being absent during the MDA campaign.

Conclusion

In this survey, four of the six districts met the target threshold (i.e. 80%) for effective coverage; Ambo rural and Jimma Geneti did not meet the target threshold.Therefore, programmatic improvements should be made for the future campaign to reach the expected thresholds while the campaign in four of the six districts should be encouraged.

Identification and validation of specific B-cell epitopes of hantaviruses associated to hemorrhagic fever and renal syndrome

PLoS Neglected Tropical Diseases News - 16 December 2019 - 10:00pm

by Fernando de Paiva Conte, Bianca Corrêa Tinoco, Thiago Santos Chaves, Renata Carvalho de Oliveira, Janaina Figueira Mansur, Ronaldo Mohana-Borges, Elba Regina Sampaio de Lemos, Patricia Cristina da Costa Neves, Rodrigo Nunes Rodrigues-da-Silva

Background

Orthohantavirus infection is a neglected global health problem affecting approximately 200,000 people/year, spread by rodent hosts and associated to fatal human diseases, such as hemorrhagic fever with renal syndrome (HFRS) and orthohantavirus cardiopulmonary syndrome (HCPS). Circulation of HFRS-associated orthohantaviruses, such as Seoul, Gou, Amur, Dobrava and Hantaan, are supposed to be restricted to Eurasian countries even though their hosts can be a worldwide distribution. Few confirmed HFRS orthohantavirus infections in humans have been reported in American countries, but due to lower medical awareness of the symptoms of this zoonosis, it could be associated to viral underreporting or to misdiagnosis with several tropical hemorrhagic diseases. Serological evidence of orthohantavirus infections, using enzyme-linked immunosorbent assay for the presence of immunoglobulin M and G against recombinant nucleoprotein protein, remains as an essential assay for viral surveillance. In this study, we aimed to identify in silico immunogenic B-cell linear epitopes present on orthohantavirus nucleoprotein that are exclusive to HFRS-related species.

Methodology/Principal findings

In silico analysis were performed using Seoul orthohantavirus nucleoprotein (SHNP) sequence as a model. Linear B-cell-epitopes on SHNP and its immunogenicity were predicted by BepiPred-2.0 and Vaxijen algorithms, respectively. The conservancy of predicted epitopes was compared with the most clinically relevant HFRS or HCPS-associated orthohantavirus, aiming to identify specific sequences from HFRS-orthohantavirus. Peptide validation was carried out by ELISA using Balb/c mice sera immunized with purified recombinant rSHNP. Peptides cross-reactivity against HCPS orthohantavirus were evaluated using immunized sera from mice injected with recombinant Juquitiba orthohantavirus nucleoprotein (rJHNP).

Conclusion/Significance

In silico analysis revealed nine potential immunogenic linear B-cell epitopes from SHNP; among them, SHNP(G72-D110) and SHNP(P251-D264) showed a high degree of sequence conservation among HFRS-related orthohantavirus and were experimentally validated against rSHNP-IMS and negatively validated against rJHNP-IMS. Taken together, we identified and validated two potential antigenic B-cell epitopes on SHNP, which were conserved among HFRS-associated orthohantavirus and could be applied to the development of novel immunodiagnostic tools for orthohantavirus surveillance.

Human <i>Trypanosoma cruzi</i> infection is driven by eco-social interactions in rural communities of the Argentine Chaco

PLoS Neglected Tropical Diseases News - 16 December 2019 - 10:00pm

by Maria del Pilar Fernández, Maria Sol Gaspe, Paula Sartor, Ricardo E. Gürtler

The transmission of Trypanosoma cruzi to humans is determined by multiple ecological, socio-economic and cultural factors acting at different scales. Their effects on human infection with T. cruzi have often been examined separately or using a limited set of ecological and socio-demographic variables. Herein, we integrated the ecological and social dimensions of human infection risk with the spatial distribution patterns of human and vector (Triatoma infestans) infection in rural communities of the Argentine Chaco composed of indigenous people (90% Qom) and a creole minority. We conducted serosurveys in 470 households aiming at complete population enumeration over 2012–2015. The estimated seroprevalence of T. cruzi prior to the implementation of an insecticide spraying campaign (2008) was 29.0% (N = 1,373 in 301 households), and was twice as large in Qom than creoles. Using generalized linear mixed models, human seropositive cases significantly increased with infected triatomine abundance, having a seropositive household co-inhabitant and household social vulnerability (a multidimensional index of poverty), and significantly decreased with increasing host availability in sleeping quarters (an index summarizing the number of domestic hosts for T. infestans). Vulnerable household residents were exposed to a higher risk of infection even at low infected-vector abundances. The risk of being seropositive increased significantly with house infestation among children from stable households, whereas both variables were not significantly associated among children from households exhibiting high mobility within the communities, possibly owing to less consistent exposures. Human infection was clustered by household and at a larger spatial scale, with hotspots of human and vector infection matching areas of higher social vulnerability. These results were integrated in a risk map that shows high-priority areas for targeted interventions oriented to suppress house (re)infestations, detect and treat infected children, and thus reduce the burden of future disease.

Transcriptional responses of <i>Biomphalaria pfeifferi</i> and <i>Schistosoma mansoni</i> following exposure to niclosamide, with evidence for a synergistic effect on snails following exposure to both stressors

PLoS Neglected Tropical Diseases News - 16 December 2019 - 10:00pm

by Sarah K. Buddenborg, Bishoy Kamel, Lijing Bu, Si-Ming Zhang, Gerald M. Mkoji, Eric S. Loker

Background

Schistosomiasis is one of the world’s most common NTDs. Successful control operations often target snail vectors with the molluscicide niclosamide. Little is known about how niclosamide affects snails, including for Biomphalaria pfeifferi, the most important vector for Schistosoma mansoni in Africa. We used Illumina technology to explore how field-derived B. pfeifferi, either uninfected or harboring cercariae–producing S. mansoni sporocysts, respond to a sublethal treatment of niclosamide. This study afforded the opportunity to determine if snails respond differently to biotic or abiotic stressors, and if they reserve unique responses for when presented with both stressors in combination. We also examined how sporocysts respond when their snail host is treated with niclosamide.

Principal findings

Cercariae-producing sporocysts within snails treated with niclosamide express ~68% of the genes in the S. mansoni genome, as compared to 66% expressed by intramolluscan stages of S. mansoni in snails not treated with niclosamide. Niclosamide does not disable sporocysts nor does it seem to provoke from them distinctive responses associated with detoxifying a xenobiotic. For uninfected B. pfeifferi, niclosamide treatment alone increases expression of several features not up-regulated in infected snails including particular cytochrome p450s and heat shock proteins, glutathione-S-transferases, antimicrobial factors like LBP/BPI and protease inhibitors, and also provokes strong down regulation of proteases. Exposure of infected snails to niclosamide resulted in numerous up-regulated responses associated with apoptosis along with down-regulated ribosomal and defense functions, indicative of a distinctive, compromised state not achieved with either stimulus alone.

Conclusions/Significance

This study helps define the transcriptomic responses of an important and under-studied schistosome vector to S. mansoni sporocysts, to niclosamide, and to both in combination. It suggests the response of S. mansoni sporocysts to niclosamide is minimal and not reflective of a distinct repertoire of genes to handle xenobiotics while in the snail host. It also offers new insights for how niclosamide affects snails.

Validity and reliability of telephone administration of the patient specific functional scale for the assessment of recovery from snakebite envenomation

PLoS Neglected Tropical Diseases News - 13 December 2019 - 10:00pm

by Rebecca G. Theophanous, Joao Ricardo Nickenig Vissoci, Fan Hui Wen, S. Michelle Griffin, Victoria E. Anderson, Michael E. Mullins, Nicklaus P. Brandehoff, Eugenia B. Quackenbush, Sean P. Bush, Eric A. Toschlog, Spencer C. Greene, Kapil Sharma, Kurt Kleinschmidt, Nathan P. Charlton, S. Rutherfoord Rose, Richard Schwartz, Brandon Lewis, Eric J. Lavonas, Charles J. Gerardo

Objectives

Although more than 1.8 million people survive snakebite envenomation each year, their recovery is understudied. Obtaining long-term follow-up is challenging in both high- and low-resource settings. The Patient-Specific Functional Scale (PSFS) is an easily administered, well-accepted patient-reported outcome that is validated for assessing limb recovery from snakebite envenomation. We studied whether the PSFS is valid and reliable when administered by telephone.

Methods

This is a secondary analysis of data from a randomized clinical trial. We analyzed the results of PSFS collected in-person on days 3, 7, 14, 21, and 28 and by telephone on days 10, 17, and 24. We assessed the following scale psychometric properties: (a) content validity (ceiling and floor effects), (b) internal structure and consistency (Cronbach’s alpha), and (c) temporal and external validity using Intraclass Correlation Coefficient (ICC). Temporal stability was assessed using Spearman’s correlation coefficient and agreement between adjacent in-person and telephonic assessments with Cohen’s kappa. Bland Altman analysis was used to assess differential bias in low and high score results.

Results

Data from 74 patients were available for analysis. Floor effects were seen in the early post-injury time points (median: 3 (IQR: 0, 5) at 3 days post-enrollment) and ceiling effects in the late time points (median: 9 (IQR: 8, 10). Internal consistency was good to excellent with both in-person (Cronbach α: 0.91 (95%CI 0.88, 0.95)) and telephone administration (0.81 (0.73, 0.89). Temporal stability was also good (ICC: 0.83 (0.72, 0.89) in-person, 0.80 (0.68, 0.88) telephone). A strong linear correlation was found between in-person and telephone administration (Spearman’s ρ: 0.83 (CI: 0.78, 0.84), consistency was assessed as excellent (Cohen’s κ 0.81 (CI: 0.78, 0.84), and Bland Altman analysis showed no systematic bias.

Conclusions

Telephone administration of the PSFS provides valid, reliable, and consistent data for the assessment of recovery from snakebite envenomation.

<i>Trypanosoma cruzi</i> transmission dynamics in a synanthropic and domesticated host community

PLoS Neglected Tropical Diseases News - 13 December 2019 - 10:00pm

by Alheli Flores-Ferrer, Etienne Waleckx, Guilhem Rascalou, Eric Dumonteil, Sébastien Gourbière

Trypanosoma cruzi is the causative agent of Chagas disease, a Neglected Tropical Disease affecting 8 million people in the Americas. Triatomine hematophagous vectors feed on a high diversity of vertebrate species that can be reservoirs or dead-end hosts, such as avian species refractory to T. cruzi. To understand its transmission dynamics in synanthropic and domesticated species living within villages is essential to quantify disease risk and assess the potential of zooprophylaxis. We developed a SI model of T. cruzi transmission in a multi-host community where vector reproduction and parasite transmission depend on a triatomine blood-feeding rate accounting for vector host preferences and interference while feeding. The model was parameterized to describe T. cruzi transmission in villages of the Yucatan peninsula, Mexico, using the information about Triatoma dimidiata vectors and host populations accumulated over the past 15 years. Extensive analyses of the model showed that dogs are key reservoirs and contributors to human infection, as compared to synanthropic rodents and cats, while chickens or other domesticated avian hosts dilute T. cruzi transmission despite increasing vector abundance. In this context, reducing the number of dogs or increasing avian hosts abundance decreases incidence in humans by up to 56% and 39%, respectively, while combining such changes reduces incidence by 71%. Although such effects are only reached over >10-years periods, they represent important considerations to be included in the design of cost-effective Integrated Vector Management. The concomitant reduction in T. cruzi vector prevalence estimated by simulating these zooprophylactic interventions could indeed complement the removal of colonies from the peridomiciles or the use of insect screens that lower vector indoor abundance by ~60% and ~80%. These new findings reinforce the idea that education and community empowerment to reduce basic risk factors is a cornerstone to reach and sustain the key objective of interrupting Chagas disease intra-domiciliary transmission.

Optimising targets for tsetse control: Taking a fly’s-eye-view to improve the colour of synthetic fabrics

PLoS Neglected Tropical Diseases News - 12 December 2019 - 10:00pm

by Roger D. Santer, Glyn A. Vale, David Tsikire, Steve J. Torr

The savannah tsetse flies, Glossina morsitans morsitans and G. pallidipes, are important vectors of Rhodesian human African trypanosomiasis and animal African trypanosomiasis in East and southern Africa. We tested in Zimbabwe whether robust, synthetic fabrics, and innovative fly’s-eye-view approaches to optimise fabric colour, can improve insecticide-treated targets employed for tsetse control. Flies were caught by electrocution at a standard target comprising a 1m x 1m black cotton cloth panel with 1m x 0.5m black polyester net panels on each side. Catches were subdivided by species and sex. Tsetse catches were unaffected by substitution of the black cotton with a blue polyester produced for riverine tsetse targets. Exchanging the net panels for phthalogen blue cotton to simulate the target routinely used in Zimbabwe significantly reduced catches of female G. m. morsitans (mean catch 0.7 times that at standard), with no effect on other tsetse catches. However, significantly greater proportions of the catch were intercepted at the central panel of the Zimbabwe (means 0.47–0.79) versus standard designs (0.11–0.29). We also engineered a new violet polyester cloth using models of tsetse attraction based upon fly photoreceptor responses. With and without odour lure, catches of females of both species at the violet target were significantly greater than those at standard (means 1.5–1.6 times those at standard), and typical blue polyester targets (means 0.9–1.3 times those at standard). Similar effects were observed for males under some combinations of species and odour treatment. The proportions of catch intercepted at the central panel of the violet target (means 0.08–0.18) were intermediate between those at standard and typical blue polyester. Further, the reflectance spectrum of violet polyester was more stable under field conditions than that of black cotton. Our results demonstrate the effectiveness of photoreceptor-based models as a novel means of improving targets to control tsetse and trypanosomiases.

Genomes of <i>Leishmania</i> parasites directly sequenced from patients with visceral leishmaniasis in the Indian subcontinent

PLoS Neglected Tropical Diseases News - 12 December 2019 - 10:00pm

by Malgorzata A. Domagalska, Hideo Imamura, Mandy Sanders, Frederik Van den Broeck, Narayan Raj Bhattarai, Manu Vanaerschot, Ilse Maes, Erika D’Haenens, Keshav Rai, Suman Rijal, Matthew Berriman, James A. Cotton, Jean-Claude Dujardin

Whole genome sequencing (WGS) is increasingly used for molecular diagnosis and epidemiology of infectious diseases. Current Leishmania genomic studies rely on DNA extracted from cultured parasites, which might introduce sampling and biological biases into the subsequent analyses. Up to now, direct analysis of Leishmania genome in clinical samples is hampered by high levels of human DNA and large variation in parasite load in clinical samples. Here, we present a method, based on target enrichment of Leishmania donovani DNA with Agilent SureSelect technology, that allows the analysis of Leishmania genomes directly in clinical samples. We validated our protocol with a set of artificially mixed samples, followed by the analysis of 63 clinical samples (bone marrow or spleen aspirates) from visceral leishmaniasis patients in Nepal. We were able to identify genotypes using a set of diagnostic SNPs in almost all of these samples (97%) and access comprehensive genome-wide information in most (83%). This allowed us to perform phylogenomic analysis, assess chromosome copy number and identify large copy number variants (CNVs). Pairwise comparisons between the parasite genomes in clinical samples and derived in vitro cultured promastigotes showed a lower aneuploidy in amastigotes as well as genomic differences, suggesting polyclonal infections in patients. Altogether our results underline the need for sequencing parasite genomes directly in the host samples

Distribution of insecticide resistance and mechanisms involved in the arbovirus vector <i>Aedes aegypti</i> in Laos and implication for vector control

PLoS Neglected Tropical Diseases News - 12 December 2019 - 10:00pm

by Sébastien Marcombe, Bénédicte Fustec, Julien Cattel, Somesanith Chonephetsarath, Phoutmany Thammavong, Nothasin Phommavanh, Jean-Philippe David, Vincent Corbel, Ian W. Sutherland, Jeffrey C. Hertz, Paul T. Brey

Background

The yellow fever mosquito Aedes aegypti is the major vector of dengue, yellow fever, Zika, and Chikungunya viruses. Worldwide vector control is largely based on insecticide treatments but, unfortunately, vector control programs are facing operational challenges due to mosquitoes becoming resistant to commonly used insecticides. In Southeast Asia, resistance of Ae. aegypti to chemical insecticides has been documented in several countries but no data regarding insecticide resistance has been reported in Laos. To fill this gap, we assessed the insecticide resistance of 11 Ae. aegypti populations to larvicides and adulticides used in public health operations in the country. We also investigated the underlying molecular mechanisms associated with resistance, including target site mutations and detoxification enzymes putatively involved in metabolic resistance.

Methods & results

Bioassays on adults and larvae collected in five provinces revealed various levels of resistance to organophosphates (malathion and temephos), organochlorine (DDT) and pyrethroids (permethrin and deltamethrin). Synergist bioassays showed a significant increased susceptibility of mosquitoes to insecticides after exposure to detoxification enzyme inhibitors. Biochemical assays confirmed these results by showing significant elevated activities of cytochrome P450 monooxygenases (P450), glutathione S-transferases (GST) and carboxylesterases (CCE) in adults. Two kdr mutations, V1016G and F1534C, were detected by qPCR at low and high frequency, respectively, in all populations tested. A significant negative association between the two kdr mutations was detected. No significant association between kdr mutations frequency (for both 1534C and 1016G) and survival rate to DDT or permethrin (P > 0.05) was detected. Gene Copy Number Variations (CNV) were detected for particular detoxification enzymes. At the population level, the presence of CNV affecting the carboxylesterase CCEAE3A and the two cytochrome P450 CYP6BB2 and CYP6P12 were significantly correlated to insecticide resistance.

Conclusions

These results suggest that both kdr mutations and metabolic resistance mechanisms are present in Laos but their impact on phenotypic resistance may differ in proportion at the population or individual level. Molecular analyses suggest that CNV affecting CCEAE3A previously associated with temephos resistance is also associated with malathion resistance while CNV affecting CYP6BB2 and CYP6P12 are associated with pyrethroid and possibly DDT resistance. The presence of high levels of insecticide resistance in the main arbovirus vector in Laos is worrying and may have important implications for dengue vector control in the country.

Gender-related factors affecting health seeking for neglected tropical diseases: findings from a qualitative study in Ethiopia

PLoS Neglected Tropical Diseases News - 12 December 2019 - 10:00pm

by Alexandra Wharton-Smith, Christian Rassi, Esey Batisso, Giuseppina Ortu, Rebecca King, Misganu Endriyas, Helen Counihan, Prudence Hamade, Dawit Getachew

Background

Despite known gender-specific differences in terms of prevalence, transmission and exposure to neglected tropical diseases (NTDs), there is limited discussion of the influence of gender in NTD programmes and interventions. There is a paucity of research on how gender interacts with NTD service provision and uptake. This study, part of broader implementation research in Ethiopia, applied a gender lens to health seeking for five NTDs: lymphatic filariasis, podoconiosis, schistosomiasis, soil-transmitted helminth infection and trachoma.

Methodology/principal findings

The study was conducted in a district of the Southern Nations, Nationalities, and Peoples' Region of Ethiopia where the five NTDs are prevalent. A qualitative methodology was adopted to explore participants’ perspectives and experiences. Data generation methods included 20 interviews and four focus group discussions. Community members, volunteer Health Development Army leaders, Health Extension Workers and a range of health workers at the health post, health centre and hospital level (n = 59) were purposively sampled. Interviews and focus group discussions were audio recorded, transcribed verbatim into English then analysed through open coding, drawing on constant comparative methods.Gender related factors affected care seeking for NTDs and were described as reasons for not seeking care, delayed care seeking and treating NTDs with natural remedies. Women faced additional challenges in seeking health care due to gender inequalities and power dynamics in their domestic partnerships. Participants recommended raising community awareness about NTDs, however this remains problematic due to gender and social norms around appropriate discourse with members of the opposite gender.

Conclusions/significance

The findings from this study provide crucial insights into how gender interacts with accessing health services, at different levels of the health system. If we are committed to leaving no one behind and achieving universal health coverage, it is essential to address gender disparities to access and utilisation of interventions delivered by national NTD programmes.

Cutaneous leishmaniasis in Syria: A review of available data during the war years: 2011–2018

PLoS Neglected Tropical Diseases News - 12 December 2019 - 10:00pm

by Ghada Muhjazi, Albis Francesco Gabrielli, José Antonio Ruiz-Postigo, Hoda Atta, Mona Osman, Hyam Bashour, Atef Al Tawil, Hania Husseiny, Rasmieh Allahham, Richard Allan

Background

Cutaneous leishmaniasis (CL) has historically been reported from Syria. Since 2011, the country has been affected by a war, which has impacted health and health services. Over the same period, an increase in the number of cases of CL has been reported from several areas across the country and by a number of authors. This study aims to provide the first quantitative evidence of the epidemiological evolution of CL in Syria during the war.

Materials and methods

Data on number of CL cases for the period 2011–2018 were extracted from three different surveillance systems: the Ministry of Health (MoH) routine surveillance system, the MoH/WHO sentinel-syndromic Early Warning Alert and Response System (EWARS), and surveillance data collected by the international nongovernmental organization (NGO) the MENTOR Initiative. Data were cleaned and merged to generate the best possible estimates on number of CL cases; incidence of CL was also calculated based on data on resident population. Data reported from the years preceding the conflict (2007–2010) were also added to the analysis for comparative purposes.

Results

The analysis of data from the three available sources over the period considered indicates that number of reported cases progressively grew from prewar levels to reach a peak in 2015, decreased in 2016, remained stable in 2017, and increased again in 2018. Such a trend was mirrored by changes in incidence of infection. Some governorates, which used to report low numbers of CL cases, started recording higher number of cases after the onset of the war.

Conclusion

The war coincided with a major rise in reported number of CL cases and incidence of infection, although an increasing trend was already appreciable before its onset.

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