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Development and evaluation of a rapid and simple diagnostic assay for COVID-19 based on loop-mediated isothermal amplification

PLoS Neglected Tropical Diseases News - 4 November 2020 - 10:00pm

by Rokusuke Yoshikawa, Haruka Abe, Yui Igasaki, Saeki Negishi, Hiroaki Goto, Jiro Yasuda

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic novel coronavirus that has caused a worldwide outbreak. Here we describe a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay that uses a portable device for efficient detection of SARS-CoV-2. This RT-LAMP assay specifically detected SARS-CoV-2 without cross-reacting with the most closely related human coronavirus, SARS-CoV. Clinical evaluation of nasal swab samples from suspected SARS-CoV-2 pneumonia (COVID-19) patients showed that the assay could detect over 23.7 copies within 15 min with a 100% probability. Since the RT-LAMP assay can be performed with a portable battery-supported device, it is a rapid, simple, and sensitive diagnostic assay for COVID-19 that can be available at point-of-care. We also developed the RT-LAMP assay without the RNA extraction step–Direct RT-LAMP, which could detect more than 1.43 x 103 copies within 15 min with a 100% probability in clinical evaluation test. Although the Direct RT-LAMP assay was less sensitive than the standard RT-LAMP, the Direct RT-LAMP assay can be available as the rapid first screening of COVID-19 in poorly equipped areas, such as rural areas in developing countries.

Validation of verbal autopsy and nasopharyngeal swab collection for the investigation of deaths at home during the COVID-19 pandemics in Brazil

PLoS Neglected Tropical Diseases News - 4 November 2020 - 10:00pm

by Pedro Mansueto Melo de Souza, Gunter Gerson, Josebson Silva Dias, Deborah Nunes de Melo, Sarlene Gomes de Souza, Erasmo Miessa Ruiz, Fabio Rocha Fernandes Tavora, Luciano Pamplona de Góes Cavalcanti

Informing children citizens efficiently to better engage them in the fight against COVID-19 pandemic

PLoS Neglected Tropical Diseases News - 4 November 2020 - 10:00pm

by Jean-Eric Ghia, Sophie Gaulin, Laure Ghia, Laure Garancher, Claude Flamand

Since the beginning of the year, the world’s attention has rightly been focused on the spread of the Coronavirus Disease 2019 (COVID-19) pandemic and the implementation of drastic mitigation strategies to limit disease transmission. However, public health information campaigns tailored to children are very rare. Now more than ever, at a time when some governments are taking populations out of lockdown and youth are returning to schools, children around the world need to fully grasp the modes of transmission of the disease, the health risks, the scientific notions of the immune system, the value of barrier measures, and the progress of scientific research. In the context of the COVID-19 pandemic, comics can be very useful for communicating quickly and effectively abstract and important information to children who might be under the influence of a large amount of sometimes contradictory information. Conveying precise, reliable, and accessible information to children is key in a world overwhelmingly impacted by the outbreak. This should be the role and the responsibility of world health official leaders and governments in compliance with the United Nations Convention on the Rights of the Child. In partnership with mainstream medias, consortia of scientists, communication experts, and education specialists, it is urgent that world leaders engage children in this worldwide public health fight.

A voluntary use of insecticide treated nets can stop the vector transmission of Chagas disease

PLoS Neglected Tropical Diseases News - 3 November 2020 - 10:00pm

by Cheol Yong Han, Habeeb Issa, Jan Rychtář, Dewey Taylor, Nancy Umana

One of the stated goals of the London Declaration on Neglected Tropical Diseases is the interruption of domiciliary transmissions of Chagas disease in the region of the Americas. We used a game-theoretic approach to assess the voluntary use of insecticide treated nets (ITNs) in the prevention of the spread of infection through vector bites. Our results show that individuals behave rationally and weigh the risks of insect bites against the cost of the ITNs. The optimal voluntary use of ITNs results in predicted incidence rates that closely track the real incidence rates in Latin America. This means that ITNs are effective and could be used to control the spread of the disease by relying on individual decisions rather than centralized policies. Our model shows that to completely eradicate the vector transmission through the voluntary individual use of ITNs, the cost of ITNs should be as low as possible.

Development of an antigen detection assay for early point-of-care diagnosis of <i>Zaire ebolavirus</i>

PLoS Neglected Tropical Diseases News - 3 November 2020 - 10:00pm

by Haley L. DeMers, Shihua He, Sujata G. Pandit, Emily E. Hannah, Zirui Zhang, Feihu Yan, Heather R. Green, Denise F. Reyes, Derrick Hau, Megan E. McLarty, Louis Altamura, Cheryl Taylor-Howell, Marcellene A. Gates-Hollingsworth, Xiangguo Qiu, David P. AuCoin

The 2013–2016 Ebola virus (EBOV) outbreak in West Africa and the ongoing cases in the Democratic Republic of the Congo have spurred development of a number of medical countermeasures, including rapid Ebola diagnostic tests. The likelihood of transmission increases as the disease progresses due to increasing viral load and potential for contact with others. Early diagnosis of EBOV is essential for halting spread of the disease. Polymerase chain reaction assays are the gold standard for diagnosing Ebola virus disease (EVD), however, they rely on infrastructure and trained personnel that are not available in most resource-limited settings. Rapid diagnostic tests that are capable of detecting virus with reliable sensitivity need to be made available for use in austere environments where laboratory testing is not feasible. The goal of this study was to produce candidate lateral flow immunoassay (LFI) prototypes specific to the EBOV glycoprotein and viral matrix protein, both targets known to be present during EVD. The LFI platform utilizes antibody-based technology to capture and detect targets and is well suited to the needs of EVD diagnosis as it can be performed at the point-of-care, requires no cold chain, provides results in less than twenty minutes and is low cost. Monoclonal antibodies were isolated, characterized and evaluated in the LFI platform. Top performing LFI prototypes were selected, further optimized and confirmed for sensitivity with cultured live EBOV and clinical samples from infected non-human primates. Comparison with a commercially available EBOV rapid diagnostic test that received emergency use approval demonstrates that the glycoprotein-specific LFI developed as a part of this study has improved sensitivity. The outcome of this work presents a diagnostic prototype with the potential to enable earlier diagnosis of EVD in clinical settings and provide healthcare workers with a vital tool for reducing the spread of disease during an outbreak.

Serious limitations of the current strategy to control Soil Transmitted Helminths and added value of ivermectin/Albendazole mass administration: A population-based observational study in Cameroon

PLoS Neglected Tropical Diseases News - 3 November 2020 - 10:00pm

by Linda Djune-Yemeli, Hugues C. Nana-Djeunga, Cédric G. Lenou-Nanga, Cyrille Donfo-Azafack, André Domche, Floribert Fossuo-Thotchum, Yannick Niamsi-Emalio, Francine Ntoumi, Joseph Kamgno

Background

Soil-transmitted helminth (STH) infections remain a public health concern in sub-Saharan Africa. School-based mass drug administration (MDA) using the anthelminthic drug Mebendazole/Albendazole have succeeded in controlling morbidity associated to these diseases but failed to interrupt their transmission. In areas were filarial diseases are co-endemic, another anthelminthic drug (Ivermectin) is distributed to almost the entire population, following the community-directed treatment with ivermectin (CDTI) strategy. Since ivermectin is a broad spectrum anthelmintic known to be effective against STH—we conducted cross-sectional surveys in two health districts with very contrasting histories of Ivermectin/Albendazole-based PC in order to investigate whether CDTI might have contributed in STH transmission interruption.

Methodology

Cross-sectional surveys were conducted in two health districts with similar socio-environmental patterns but with very contrasting CDTI histories (Akonolinga health district where CDTI was yet to be implemented vs. Yabassi health district where CDTI has been ongoing for two decades). Stool samples were collected from all volunteers aged >2 years old and analyzed using the Kato-Katz technique. Infections by different STH species were compared between Akonolinga and Yabassi health districts to decipher the impact of Ivermectin/Albendazole-based MDA on STH transmission.

Principal findings

A total of 610 and 584 participants aged 2–90 years old were enrolled in Akonolinga and Yabassi health districts, respectively. Two STH species (Ascaris lumbricoides and Trichuris trichiura) were found, with prevalence significantly higher in Akonolinga health district (43.3%; 95% CI: 38.1–46.6) compared to Yabassi health district and (2.5%; 95% CI: 1.1–5.1) (chi-square: 90.8; df: 1; p < 0.001).

Conclusion/significance

These findings (i) suggest that Mebendazole- or Albendazole-based MDA alone distributed only to at-risk populations might not be enough to eliminate STH, (ii) support the collateral impact of Ivermectin/Albendazole MDA on A. lumbricoides and T. trichiura infections, and (iii) suggest that Ivermectin/Albendazole-based PC could accelerate STH transmission interruption.

<i>Burkholderia pseudomallei</i> triggers canonical inflammasome activation in a human primary macrophage-based infection model

PLoS Neglected Tropical Diseases News - 2 November 2020 - 10:00pm

by Sabine Lichtenegger, Julia Stiehler, Sabine Saiger, Andrea Zauner, Barbara Kleinhappl, Claudia Bernecker, Peter Schlenke, Gabriel E. Wagner, Kathrin Krause, Magdalena Gastager, Ivo Steinmetz

Most of the current knowledge on Burkholderia pseudomallei-induced inflammasome activation and cell death in macrophages is derived from murine systems. Little is known about the involved bacterial structures and mechanisms in primary human macrophages. This is of particular relevance since murine and human macrophages as well as primary cells and cell lines differ in many aspects of inflammasome activation, including the proteins involved in the recognition of bacterial patterns. In this study, we therefore aimed (i) to establish an in vitro B. pseudomallei infection model with human monocyte-derived primary macrophages from single donors as these cells more closely resemble macrophages in the human host and (ii) to analyze B. pseudomallei-triggered cell death and bacterial elimination in those cells. Our results show that B. pseudomallei-infected primary human macrophages not only release the inflammasome-independent pro-inflammatory cytokines IL-8 and TNF-α, but are also engaged in canonical inflammasome activation as evidenced by caspase-1 and gasdermin D processing. Absence of the B. pseudomallei T3SS-3 needle protein BsaL, a potent activator of the canonical inflammasome, abolished lytic cell death, reduced IL-1β release, and caspase-1 and gasdermin D processing. IFN-γ, known to promote non-canonical inflammasome activation, did not influence pyroptosis induction or IL-1β release from infected primary human macrophages. Nevertheless, it reduced intracellular B. pseudomallei loads, an effect which was partially antagonist by the inhibition of NADPH oxidase. Overall, our data implicate T3SS-3 dependent inflammasome activation and IFN-γ induced immune mechanisms as critical defense mechanisms of human macrophages against B. pseudomallei. In addition, our infection model provides a versatile tool to study human host-pathogen interactions and has the potential to elucidate the role of human individual genetic variations in B. pseudomallei infections.

Baseline patterns of infection in regions of Benin, Malawi and India seeking to interrupt transmission of soil transmitted helminths (STH) in the DeWorm3 trial

PLoS Neglected Tropical Diseases News - 2 November 2020 - 10:00pm

by The DeWorm3 Trials Team

Global efforts to control morbidity associated with soil-transmitted helminth infections (STH) have focused largely on the targeted treatment of high-risk groups, including children and pregnant women. However, it is not clear when such programs can be discontinued and there are concerns about the sustainability of current STH control programs. The DeWorm3 project is a large multi-country community cluster randomized trial in Benin, India and Malawi designed to determine the feasibility of interrupting the transmission of STH using community-wide delivery of mass drug administration (MDA) with anthelmintics over multiple rounds. Here, we present baseline data and estimate key epidemiological parameters important in determining the likelihood of transmission interruption in the DeWorm3 trial. A baseline census was conducted in October-December 2017 in India, November-December 2017 in Malawi and in January-February 2018 in Benin. The baseline census enumerated all members of each household and collected demographic data and information on occupation, assets, and access to water, sanitation and hygiene (WASH). Each study site was divided into 40 clusters of at least 1,650 individuals per cluster. Clusters were randomized to receive twice yearly community-wide MDA with albendazole (GSK) targeting eligible individuals of all ages (20 clusters), or to receive the standard-of-care deworming program targeting children provided in each country. In each site, a randomly selected group of 150 individuals per cluster (6,000 total per site) was selected from the baseline census using stratified random sampling, and each individual provided a single stool sample for analysis of STH infection using the Kato-Katz technique. Study site, household and individual characteristics were summarized as appropriate. We estimated key epidemiological parameters including the force of infection and the degree of parasite aggregation within the population. The DeWorm3 sites range in population from 94,969 to 140,932. The population age distribution varied significantly by site, with the highest proportion of infants and young children in Malawi and the highest proportion of adults in India. The baseline age- and cluster-weighted prevalence, as measured by Kato-Katz, varied across sites and by species, Baseline hookworm prevalence in India was 21.4% (95% CI: 20.4–22.4%), while prevalence of Ascaris and Trichuris by Kato-Katz was low (0.1% and 0.3% overall). In Malawi, the overall age- and cluster-weighted STH prevalence was 7.7% (95% CI: 7.1–8.4%) predominantly driven by hookworm infections (7.4%) while Ascaris (0.1%) and Trichuris (0.3%) infections were rare. In Benin, the overall age- and cluster-weighted prevalence was significantly lower (5.6%, 95% CI: 5.1–6.2%) and Ascaris (2.0%, 95% CI: 1.6–2.3%) was more common than in other sites. Ascaris infections were more likely to be moderate- or heavy-intensity (43.7%, unweighted) compared to hookworm (5.0%). The force of infection for hookworm was highest in adults in India and Malawi but appeared relatively stable across age groups in Benin. These data demonstrate the significant variability between the sites in terms of demography, socio-economic status and environmental characteristics. In addition, the baseline prevalence and intensity data from DeWorm3 suggest that each site has unique epidemiologic characteristics that will be critical in determining correlates of achieving STH transmission interruption in the DeWorm3 trial. Trial registration: The trial was registered at ClinicalTrials.gov (NCT03014167).

Core components, concepts and strategies for parasitic and vector-borne disease elimination with a focus on schistosomiasis: A landscape analysis

PLoS Neglected Tropical Diseases News - 30 October 2020 - 9:00pm

by Nora Monnier, Tanja Barth-Jaeggi, Stefanie Knopp, Peter Steinmann

Efforts to control and eliminate human schistosomiasis have accelerated over the past decade. In a number of endemic countries and settings, interruption of schistosome transmission has been achieved. In others, Schistosoma infections continue to challenge program managers at different levels, from the complexity of the transmission cycle, over limited treatment options and lack of field-friendly accurate diagnostics, to controversy around adequate intervention strategies. We conducted a landscape analysis on parasitic and vector-borne disease elimination approaches with the aim to identify evidence-based strategies, core components and key concepts for achieving and sustaining schistosomiasis control and for progressing elimination efforts towards interruption of transmission in sub-Saharan Africa. A total of 118 relevant publications were identified from Web of Science, Pubmed and the grey literature and reviewed for their content. In addition, we conducted in-depth interviews with 23 epidemiologists, program managers, policymakers, donors and field researchers. Available evidence emphasizes the need for comprehensive, multipronged and long-term strategies consisting of multiple complementary interventions that must be sustained over time by political commitment and adequate funding in order to reach interruption of transmission. Based on the findings of this landscape analysis, we propose a comprehensive set of intervention strategies for schistosomiasis control and elimination. Before deployment, the proposed interventions will require review, evaluation and validation in the frame of an expert consultation as a step towards adaptation to specific contexts, conditions and settings. Field testing to ensure local relevance and effectiveness is paramount given the diversity of socio-ecological and epidemiological contexts.

Patients with skin smear positive leprosy in Bangladesh are the main risk factor for leprosy development: 21-year follow-up in the household contact study (COCOA)

PLoS Neglected Tropical Diseases News - 30 October 2020 - 9:00pm

by Emily E. V. Quilter, C. Ruth Butlin, Surendra Singh, Khorshed Alam, Diana N. J. Lockwood

Background

Leprosy transmission is ongoing; globally and within Bangladesh. Household contacts of leprosy cases are at increased risk of leprosy development. Identification of household contacts at highest risk would optimize this process.

Methods

The temporal pattern of new case presentation amongst household contacts was documented in the COCOA (Contact Cohort Analysis) study. The COCOA study actively examined household contacts of confirmed leprosy index cases identified in 1995, and 2000–2014, to provide evidence for timings of contact examination policies. Data was available on 9527 index cases and 38303 household contacts. 666 household contacts were diagnosed with leprosy throughout the follow-up (maximum follow-up of 21 years). Risk factors for leprosy development within the data analysed, were identified using Cox proportional hazard regression.

Findings

The dominant risk factor for household contacts developing leprosy was having a highly skin smear positive index case in the household. As the grading of initial slit skin smear of the index case increased from negative to high positive (4–6), the hazard of their associated household contacts developing leprosy increases by 3.14 times (p<0.001). Being a blood relative was not a risk factor, no gender differences in susceptibility were found.

Interpretation

We found a dominance of a single variable predicting risk for leprosy transmission–skin smear positive index cases. A small number of cases are maintaining transmission in the household setting. Focus should be performing contact examinations on these households and detecting new skin smear positive index cases. Conducting slit-skin smears on new cases is needed for predicting risk; such services need supporting. If skin smear positive cases are sustaining leprosy infection within the household setting, the administration of single-dose rifampicin (SDR) to household contacts as the sole intervention in Bangladesh will not be effective.

Correlation between thrombocytopenia and host response in severe fever with thrombocytopenia syndrome

PLoS Neglected Tropical Diseases News - 29 October 2020 - 9:00pm

by Xiao-Kun Li, Ke Dai, Zhen-Dong Yang, Chun Yuan, Ning Cui, Shao-Fei Zhang, Yuan-Yuan Hu, Zhi-Bo Wang, Dong Miao, Pan-He Zhang, Hao Li, Xiao-Ai Zhang, Yan-Qin Huang, Wei-Wei Chen, Jiu-Song Zhang, Qing-Bin Lu, Wei Liu

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV), with fatal outcome developed in approximately 17% of the cases. Thrombocytopenia is a hallmark feature of SFTS, and associated with a higher risk of fatal outcome, however, the pathophysiological involvement of platelet in the clinical outcome of SFTS remained under-investigated. In the current study, by retrospectively analyzing 1538 confirmed SFTS patients, we observed that thrombocytopenia was associated with enhanced activation of the cytokine network and the vascular endothelium, also with a disturbed coagulation response. The platelet phenotypes were also extensively altered in the process of thrombocytopenia development of SFTS patients. More importantly, all these disturbed host responses were related to the severity of thrombocytopenia, thus were considered to play in a synergistic way to influence the disease outcome. Moreover, the clinical effect of platelet transfusion was assessed by comparing two groups of patients with or without receiving this therapy. As a result, we observed no therapy effect in altering frequencies of fatal outcome, clinical bleeding development, or dynamic change of platelet count during the hospitalization. It’s suggested that platelet supplementation alone acted a minor role in improving disease outcome, therefore new therapeutic intervention to regulate host response should be proposed. The current results revealed some evidence of interrelationship between platelet count and clinical outcome of SFTS disease from the perspective of activation of the cytokine network, the vascular endothelium, and the coagulation/fibrinolysis system. These evaluations might help to attain a better understanding of the pathogenesis and therapy choice in SFTS.

A novel synthetic DNA vaccine elicits protective immune responses against Powassan virus

PLoS Neglected Tropical Diseases News - 29 October 2020 - 9:00pm

by Hyeree Choi, Sagar B. Kudchodkar, Michelle Ho, Emma L. Reuschel, Erin Reynolds, Ziyang Xu, Devivasha Bordoloi, Kenneth E. Ugen, Pablo Tebas, Joseph Kim, Mohamed Abdel-Mohsen, Saravanan Thangamani, David B. Weiner, Kar Muthumani

Powassan virus (POWV) infection is a tick-borne emerging infectious disease in the United States and North America. Like Zika virus, POWV is a member of the family Flaviviridae. POWV causes severe neurological sequalae, meningitis, encephalitis, and can cause death. Although the risk of human POWV infection is low, its incidence in the U.S. in the past 16 years has increased over 300%, urging immediate attention. Despite the disease severity and its growing potential for threatening larger populations, currently there are no licensed vaccines which provide protection against POWV. We developed a novel synthetic DNA vaccine termed POWV-SEV by focusing on the conserved portions of POWV pre-membrane and envelope (prMEnv) genes. A single immunization of POWV-SEV elicited broad T and B cell immunity in mice with minimal cross-reactivity against other flaviviruses. Antibody epitope mapping demonstrated a similarity between POWV-SEV-induced immune responses and those elicited naturally in POWV-infected patients. Finally, POWV-SEV induced immunity provided protection against POWV disease in lethal challenge experiments.

Capture-based enrichment of <i>Theileria parva</i> DNA enables full genome assembly of first buffalo-derived strain and reveals exceptional intra-specific genetic diversity

PLoS Neglected Tropical Diseases News - 29 October 2020 - 9:00pm

by Nicholas C. Palmateer, Kyle Tretina, Joshua Orvis, Olukemi O. Ifeonu, Jonathan Crabtree, Elliott Drabék, Roger Pelle, Elias Awino, Hanzel T. Gotia, James B. Munro, Luke Tallon, W. Ivan Morrison, Claudia A. Daubenberger, Vish Nene, Donald P. Knowles, Richard P. Bishop, Joana C. Silva

Theileria parva is an economically important, intracellular, tick-transmitted parasite of cattle. A live vaccine against the parasite is effective against challenge from cattle-transmissible T. parva but not against genotypes originating from the African Cape buffalo, a major wildlife reservoir, prompting the need to characterize genome-wide variation within and between cattle- and buffalo-associated T. parva populations. Here, we describe a capture-based target enrichment approach that enables, for the first time, de novo assembly of nearly complete T. parva genomes derived from infected host cell lines. This approach has exceptionally high specificity and sensitivity and is successful for both cattle- and buffalo-derived T. parva parasites. De novo genome assemblies generated for cattle genotypes differ from the reference by ~54K single nucleotide polymorphisms (SNPs) throughout the 8.31 Mb genome, an average of 6.5 SNPs/kb. We report the first buffalo-derived T. parva genome, which is ~20 kb larger than the genome from the reference, cattle-derived, Muguga strain, and contains 25 new potential genes. The average non-synonymous nucleotide diversity (πN) per gene, between buffalo-derived T. parva and the Muguga strain, was 1.3%. This remarkably high level of genetic divergence is supported by an average Wright’s fixation index (FST), genome-wide, of 0.44, reflecting a degree of genetic differentiation between cattle- and buffalo-derived T. parva parasites more commonly seen between, rather than within, species. These findings present clear implications for vaccine development, further demonstrated by the ability to assemble nearly all known antigens in the buffalo-derived strain, which will be critical in design of next generation vaccines. The DNA capture approach used provides a clear advantage in specificity over alternative T. parva DNA enrichment methods used previously, such as those that utilize schizont purification, is less labor intensive, and enables in-depth comparative genomics in this apicomplexan parasite.

“We have already heard that the treatment doesn't do anything, so why should we take it?”: A mixed method perspective on Chagas disease knowledge, attitudes, prevention, and treatment behaviour in the Bolivian Chaco

PLoS Neglected Tropical Diseases News - 29 October 2020 - 9:00pm

by Sandra Parisi, Miriam Navarro, Jeremy Douglas Du Plessis, Jonathan Phillip Shock, Boris Apodaca Michel, Minerva Lucuy Espinoza, Carolina Terán, Nino Antonio Calizaya Tapia, Katharina Oltmanns, Abundio Baptista Mora, Claudia Saveedra Irala, Angel Alberto Rivera Rojas, Gonzalo Rubilar, Thomas Zoller, Michael Pritsch

Background

Chagas disease (CD) is highly endemic in the Bolivian Chaco. The municipality of Monteagudo has been targeted by national interventions as well as by Médecins Sans Frontières to reduce infection rates, and to decentralize early diagnosis and treatment. This study seeks to determine the knowledge and attitudes of a population with increased awareness and to identify remaining factors and barriers for sustained vector control, health care seeking behaviour, and access, in order to improve future interventions.

Methodology/Principal findings

A cross-sectional survey was conducted among approximately 10% (n = 669) of the municipality of Monteagudo’s households that were randomly selected. Additionally, a total of 14 in-depth interviews and 2 focus group discussions were conducted with patients and key informants. Several attitudes and practices were identified that could undermine effective control against (re-)infection. Knowledge of clinical symptoms and secondary prevention was limited, and revealed specific misconceptions. Although 76% of the participants had been tested for CD, only 18% of those who tested positive concluded treatment with benznidazole (BNZ). Sustained positive serologies after treatment led to perceived ineffectiveness of BNZ. Moreover, access barriers such as direct as well as indirect costs, BNZ stock-outs and a fear of adverse reactions triggered by other community members made patients opt for alternative treatments against CD such as veterinary ivermectin, used by 28% of infected participants in our study. The lack of accessible care for chronic complications as well as socioeconomic consequences, such as the exclusion from both job opportunities and bank loans contributed to the ongoing burden of CD.

Conclusions/Significance

Large scale interventions should be accompanied by operational research in order to identify misconceptions and unintended consequences early on, to generate accessible data for future interventions, and for rigorous evaluation. An integrated, community-based approach tackling social determinants and including both traditional and animal health sectors might help to overcome current barriers and advocate for patients’ rights.

Impact of sars-cov-2 interventions on dengue transmission

PLoS Neglected Tropical Diseases News - 29 October 2020 - 9:00pm

by Jue Tao Lim, Borame Sue Lee Dickens, Lawrence Zheng Xiong Chew, Esther Li Wen Choo, Joel Ruihan Koo, Joel Aik, Lee Ching Ng, Alex R. Cook

An estimated 105 million dengue infections occur per year across 120 countries, where traditional vector control is the primary control strategy to reduce contact between mosquito vectors and people. The ongoing sars-cov-2 pandemic has resulted in dramatic reductions in human mobility due to social distancing measures; the effects on vector-borne illnesses are not known. Here we examine the pre and post differences of dengue case counts in Malaysia, Singapore and Thailand, and estimate the effects of social distancing as a treatment effect whilst adjusting for temporal confounders. We found that social distancing is expected to lead to 4.32 additional cases per 100,000 individuals in Thailand per month, which equates to 170 more cases per month in the Bangkok province (95% CI: 100–242) and 2008 cases in the country as a whole (95% CI: 1170–2846). Social distancing policy estimates for Thailand were also found to be robust to model misspecification, and variable addition and omission. Conversely, no significant impact on dengue transmission was found in Singapore or Malaysia. Across country disparities in social distancing policy effects on reported dengue cases are reasoned to be driven by differences in workplace-residence structure, with an increase in transmission risk of arboviruses from social distancing primarily through heightened exposure to vectors in elevated time spent at residences, demonstrating the need to understand the effects of location on dengue transmission risk under novel population mixing conditions such as those under social distancing policies.

The phosphoinositide regulatory network in <i>Trypanosoma brucei</i>: Implications for cell-wide regulation in eukaryotes

PLoS Neglected Tropical Diseases News - 29 October 2020 - 9:00pm

by Igor Cestari, Kenneth Stuart

The unicellular eukaryote Trypanosoma brucei undergoes extensive cellular and developmental changes during its life cycle. These include regulation of mammalian stage surface antigen variation and surface composition changes between life stages; switching between glycolysis and oxidative phosphorylation; differential mRNA editing; and changes in posttranscriptional gene expression, protein trafficking, organellar function, and cell morphology. These diverse events are coordinated and controlled throughout parasite development, maintained in homeostasis at each life stage, and are essential for parasite survival in both the host and insect vector. Described herein are the enzymes and metabolites of the phosphatidylinositol (PI) cellular regulatory network, its integration with other cellular regulatory systems that collectively control and coordinate these numerous cellular processes, including cell development and differentiation and the many associated complex processes in multiple subcellular compartments. We conclude that this regulation is the product of the organization of these enzymes within the cellular architecture, their activities, metabolite fluxes, and responses to environmental changes via signal transduction and other processes. We describe a paradigm for how these enzymes and metabolites could function to control and coordinate multiple cellular functions. The significance of the PI system’s regulatory functions in single-celled eukaryotes to metazoans and their potential as chemotherapeutic targets are indicated.

SARS-CoV-2 in the Amazon region: A harbinger of doom for Amerindians

PLoS Neglected Tropical Diseases News - 29 October 2020 - 9:00pm

by Juan David Ramírez, Emilia Mia Sordillo, Eduardo Gotuzzo, Carol Zavaleta, Daniel Caplivski, Juan Carlos Navarro, James Lee Crainey, Sergio Luiz Bessa Luz, Lourdes A. Delgado Noguera, Roxane Schaub, Cyril Rousseau, Giovanny Herrera, Maria A Oliveira-Miranda, Maria Teresa Quispe-Vargas, Peter J. Hotez, Alberto Paniz Mondolfi

As the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic continues to expand, healthcare resources globally have been spread thin. Now, the disease is rapidly spreading across South America, with deadly consequences in areas with already weakened public health systems. The Amazon region is particularly susceptible to the widespread devastation from Coronavirus disease 2019 (COVID-19) because of its immunologically fragile native Amerindian inhabitants and epidemiologic vulnerabilities. Herein, we discuss the current situation and potential impact of COVID-19 in the Amazon region and how further spread of the epidemic wave could prove devastating for many Amerindian people living in the Amazon rainforest.

<i>Schistosoma mansoni</i> infection as a trigger to collapsing glomerulopathy in a patient with high-risk <i>APOL1</i> genotype

PLoS Neglected Tropical Diseases News - 29 October 2020 - 9:00pm

by Precil D. Neves, Ramaiane A. Bridi, Janaína A. Ramalho, Lectícia B. Jorge, Elieser H. Watanabe, Andreia Watanabe, Luis Yu, Viktoria Woronik, Rafaela B. Pinheiro, Leonardo A. Testagrossa, Lívia B. Cavalcante, Denise M. Malheiros, Cristiane B. Dias, Luiz F. Onuchic

Background

Schistosoma mansoni schistosomiasis (SM) remains a public health problem in Brazil. Renal involvement is classically manifested as a glomerulopathy, most often membranoproliferative glomerulonephritis or focal and segmental glomerulosclerosis. We report a case of collapsing glomerulopathy (CG) associated with SM and high-risk APOL1 genotype (HRG).

Case report

A 35-year-old male was admitted for hypertension and an eight-month history of lower-limb edema, foamy urine, and increased abdominal girth. He had a recent diagnosis of hepatosplenic SM, treated with praziquantel, without clinical improvement. Laboratory tests revealed serum creatinine 1.89mg/dL, blood urea nitrogen (BUN) 24mg/dL, albumin 1.9g/dL, cholesterol 531mg/dL, low-density lipoprotein 426mg/dL, platelets 115000/mm3, normal C3/C4, antinuclear antibody (ANA), rheumatoid factor (RF), and antineutrophil cytoplasmic antibodies (ANCA), negative serologies for hepatitis C virus (HCV) and human immunodeficiency virus (HIV), HBsAg negative and AntiHBc IgG positive, no hematuria or leukocyturia, 24 hour proteinuria 6.56g and negative serum and urinary immunofixation. Kidney biopsy established the diagnosis of CG. A treatment with prednisone was started without therapeutic response, progressing to end-stage kidney disease 19 months later. Molecular genetics investigation revealed an HRG.

Conclusions

This is the first report of CG associated with SM in the setting of an HRG. This case highlights the two-hit model as a mechanism for CG pathogenesis, where the high-risk APOL1 genotype exerts a susceptibility role and SM infection serves as a trigger to CG.

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