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Helminth coinfection and COVID-19: An alternate hypothesis

PLoS Neglected Tropical Diseases News - 17 August 2020 - 9:00pm

by Russell Hays, Doris Pierce, Paul Giacomin, Alex Loukas, Peter Bourke, Robyn McDermott

How accurate is the diagnosis of rheumatic fever in Egypt? Data from the national rheumatic heart disease prevention and control program (2006-2018)

PLoS Neglected Tropical Diseases News - 17 August 2020 - 9:00pm

by Alaa Ghamrawy, Nermeen N. Ibrahim, Ekram W. Abd El-Wahab

Rheumatic heart disease (RHD) as a chronic sequela of repeated episodes of acute rheumatic fever (ARF), remains a cause of cardiac morbidity in Egypt although it is given full attention through a national RHD prevention and control program. The present report reviews our experience with subjects presenting with ARF or its sequelae in a single RHD centre and describes the disease pattern over the last decade. A cross-sectional study was conducted in El-Mahalla RHD centre between 2006 and 2018. A total of 17014 individual were enrolled and evaluated. Diagnosis ARF was based on the 2015 revised Jones criteria and RHD was ruled in by echocardiography. The majority of the screened subjects were female (63.2%), in the age group 5–15 years (64.6%), rural residents (61.2%), had primary education (43.0%), and of low socioeconomic standard (50.2%). The total percentage of cases presenting with ARF sequelae was 29.3% [carditis/RHD (10.8%), rheumatic arthritis (Rh.A) (14.9%), and Sydenham’s chorea (0.05%)]. Noticeably, 72% were free of any cardiac insult, of which 37.7% were victims of misdiagnoses made elsewhere by untrained practitioners who prescribed for them long term injectable long-acting penicillin [Benzathine Penicillin G (BPG)] without need. About 54% of the study cohort reported the occurrence of recurrent attacks of tonsillitis of which 65.2% underwent tonsillectomy. Among those who experienced tonsillectomy and/or received BPG in the past, 14.5% and 22.3% respectively had eventually developed RHD. Screening of family members of some RHD cases who needed cardiac surgery revealed 20.7% with undiagnosed ARF sequalae [RHD (56.0%) and Rh.A (52.2%)]. Upon the follow-up of RHD cases, 1.2% had improved, 98.4% were stable and 0.4% had their heart condition deteriorated. Misdiagnosis of ARF or its sequelae and poor compliance with BPG use may affect efforts being exerted to curtail the disease. Updating national guidelines, capacity building, and reliance on appropriate investigations should be emphasized. Since the genetic basis of RHD is literally confirmed, a family history of RHD warrants screening of all family members for early detection of the disease.

Comparison of World Health Organization and Demographic and Health Surveys data to estimate sub-national deworming coverage in pre-school aged children

PLoS Neglected Tropical Diseases News - 17 August 2020 - 9:00pm

by Nathan C. Lo, Ribhav Gupta, David G. Addiss, Eran Bendavid, Sam Heft-Neal, Alexei Mikhailov, Antonio Montresor, Pamela Sabina Mbabazi

Background

The key metric for monitoring the progress of deworming programs in controlling soil-transmitted helminthiasis (STH) is national drug coverage reported to the World Health Organization (WHO). There is increased interest in utilizing geographically-disaggregated data to estimate sub-national deworming coverage and equity, as well as gender parity. The Demographic and Health Surveys (DHS) offer a potential source of sub-national data. This study aimed to compare deworming coverage routinely reported to WHO and estimated by DHS in pre-school aged children to inform global STH measurement and evaluation.

Methodology

We compared sub-national deworming coverage in pre-school aged children reported to WHO and estimated by DHS aligned geospatially and temporally. We included data from Burundi (2016–2017), Myanmar (2015–2016), and the Philippines (2017) based on data availability. WHO provided data on the date and sub-national coverage per mass drug administration reported by Ministries of Health. DHS included maternally-reported deworming status within the past 6 months for each child surveyed. We estimated differences in sub-national deworming coverage using WHO and DHS data, and performed sensitivity analyses.

Principal findings

We compared data on pre-school aged children from 13 of 18 districts in Burundi (N = 6,835 in DHS), 11 of 15 districts in Myanmar (N = 1,462 in DHS) and 16 of 17 districts in the Philippines (N = 7,594 in DHS) following data exclusion. The national deworming coverages estimated by DHS in Burundi, Myanmar, and the Philippines were 75.5% (95% CI: 73.7%-77.7%), 47.0% (95% CI: 42.7%-51.3%), and 48.0% (95% CI: 46.0%-50.0%), respectively. The national deworming coverages reported by WHO in Burundi, Myanmar, and the Philippines were 80.1%, 93.6% and 75.7%, respectively. The mean absolute differences in district-level coverage reported to WHO and estimated by DHS in Burundi, Myanmar, and the Philippines were 9.5%, 41.5%, and 24.6%, respectively. Across countries, coverage reported to WHO was frequently higher than DHS estimates (32 of 40 districts). National deworming coverage from DHS estimates were similar by gender within countries.

Conclusions and significance

Agreement of deworming coverage reported to WHO and estimated by DHS data was heterogeneous across countries, varying from broadly compatible in Burundi to largely discrepant in Myanmar. DHS data could complement deworming data reported to WHO to improve data monitoring practices and serve as an independent sub-national source of coverage data.

Clinical, etiological and epidemiological investigations of hand, foot and mouth disease in southern Vietnam during 2015 – 2018

PLoS Neglected Tropical Diseases News - 17 August 2020 - 9:00pm

by Le Nguyen Thanh Nhan, Truong Huu Khanh, Nguyen Thi Thu Hong, Hoang Minh Tu Van, Le Nguyen Truc Nhu, Nguyen Thi Han Ny, Lam Anh Nguyet, Tran Tan Thanh, Nguyen To Anh, Vu Thi Ty Hang, Phan Tu Qui, Ho Lu Viet, Trinh Huu Tung, Do Quang Ha, Ha Manh Tuan, Guy Thwaites, Nguyen Van Vinh Chau, Louise Thwaites, Nguyen Thanh Hung, H. Rogier van Doorn, Le Van Tan

Hand, foot and mouth disease (HFMD) continues to challenge Asia with pandemic potential. In Vietnam, there have been two major outbreaks occurring during 2011–2012 (>200,000 hospitalizations and >200 deaths) and more recently in 2018 (>130,000 hospitalizations and 17 deaths). Given the high burden and the complex epidemic dynamics of HFMD, synthesizing its clinical and epidemiological data remains essential to inform the development of appropriate interventions and design public health measures. We report the results of a hospital-based study conducted during 2015–2018, covering the severe HFMD outbreak recently documented in Vietnam in 2018. The study was conducted at three major hospitals responsible for receiving HFMD patients from southern Vietnam with a population of over 40 million. A total of 19 enterovirus serotypes were detected in 1196 HFMD patients enrolled in the clinical study during 2015–2018, with enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), CV-A10 and CV-A16 being the major causes. Despite the emergence of coxsackieviruses, EV-A71 remains the leading cause of severe HFMD in Vietnam. EV-A71 was consistently detected at a higher frequency during the second half of the years. The emergence of EV-A71 subgenogroup C4 in late 2018 was preceded by its low activity during 2017–early 2018. Compared with EV-A71 subgenogroup B5, C4 was more likely to be associated with severe HFMD, representing the first report demonstrating the difference in clinical severity between subgenogroup C4 and B5, the two predominant EV-A71 subgenogroups causing HFMD worldwide. Our data have provided significant insights into important aspects of HFMD over four years (2015–2018) in Vietnam, and emphasize active surveillance for pathogen circulation remains essential to inform the local public health authorities in the development of appropriate intervention strategies to reduce the burden of this emerging infections. Multivalent vaccines are urgently needed to control HFMD.

Epidemiology of <i>Shigella</i> infections and diarrhea in the first two years of life using culture-independent diagnostics in 8 low-resource settings

PLoS Neglected Tropical Diseases News - 17 August 2020 - 9:00pm

by Elizabeth T. Rogawski McQuade, Fariha Shaheen, Furqan Kabir, Arjumand Rizvi, James A. Platts-Mills, Fatima Aziz, Adil Kalam, Shahida Qureshi, Sarah Elwood, Jie Liu, Aldo A. M. Lima, Gagandeep Kang, Pascal Bessong, Amidou Samie, Rashidul Haque, Estomih R. Mduma, Margaret N. Kosek, Sanjaya Shrestha, Jose Paulo Leite, Ladaporn Bodhidatta, Nicola Page, Ireen Kiwelu, Sadia Shakoor, Ali Turab, Sajid Bashir Soofi, Tahmeed Ahmed, Eric R. Houpt, Zulfiqar Bhutta, Najeeha Talat Iqbal

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (<10 years, RR: 1.14, 95% CI: 1.03, 1.26), initiating complementary foods before 3 months (RR: 1.10, 95% CI: 1.01, 1.20), and malnutrition (RR: 0.91, 95% CI: 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uniformly increased through the second year of life and was associated with intestinal inflammation. Culture missed most clinically relevant cases of severe diarrhea and dysentery.

Protection conferred by typhoid fever against recurrent typhoid fever in urban Kolkata

PLoS Neglected Tropical Diseases News - 17 August 2020 - 9:00pm

by Justin Im, Md. Taufiqul Islam, Deok Ryun Kim, Faisal Ahmmed, Yun Chon, K. Zaman, Ashraful Islam Khan, Mohammad Ali, Dipika Sur, Suman Kanungo, Shanta Dutta, Sujit K. Bhattacharya, Gordon Dougan, Kathryn E. Holt, Florian Marks, Jerome H. Kim, Firdausi Qadri, John D. Clemens

We evaluated the protection conferred by a first documented visit for clinical care of typhoid fever against recurrent typhoid fever prompting a visit. This study takes advantage of multi-year follow-up of a population with endemic typhoid participating in a cluster-randomized control trial of Vi capsular polysaccharide typhoid vaccine in Kolkata, India. A population of 70,566 individuals, of whom 37,673 were vaccinated with one dose of either Vi vaccine or a control (Hepatitis A) vaccine, were observed for four years. Surveillance detected 315 first typhoid visits, among whom 4 developed subsequent typhoid, 3 due to reinfection, defined using genomic criteria and corresponding to -124% (95% CI: -599, 28) protection by the initial illness. Point estimates of protection conferred by an initial illness were negative or negligible in both vaccinated and non-vaccinated subjects, though confidence intervals around the point estimates were wide. These data provide little support for a protective immunizing effect of clinically treated typhoid illness, though modest levels of protection cannot be excluded.

Fixed vs adjusted-dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 17 August 2020 - 9:00pm

by Agustín Ciapponi, Fabiana Barreira, Lucas Perelli, Ariel Bardach, Joaquim Gascón, Israel Molina, Carlos Morillo, Nilda Prado, Adelina Riarte, Faustino Torrico, Isabela Ribeiro, Juan Carlos Villar, Sergio Sosa-Estani

Chagas disease is a neglected disease that remains a public health threat, particularly in Latin America. The most important treatment options are nitroimidazole derivatives, such as nifurtimox and benznidazole (BZN). Some studies suggest that for adults seropositive to T. cruzi but without clinically evident chronic Chagas cardiomyopathy (CCC), a simple fixed-dose scheme of BZN could be equivalent to a weight-adjusted dose. We compared the efficacy and safety of a fixed dose of BZN with an adjusted dose for T. cruzi seropositive adults without CCC. We used the Cochrane methods, and reported according to the PRISMA statement. We included randomized controlled trials (RCTs) allocating participants to fixed and/or adjusted doses of BZN for T. cruzi seropositive adults without CCC. We searched (December 2019) Cochrane, MEDLINE, EMBASE, LILACS, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP), and contacted Chagas experts. Selection, data extraction, and risk of bias assessment, using the Cochrane tool, were performed independently by pairs of reviewers. Discrepancies were solved by consensus within the team. Primary outcomes were parasite‐related outcomes and efficacy or patient‐related safety outcomes. We conducted a meta-analysis using RevMan 5.3 software and used GRADE summary of finding tables to present the certainty of evidence by outcome. We identified 655 records through our search strategy and 10 studies (four of them ongoing) met our inclusion criteria. We did not find any study directly comparing fixed vs adjusted doses of BZN, however, some outcomes allowed subgroup comparisons between fixed and adjusted doses of BZN against placebo. Moderate-certainty evidence suggests no important subgroup differences for positive PCR at one year and for three safety outcomes (drug discontinuation, peripheral neuropathy, and mild rash). The same effect was observed for any serious adverse events (low-certainty evidence). All subgroups showed similar effects (I2 0% for all these subgroup comparisons but 32% for peripheral neuropathy), supporting the equivalence of BZN schemes. We conclude that there is no direct evidence comparing fixed and adjusted doses of BZN. Based on low to very low certainty of evidence for critical clinical outcomes and moderate certainty of evidence for important outcomes, fixed and adjusted doses may be equivalent in terms of safety and efficacy. An individual patient data network meta-analysis could better address this issue.

In-depth quantitative proteomics uncovers specie-specific metabolic programs in <i>Leishmania (Viannia)</i> species

PLoS Neglected Tropical Diseases News - 17 August 2020 - 9:00pm

by Nathalia Pinho, Jacek R. Wiśniewski, Geovane Dias-Lopes, Leonardo Saboia-Vahia, Ana Cristina Souza Bombaça, Camila Mesquita-Rodrigues, Rubem Menna-Barreto, Elisa Cupolillo, Jose Batista de Jesus, Gabriel Padrón, Patricia Cuervo

Leishmania species are responsible for a broad spectrum of diseases, denominated Leishmaniasis, affecting over 12 million people worldwide. During the last decade, there have been impressive efforts for sequencing the genome of most of the pathogenic Leishmania spp. as well as hundreds of strains, but large-scale proteomics analyses did not follow these achievements and the Leishmania proteome remained mostly uncharacterized. Here, we report a comprehensive comparative study of the proteomes of strains representing L. braziliensis, L. panamensis and L. guyanensis species. Proteins extracted by SDS-mediated lysis were processed following the multi-enzyme digestion-filter aided sample preparation (FASP) procedure and analysed by high accuracy mass spectrometry. “Total Protein Approach” and “Proteomic Ruler” were applied for absolute quantification of proteins. Principal component analysis demonstrated very high reproducibility among biological replicates and a very clear differentiation of the three species. Our dataset comprises near 7000 proteins, representing the most complete Leishmania proteome yet known, and provides a comprehensive quantitative picture of the proteomes of the three species in terms of protein concentration and copy numbers. Analysis of the abundance of proteins from the major energy metabolic processes allow us to highlight remarkably differences among the species and suggest that these parasites depend on distinct energy substrates to obtain ATP. Whereas L. braziliensis relies the more on glycolysis, L. panamensis and L. guyanensis seem to depend mainly on mitochondrial respiration. These results were confirmed by biochemical assays showing opposite profiles for glucose uptake and O2 consumption in these species. In addition, we provide quantitative data about different membrane proteins, transporters, and lipids, all of which contribute for significant species-specific differences and provide rich substrate for explore new molecules for diagnosing purposes. Data are available via ProteomeXchange with identifier PXD017696.

Generation of <i>Loa loa</i> infective larvae by experimental infection of the vector, <i>Chrysops silacea</i>

PLoS Neglected Tropical Diseases News - 17 August 2020 - 9:00pm

by Lontum B. Ndzeshang, Fanny F. Fombad, Abdel J. Njouendou, Valerine C. Chunda, Narcisse V.T. Gandjui, Desmond N. Akumtoh, Patrick W.N. Chounna, Andrew Steven, Nicolas P. Pionnier, Laura E. Layland, Manuel Ritter, Achim Hoerauf, Mark J. Taylor, Joseph D. Turner, Samuel Wanji

Basic and translational research on loiasis, a filarial nematode infection of medical importance, is impeded by a lack of suitable Loa loa infection models and techniques of obtaining and culturing life cycle stages. We describe the development of a new method for routine production of infective third-stage larvae (L3) of L. loa from the natural intermediate arthropod vector host, Chrysops silacea, following experimental infection with purified microfilariae. At 14-days post-infection of C. silacea, the fly survival rate was 43%. Survival was significantly higher in flies injected with 50 mf (55.2%) than those that received 100 mf (31.0%). However, yield per surviving fly and total yield of L3 was markedly higher in the group of flies inoculated with 100 mf (3474 vs 2462 L3 produced). The abdominal segment hosted the highest percentage recovery of L3 (47.7%) followed by head (34.5%) and thorax (17.9%). L. loa larval survival was higher than 90% after 30 days of in vitro culture. The in vitro moulting success rate to the L4 larval stage was 59.1%. After experimental infection of RAG2-/-IL-2γc-/—mice, the average L. loa juvenile adult worm recovery rate was 10.5% at 62 dpi. More than 87% of the worms were recovered from the muscles and subcutaneous tissues. Worms recovered measured an average 24.3 mm and 11.4 mm in length for females (n = 5) and males (n = 5), respectively. In conclusion, L. loa mf injected into C. silacea intrathoracically develop into infective larvae that remain viable and infective comparable to L3 obtained through natural feeding on the human host. This technique further advances the development of a full laboratory life cycle of L. loa where mf derived from experimentally-infected animals may be utilized to passage life cycle generations via intrathoracic injections of wild-caught vector hosts.

An Observational Study of Sepsis in Takeo Province Cambodia: An in-depth examination of pathogens causing severe infections

PLoS Neglected Tropical Diseases News - 17 August 2020 - 9:00pm

by Michelle Rozo, Kevin L. Schully, Casandra Philipson, Amitha Fitkariwala, Dararith Nhim, Tin Som, Darith Sieng, Bora Huot, Sokha Dul, Michael J. Gregory, Vireak Heang, Andrew Vaughn, Te Vantha, Angela M. Prouty, Chien-Chung Chao, Zhiwen Zhang, Tatyana Belinskaya, Logan J. Voegtly, Regina Z. Cer, Kimberly A. Bishop-Lilly, Chris Duplessis, James V. Lawler, Danielle V. Clark

The world’s most consequential pathogens occur in regions with the fewest diagnostic resources, leaving the true burden of these diseases largely under-represented. During a prospective observational study of sepsis in Takeo Province Cambodia, we enrolled 200 patients over an 18-month period. By coupling traditional diagnostic methods such as culture, serology, and PCR to Next Generation Sequencing (NGS) and advanced statistical analyses, we successfully identified a pathogenic cause in 46.5% of our cohort. In all, we detected 25 infectious agents in 93 patients, including severe threat pathogens such as Burkholderia pseudomallei and viral pathogens such as Dengue virus. Approximately half of our cohort remained undiagnosed; however, an independent panel of clinical adjudicators determined that 81% of those patients had infectious causes of their hospitalization, further underscoring the difficulty of diagnosing severe infections in resource-limited settings. We garnered greater insight as to the clinical features of severe infection in Cambodia through analysis of a robust set of clinical data.

Exploring factors affecting quality implementation of lymphatic filariasis mass drug administration in Bole and Central Gonja Districts in Northern Ghana

PLoS Neglected Tropical Diseases News - 17 August 2020 - 9:00pm

by Alfred Kwesi Manyeh, Latifat Ibisomi, Rohit Ramaswamy, Frank Baiden, Tobias Chirwa

Ghana has been implementing Mass Drug Administration (MDA) since the year 2001, and Lymphatic Filariasis transmission has been interrupted in 76 out of the 98 targeted districts. The remaining districts have a microfilaria prevalence above the 1% threshold needed for the interruption of transmission. This study assesses the level of lymphatic filariasis MDA coverage and explored factors affecting the quality of implementation of the MDA in the Bole and Central Gonja Districts of Northern Ghana. A concurrent mixed methods study design approach was used to provide both a quantitative and qualitative insight. A descriptive analysis was carried out, and the results are presented in tables and charts. The transcripts of the qualitative interviews were imported into Nvivo and framework methods of analysis were used. The results were summarized based on the themes and buttressed with narratives with key quotes presented within the texts. The overall MDA coverage in Central Gonja is 89.3% while that of Bole district is 82.9%. Refusal to ingest the drug and adverse drug reactions were higher in Bole district than the Central Gonja District. The persistent transmission of lymphatic filariasis in Bole District was characterized by poor community mobilization and sensitization, nonadherence to the directly observed treatment strategy, refusal to ingest the drug due to the fear of adverse drug reactions, inadequate knowledge and misconceptions about the disease. Reported mass drug administration coverage will not necessarily result into interruption of transmission of the disease without strict compliance to the directly observed treatment strategy, strong stakeholder engagement coupled with evidence-based context-specific multi-channel community education strategies with key educational messages on the cause of the disease and adverse drug reactions. While the clock for the elimination of lymphatic filariasis by the year 2020 and meeting of the Sustainable Development Goal 3 target 3.3 by 2030 is ticking, there is an urgent need for a concerted effort to improve the fidelity of the ongoing lymphatic filariasis MDA campaigns in the Bole District of Northern Ghana.

In target areas where human mosquito-borne diseases are diagnosed, the inclusion of the pre-adult mosquito aquatic niches parameters will improve the integrated mosquito control program

PLoS Neglected Tropical Diseases News - 14 August 2020 - 9:00pm

by Swapan Kumar Ghosh, Dipanjan Podder, Atanu Kumar Panja, Sabyasachi Mukherjee

In human communities inhabiting areas–such as West Bengal- India–where perpetuate the pre-imago & adult developmental stages of mosquitoes; many infectious diseases are still diagnosed such as Dengue, Malaria and Acute Encephalitis Syndrome. The control of the aquatic developmental stages is one of the easiest way to prevent the emergence of adults—the blood feeding adult females being thus prevented to sample their blood meal and to lay their eggs in the aquatic milieu where develop the aquatic pre-imaginal developmental stages. Moreover, reducing the adult population size also the probability of for the blood feeding adult female mosquitoes to act as hosts and vectors of the arboviruses such as dengue virus & Japanese encephalitis virus as well as of Plasmodium. Several environmental factors including water quality parameters are responsible for the selection of oviposition sites by the female mosquitoes. In our study, larval densities of three important mosquitoes (Aedes/A. albopictus, Anopheles/An. stephensi and Culex/C. vishnui) were measured and water qualities of their habitat i.e. pH, Specific Conductance, Dissolved Oxygen, Chemical Oxygen Demand, Total alkalinity (Talk), Hardness, Nitrate nitrogen and Ammonia nitrogen were analyzed in2017 and 2018 in many districts of West Bengal where humans beings are suffering from arboviruses and /or malaria. Whereas we have found positive correlation of density of C. vishnui and A. albopictus with the water factors except Chemical Oxygen Demand (COD) and Talk for An. stephensi all these factors except pH, COD and Talk have positive correlation. Hardness of the water shows positive correlation with the density of An. stephensi and C. vishnui but negative correlation with density of A. albopictus. Contour plot analysis demonstrates that occurrence of each mosquito species lies in between specific range of water factors. Inter- correlation analysis revealed that mosquitoes were negatively correlated with each other. A positive correlation of the water quality parameters and larval density, over two successive years, was also noticed. In conclusion, the increasing level of pollution due to industrial and other irresponsible waste management system which changes the water quality parameters may also influence mosquito population.

Diagnosis of neglected tropical diseases during and after the COVID-19 pandemic

PLoS Neglected Tropical Diseases News - 14 August 2020 - 9:00pm

by Dziedzom K. de Souza, Albert Picado, Sylvain Biéler, Sarah Nogaro, Joseph Mathu Ndung’u

The role of an active surveillance strategy of targeting household and neighborhood  contacts related to leprosy cases released from treatment in a low-endemic area of China

PLoS Neglected Tropical Diseases News - 14 August 2020 - 9:00pm

by Na Wang, Tongsheng Chu, Furong Li, Zhenzhen Wang, Dianchang Liu, Mingfei Chen, Honglei Wang, Guiye Niu, Dan Liu, Mingkai Zhang, Yuanyuan Xu, Yan Zhang, Jinghui Li, Zhen Li, Jiabao You, Liguo Mao, Huaizhang Li, Yongjin Chen, Hong Liu, Furen Zhang

Objective

Early diagnosis remains the primary goal for leprosy management programs. This study aims to determine whether active surveillance of patients with leprosy and their contact individuals increased identification of latent leprosy cases in the low-endemic areas.

Methods

This cross-sectional survey was carried out between October 2014 and August 2016 in 21 counties throughout Shandong Province. The survey was conducted among patients with leprosy released from treatment (RFT) and their contacts from both household and neighbors.

Results

A total of 2,210 RFT patients and 9,742 contacts comprising 7877 household contacts (HHCs), including 5,844 genetic related family members (GRFMs) and 2033 non-genetic related family members and 1,865 contacts living in neighboring houses (neighbor contacts, NCs), were recruited. Among identified individuals, one relapsed and 13 were newly diagnosed, giving a detection rate of 0.12%, corresponding to 120 times the passive case detection rate. Detection rates were similar for HHCs and NCs (0.114% vs. 0.214%, P = 0.287). Analysis of the family history of leprosy patients revealed clustering of newly diagnosed cases and association with residential coordinates of previously-diagnosed multibacillary leprosy cases.

Conclusion

Active case-finding programs are feasible and contributes to early case detection by tracking HHCs and NCs in low-endemic areas.

Simultaneous dengue and COVID-19 epidemics: Difficult days ahead?

PLoS Neglected Tropical Diseases News - 14 August 2020 - 9:00pm

by Mathieu Nacher, Maylis Douine, Mélanie Gaillet, Claude Flamand, Dominique Rousset, Cyril Rousseau, Chedli Mahdaoui, Stanley Carroll, Audrey Valdes, Nathalie Passard, Gabriel Carles, Félix Djossou, Magalie Demar, Loïc Epelboin

<i>Trypanosoma cruzi</i> loop-mediated isothermal amplification (<i>Trypanosoma cruzi</i> Loopamp) kit for detection of congenital, acute and Chagas disease reactivation

PLoS Neglected Tropical Diseases News - 14 August 2020 - 9:00pm

by Susana A. Besuschio, Albert Picado, Arturo Muñoz-Calderón, Diana P Wehrendt, Marisa Fernández, Alejandro Benatar, Zoraida Diaz-Bello, Cecilia Irurtia, Israel Cruz, Joseph M Ndung’u, María L Cafferata, Graciela Montenegro, Sergio Sosa Estani, Raúl H. Lucero, Belkisyole Alarcón de Noya, Silvia A Longhi, Alejandro G Schijman

A Trypanosoma cruzi Loopamp kit was recently developed as a ready-to-use diagnostic method requiring minimal laboratory facilities. We evaluated its diagnostic accuracy for detection of acute Chagas disease (CD) in different epidemiological and clinical scenarios. In this retrospective study, a convenience series of clinical samples (venous blood treated with EDTA or different stabilizer agents, heel-prick blood in filter paper or cerebrospinal fluid samples (CSF)) from 30 infants born to seropositive mothers (13 with congenital CD and 17 noninfected), four recipients of organs from CD donors, six orally–infected cases after consumption of contaminated guava juice and six CD patients coinfected with HIV at risk of CD reactivation (N = 46 patients, 46 blood samples and 1 CSF sample) were tested by T. cruzi Loopamp kit (Tc LAMP) and standardized quantitative real-time PCR (qPCR). T. cruzi Loopamp accuracy was estimated using the case definition in the different groups as a reference. Cohen’s kappa coefficient (κ) was applied to measure the agreement between Tc LAMP (index test) and qPCR (reference test). Sensitivity and specificity of T. cruzi Loopamp kit in blood samples from the pooled clinical groups was 93% (95% CI: 77–99) and 100% (95% CI: 80–100) respectively. The agreement between Tc LAMP and qPCR was almost perfect (κ = 0.92, 95% CI: 0.62–1.00). The T. cruzi Loopamp kit was sensitive and specific for detection of T. cruzi infection. It was carried out from DNA extracted from peripheral blood samples (via frozen EDTA blood, guanidine hydrochloride-EDTA blood, DNAgard blood and dried blood spots), as well as in CSF specimens infected with TcI or TcII/V/VI parasite populations. The T. cruzi Loopamp kit appears potentially useful for rapid detection of T. cruzi infection in congenital, acute and CD reactivation due to HIV infection.

<i>Leishmania naiffi</i> and <i>lainsoni</i> in French Guiana: Clinical features and phylogenetic variability

PLoS Neglected Tropical Diseases News - 14 August 2020 - 9:00pm

by Océane Ducharme, Stéphane Simon, Marine Ginouves, Ghislaine Prévot, Pierre Couppie, Magalie Demar, Romain Blaizot

In French Guiana, five species are associated with Cutaneous Leishmaniasis (CL). Though infections with Leishmania guyanensis, L. (V.) braziliensis and L. (L.) amazonensis have been extensively described, there are few available clinical and genetic data on L. (V.) lainsoni and L. (V.) naiffi. We determined the clinical and epidemiological features of all cases of CL due to L. (V.) naiffi and L. (V.) lainsoni diagnosed in French Guiana between 2003 and 2019. Phylogenetic analysis was performed by sequencing a portion of HSP70 and cyt b genes. Five cases of L. naiffi and 25 cases of L. lainsoni were reported. Patients infected by L. (V.) lainsoni were usually infected on gold camps, mostly along the Maroni river (60%), while L. naiffi was observed in French patients infected on the coast (100%). A high number of pediatric cases (n = 5; 20%) was observed for L. (V.) lainsoni. A mild clinical course was observed for all cases of L. (V.) naiffi. HSP70 and cyt b partial nucleotide sequence analysis revealed different geographical clusters within L. (V.) naiffi and L. (V.) lainsoni but no association were found between phylogenetic and clinical features. Our data suggest distinct socio-epidemiological features for these two Leishmania species. Patients seem to get infected with L. (V.) naiffi during leisure activities in anthropized coastal areas, while L. (V.) lainsoni shares common features with L. (V.) guyanensis and braziliensis and seems to be acquired during professional activities in primary forest regions. Phylogenetic analysis has provided information on the intraspecific genetic variability of L. (V.) naiffi and L. (V.) lainsoni and how these genotypes are distributed at the geographic level.

Crimean-Congo hemorrhagic fever virus strains Hoti and Afghanistan cause viremia and mild clinical disease in cynomolgus monkeys

PLoS Neglected Tropical Diseases News - 13 August 2020 - 9:00pm

by Robert W. Cross, Abhishek N. Prasad, Viktoriya Borisevich, Joan B. Geisbert, Krystle N. Agans, Daniel J. Deer, Karla A. Fenton, Thomas W. Geisbert

Background

Development of vaccines and therapies against Crimean-Congo hemorrhagic fever virus (CCHFV) have been hindered by the lack of immunocompetent animal models. Recently, a lethal nonhuman primate model based on the CCHFV Hoti strain was reported. CCHFV Hoti caused severe disease in cynomolgus monkeys with 75% lethality when given by the intravenous (i.v.) route.

Methodology/Principal findings

In a series of experiments, eleven cynomologus monkeys were exposed i.v. to CCHFV Hoti and four macaques were exposed i.v. to CCHFV Afghanistan. Despite transient viremia and changes in clinical pathology such as leukopenia and thrombocytopenia developing in all 15 animals, all macaques survived to the study endpoint without developing severe disease.

Conclusions/Significance

We were unable to attribute differences in the results of our study versus the previous report to differences in the CCHFV Hoti stock, challenge dose, origin, or age of the macaques. The observed differences are most likely the result of the outbred nature of macaques and low animal numbers often used by necessity and for ethical considerations in BSL-4 studies. Nonetheless, while we were unable to achieve severe disease or lethality, the CCHFV Hoti and Afghanistan macaque models are useful for screening medical countermeasures using biomarkers including viremia and clinical pathology to assess efficacy.

Xenodiagnosis to address key questions in visceral leishmaniasis control and elimination

PLoS Neglected Tropical Diseases News - 13 August 2020 - 9:00pm

by Om Prakash Singh, Epco Hasker, Marleen Boelaert, David Sacks, Shyam Sundar

Visceral leishmaniasis (VL) remains an important public health issue worldwide causing substantial morbidity and mortality. The Indian subcontinent accounted for up to 90% of the global VL burden in the past but made significant progress during recent years and is now moving towards elimination. However, to achieve and sustain elimination of VL, knowledge gaps on infection reservoirs and transmission need to be addressed urgently. Xenodiagnosis is the most direct way for testing the infectiousness of hosts to the vectors and can be used to investigate the dynamics and epidemiology of Leishmania donovani transmission. There are, however, several logistic and ethical issues with xenodiagnosis that need to be addressed before its application on human subjects. In the current Review, we discuss the critical knowledge gaps in VL transmission and the role of xenodiagnosis in disease transmission dynamics along with its technical challenges. Establishment of state of the art xenodiagnosis facilities is essential for the generation of much needed evidence in the VL elimination initiative.

Ecological processes underlying the emergence of novel enzootic cycles: Arboviruses in the neotropics as a case study

PLoS Neglected Tropical Diseases News - 13 August 2020 - 9:00pm

by Sarah Guth, Kathryn A. Hanley, Benjamin M. Althouse, Mike Boots

Pathogens originating from wildlife (zoonoses) pose a significant public health burden, comprising the majority of emerging infectious diseases. Efforts to control and prevent zoonotic disease have traditionally focused on animal-to-human transmission, or “spillover.” However, in the modern era, increasing international mobility and commerce facilitate the spread of infected humans, nonhuman animals (hereafter animals), and their products worldwide, thereby increasing the risk that zoonoses will be introduced to new geographic areas. Imported zoonoses can potentially “spill back” to infect local wildlife—a danger magnified by urbanization and other anthropogenic pressures that increase contacts between human and wildlife populations. In this way, humans can function as vectors, dispersing zoonoses from their ancestral enzootic systems to establish reservoirs elsewhere in novel animal host populations. Once established, these enzootic cycles are largely unassailable by standard control measures and have the potential to feed human epidemics. Understanding when and why translocated zoonoses establish novel enzootic cycles requires disentangling ecologically complex and stochastic interactions between the zoonosis, the human population, and the natural ecosystem. In this Review, we address this challenge by delineating potential ecological mechanisms affecting each stage of enzootic establishment—wildlife exposure, enzootic infection, and persistence—applying existing ecological concepts from epidemiology, invasion biology, and population ecology. We ground our discussion in the neotropics, where four arthropod-borne viruses (arboviruses) of zoonotic origin—yellow fever, dengue, chikungunya, and Zika viruses—have separately been introduced into the human population. This paper is a step towards developing a framework for predicting and preventing novel enzootic cycles in the face of zoonotic translocations.

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