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Six rounds of annual praziquantel treatment during a national helminth control program significantly reduced schistosome infection and morbidity levels in a cohort of schoolchildren in Zimbabwe

PLoS Neglected Tropical Diseases News - 22 June 2020 - 9:00pm

by Takafira Mduluza, Caitlin Jones, Derick N. M. Osakunor, Rivka Lim, Julius K. Kuebel, Isaac Phiri, Portia Manangazira, Paradzayi Tagwireyi, Francisca Mutapi

Background

The World Health Organization recommends that schistosomiasis be treated through Mass Drug Administration (MDA). In line with this recommendation, Zimbabwe commenced a national helminth control program in 2012 targeting schoolchildren throughout the country for 6 years. This study, part of a larger investigation of the impact of helminth treatment on overall health of the children, determined the effect of annual praziquantel treatment on schistosome infection and morbidity in a cohort of children during Zimbabwe’s 6-year national helminth control program.

Methodology/Principal findings

A school-based longitudinal study was carried out in 35 sentinel sites across Zimbabwe from September 2012 to November 2017. The sentinel sites were selected following a countrywide survey conducted in 280 primary schools. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni was diagnosed using both the Kato Katz and formol ether concentration techniques. S. haematobium morbidity was determined through detection of macro and microhaematuria. A cohort of children aged 6–15 years old were surveyed annually before MDA and 6 weeks post treatment. Maximum treatment coverage reached 90% over the 6 rounds of MDA. At baseline S. haematobium infection prevalence and intensity were 31.7% (95% CI = 31.1–32.2) and 28.75 eggs/10ml urine (SEM = 0.81) respectively, while S. mansoni prevalence and intensity were 4.6% (95% CI = 4.4–4.8) and 0.28 eggs/25mg (SEM = 0.02). Prior to the 6th round of MDA, S. haematobium infection prevalence had reduced to 1.56% (p<0.001) and infection intensity was to 0.07 (SEM 0.02). Six weeks later after the 6th MDA, both were 0. Similarly the prevalence of S. haematobium morbidity as indicted by haematuria also fell significantly from 32.3% (95% CI = 29.9–34.6) to 0% (p< 0.0001) prior to the final MDA. For S.mansoni, both prevalence and intensity had decreased to 0 prior to the 6th MDA. After 6 rounds of annual MDA, prevalence and intensity of both schistosome species decreased significantly to 0% (p< 0.0001).

Conclusion

Zimbabwe’s helminth control program significantly reduced schistosome infection intensity and prevalence and urogenital schistosomiasis morbidity prevalence in a cohort of school-aged children, moving the schistosome prevalence in the children from moderate to low by WHO classification. These findings will inform the design of the country next stage interventions for helminth control and eventual elimination.

Source attribution of human echinococcosis: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 22 June 2020 - 9:00pm

by Paul R. Torgerson, Lucy J. Robertson, Heidi L. Enemarkx, Junwei Foehr, Joke W. B. van der Giessen, Christian M. O. Kapel, Ivana Klun, Chiara Trevisan

Background

A substantial proportion of echinococcosis transmission to humans via contamination of food has been assumed. However, the relative importance of food as a transmission vehicle has previously been estimated through expert opinion rather than empirical data.

Objective

To find and evaluate empirical data that could be used to estimate the source attribution of echinococcosis, in particular the proportion that is transmitted through contaminated food.

Methods

A systematic review was undertaken to identify reports on the risk factors for human cystic (CE) and alveolar (AE) echinococcosis. Data bases searched included PubMed, Scopus, Web of Knowledge, Cab Direct, Science Direct, Google Scholar, eLIBRARY.RU, CyberLeninka, CNKI and VIP. Search terms included Echinococc*, hydatid, epidemiology, logistic regression, risk factors, odds ratio, relative risk, risk factors. Reports, including grey literature where available, that had suitable data were selected and data were extracted. The main pathways of transmission were hypothesised to be contact with the definitive host, contaminated water, contaminated food and contaminated environment (other than food). For each study the attributable fraction for these potential sources of infection was calculated from the data presented. A meta-analysis was then undertaken to obtain pooled estimates for the relative contribution of these transmission pathways.

Results

Data from 28 cross-sectional studies and 14 case-control studies were extracted. There was strong evidence for transmission by direct contact with dogs for both CE and AE. The estimated attributable fractions were 26.1% (CI 13.8%-39.6%) and 34.4% (CI 20.7% -48.2%) respectively. Transmission through contaminated water was estimated to be responsible for approximately 29.4% (CI 12.1%-51.7%) for CE and 24.8% (CI 10.6% to 42.6%) for AE. Contaminated food may be responsible for approximately 23.4% of CE cases (CI 2.1%-47.3%). Globally, there was insufficient evidence to conclude AE can be transmitted by food, although case control studies from low human incidence areas suggested that possibly 32.5% (CI 10.0%-53.2%) could be transmitted by food. There was also insufficient evidence that direct contact with foxes was a significant source of human disease. There were no suitable studies with a risk of environmental contact reported, but the residual attributable fraction thatwould likely include this pathway was approximately 30.4% for CE and 11.1% for AE.

Conclusions

The results support the hypothesis that dog contact and drinking contaminated water are major pathways of transmission of both CE and AE. For contaminated food, the results are less consistent, but suggest that it is an important transmission pathway and provide better evidence than expert elicitations as previously used.

Tracing temporal and geographic distribution of resistance to pyrethroids in the arboviral vector <i>Aedes albopictus</i>

PLoS Neglected Tropical Diseases News - 22 June 2020 - 9:00pm

by Alessandra Tancredi, Davide Papandrea, Michele Marconcini, Rebeca Carballar-Lejarazu, Mauricio Casas-Martinez, Eugenia Lo, Xiao-Guang Chen, Anna R. Malacrida, Mariangela Bonizzoni

Background

The arboviral vector Aedes albopictus became established on all continents except Antarctica in the past 50 years. A consequence of its rapid global invasion is the transmission of diseases previously confined to the tropics and subtropics occurring in temperate regions of the world, including the re-emergence of chikungunya and dengue in Europe. Application of pyrethroids is among the most widely-used interventions for vector control, especially in the presence of an arboviral outbreak. Studies are emerging that reveal phenotypic resistance and monitor mutations at the target site, the para sodium channel gene, primarily on a local scale.

Methods

A total of 512 Ae. albopictus mosquitoes from twelve geographic sites, including those from the native home range and invaded areas, were sampled between 2011 and 2018, and were analyzed at five codons of the para sodium channel gene with mutations predictive of resistance phenotype. Additionally, to test for the origin of unique kdr mutations in Mexico, we analyzed the genetic connectivity of southern Mexico mosquitoes with mosquitoes from home range, the Reunion Island, America and Europe.

Results

We detected mutations at all tested positions of the para sodium channel gene, with heterozygotes predominating and rare instance of double mutants. We observed an increase in the distribution and frequency of F1534C/L/S mutations in the ancestral China population and populations in the Mediterranean Greece, the appearance of the V1016G/I mutations as early as 2011 in Italy and mutations at position 410 and 989 in Mexico. The analyses of the distribution pattern of kdr alleles and haplotype network analyses showed evidence for multiple origins of all kdr mutations.

Conclusions

Here we provide the most-up-to-date survey on the geographic and temporal distribution of pyrethroid-predictive mutations in Ae. albopictus by combining kdr genotyping on current and historical samples with published data. While we confirm low levels of pyrethroid resistance in most analyzed samples, we find increasing frequencies of F1534C/S and V1016G in China and Greece or Italy, respectively. The observed patterns of kdr allele distribution support the hypothesis that on site emergence of resistance has contributed more than spread of resistance through mosquito migration/invasions to the current widespread of kdr alleles, emphasizing the importance of local surveillance programs and resistance management.

Unusual dominant genotype NIA1 of <i>Enterocytozoon bieneusi</i> in children in Southern Xinjiang, China

PLoS Neglected Tropical Diseases News - 22 June 2020 - 9:00pm

by Meng Qi, Fuchang Yu, Aiyun Zhao, Ying Zhang, Zilin Wei, Dongfang Li, Longxian Zhang

Enterocytozoon bieneusi is the mainly pathologies or intestinal disorders that causes approximately 90% of reported cases of human microsporidiosis. To understand the prevalence and genotype distribution of E. bieneusi in the Xinjiang Uygur Autonomous Region, China, 609 fecal samples were collected from children in kindergarten in Southern Xinjiang and screened for this pathogen by PCR and sequencing of the internal transcribed spacer (ITS). Thirty-six fecal samples (5.9%, 36/609) were positive for E. bieneusi, with the highest prevalence observed in children from Yopurga (17.5%, 11/63). Nine genotypes were identified, of which six were known (A, CHN6, D, EbpA, KB-1, and NIA1) and three were novel (CXJH1, CXJH2 and CXJH3). Genotype NIA1 was most prevalent (52.8%, 19/36), followed by genotypes D (16.7%, 6/36), A (8.3%, 3/36), and EbpA (8.3%, 3/36). The remaining five genotypes were detected in one sample each. Phylogenetic analysis revealed that the E. bieneusi isolates clustered into two groups, one consisting of six genotypes (Group 1: A, CXJH1, D, EbpA, KB-1, and NIA1) and another consisting of three genotypes (Group 2: CHN6, CXJH2, and CXJH3). Our results confirmed that infection of E. bieneusi unusual dominant genotype NIA1 occurs in children in Xinjiang, China. Further epidemiological studies must be conducted to clarify potential sources of E. bieneusi infection in this area.

Efficacy and safety of single 40 mg/kg oral praziquantel in the treatment of schistosomiasis in preschool-age versus school-age children: An individual participant data meta-analysis

PLoS Neglected Tropical Diseases News - 22 June 2020 - 9:00pm

by Piero L. Olliaro, Jean T. Coulibaly, Amadou Garba, Christine Halleux, Jennifer Keiser, Charles H. King, Francisca Mutapi, Eliézer K. N’Goran, Giovanna Raso, Alexandra U. Scherrer, José Carlos Sousa-Figueiredo, Katarina Stete, Jürg Utzinger, Michel T. Vaillant

Background

Better knowledge of the efficacy and safety of single 40 mg/kg oral praziquantel in preschool-age children is required, should preventive chemotherapy programs for schistosomiasis be expanded to include this age group.

Methodology

We analyzed individual participant-level data from 16 studies (13 single-arm or cohort studies and three randomized trials), amounting to 683 preschool-age children (aged <6 years) and 2,010 school-age children (aged 6–14 years). Children had a documented Schistosoma mansoni or S. haematobium infection, were treated with single 40 mg/kg oral praziquantel, and assessed between 21 and 60 days post-treatment. Efficacy was expressed as arithmetic mean and individual egg reduction rate (ERR) and meta-analyzed using general linear models and mixed models. Safety was summarized using reported adverse events (AEs).

Principal findings

Preschool-age children had significantly lower baseline Schistosoma egg counts and more losses to follow-up compared to school-age children. No difference in efficacy was found between preschool- and school-age children using a general linear model of individual-participant ERR with baseline log-transformed egg count as covariate and study, age, and sex as fixed variables, and a mixed model with a random effect on the study. Safety was reported in only four studies (n = 1,128 individuals); few AEs were reported in preschool-age children 4 and 24 hours post-treatment as well as at follow-up. Three severe but not serious AEs were recorded in school-age children during follow-up.

Conclusions/Significance

There is no indication that single 40 mg/kg oral praziquantel would be less efficacious and safe in preschool-age children compared to school-age children, with the caveat that only few randomized comparisons exist between the two age groups. Preventive chemotherapy might therefore be extended to preschool-age children, with proper monitoring of its efficacy and safety.

Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey

PLoS Neglected Tropical Diseases News - 22 June 2020 - 9:00pm

by Andrew D. Haddow, Unai Perez-Sautu, Michael R. Wiley, Lynn J. Miller, Adrienne E. Kimmel, Lucia M. Principe, Suzanne E. Wollen-Roberts, Joshua D. Shamblin, Stephanie M. Valdez, Lisa H. Cazares, William D. Pratt, Franco D. Rossi, Luis Lugo-Roman, Sina Bavari, Gustavo F. Palacios, Aysegul Nalca, Farooq Nasar, M. Louise M. Pitt

Mosquito-borne and sexual transmission of Zika virus (ZIKV), a TORCH pathogen, recently initiated a series of large epidemics throughout the Tropics. Animal models are necessary to determine transmission risk and study pathogenesis, as well screen antivirals and vaccine candidates. In this study, we modeled mosquito and sexual transmission of ZIKV in the African green monkey (AGM). Following subcutaneous, intravaginal or intrarectal inoculation of AGMs with ZIKV, we determined the transmission potential and infection dynamics of the virus. AGMs inoculated by all three transmission routes exhibited viremia and viral shedding followed by strong virus neutralizing antibody responses, in the absence of clinical illness. All four of the subcutaneously inoculated AGMs became infected (mean peak viremia: 2.9 log10 PFU/mL, mean duration: 4.3 days) and vRNA was detected in their oral swabs, with infectious virus being detected in a subset of these specimens. Although all four of the intravaginally inoculated AGMs developed virus neutralizing antibody responses, only three had detectable viremia (mean peak viremia: 4.0 log10 PFU/mL, mean duration: 3.0 days). These three AGMs also had vRNA and infectious virus detected in both oral and vaginal swabs. Two of the four intrarectally inoculated AGMs became infected (mean peak viremia: 3.8 log10 PFU/mL, mean duration: 3.5 days). vRNA was detected in oral swabs collected from both of these infected AGMs, and infectious virus was detected in an oral swab from one of these AGMs. Notably, vRNA and infectious virus were detected in vaginal swabs collected from the infected female AGM (peak viral load: 7.5 log10 copies/mL, peak titer: 3.8 log10 PFU/mL, range of detection: 5–21 days post infection). Abnormal clinical chemistry and hematology results were detected and acute lymphadenopathy was observed in some AGMs. Infection dynamics in all three AGM ZIKV models are similar to those reported in the majority of human ZIKV infections. Our results indicate that the AGM can be used as a surrogate to model mosquito or sexual ZIKV transmission and infection. Furthermore, our results suggest that AGMs are likely involved in the enzootic maintenance and amplification cycle of ZIKV.

Histological and quantitative polymerase chain reaction-based analysis of Buruli ulcer using mapping biopsy method

PLoS Neglected Tropical Diseases News - 22 June 2020 - 9:00pm

by Toshifumi Takahashi, Miho Kabuto, Gen Nakanishi, Toshihiro Tanaka, Noriki Fujimoto

Background

In Japan, Buruli ulcer cases are often advanced, requiring surgical treatment. However, extensive debridement is often difficult because of cosmetic and functional sequelae. Moreover, the lesions are complicated and composed of edematous erythema, necrotic ulcer, and erythematous skin lesions caused by a paradoxical reaction, which also make it difficult to perform adequate debridement.

Methodology/Principal findings

We performed quantitative polymerase chain reaction (PCR) analysis for IS2404 using 29 samples taken from mapping biopsy. We evaluated the relationship among mycobacterial burden, histopathological findings, and clinical outcomes using 83 tissue samples taken from mapping biopsy and debrided Buruli ulcer. On quantitative PCR, the Cp values of IS2404 amplification were substantially different in each site. The major histological findings could be divided into massive subcutaneous necrosis with scant inflammatory cell infiltration and dense inflammatory cell infiltration. Of the 84 sites, 34 were subjected to repeated histological evaluations. In these sites, histological necrosis did not disappear over time despite standard antibiotic treatment. In contrast, the ulcers were cured and no recurrences were observed without resecting the 11 biopsied sites that lacked histological necrosis. Although quantitative PCR revealed that a lower Cp value of IS2404 was associated with histological massive necrosis, sites that showed lower Cp values clinically did not always need debridement.

Conclusion/Significance

Our descriptive study revealed that the histological findings and amounts of mycobacterial DNA differed according to the sites despite being found in one lesion. Our results showed that the need for surgical debridement in each site was correlated with histological necrosis without inflammatory cell infiltration, as the inflammation is supposed to represent an active host immune response rather than mycobacterial burden. We suggest that the debridement of lesions with histological necrosis in mapping biopsy may be useful for Japanese cases with unsuccessful standard antibiotic treatment to achieve sufficient clinical improvement.

Coordination among neighbors improves the efficacy of Zika control despite economic costs

PLoS Neglected Tropical Diseases News - 22 June 2020 - 9:00pm

by Natalie J. Lemanski, Samantha R. Schwab, Dina M. Fonseca, Nina H. Fefferman

Emerging mosquito-borne viruses like Zika, dengue, and chikungunya pose a major threat to public health, especially in low-income regions of Central and South America, southeast Asia, and the Caribbean. Outbreaks of these diseases are likely to have long-term social and economic consequences due to Zika-induced congenital microcephaly and other complications. Larval control of the container-inhabiting mosquitoes that transmit these infections is an important tool for mitigating outbreaks. However, metapopulation theory suggests that spatiotemporally uneven larvicide treatment can impede control effectiveness, as recolonization compensates for mortality within patches. Coordinating the timing of treatment among patches could therefore substantially improve epidemic control, but we must also consider economic constraints, since coordination may have costs that divert resources from treatment. To inform practical disease management strategies, we ask how coordination among neighbors in the timing of mosquito control efforts influences the size of a mosquito-borne infectious disease outbreak under the realistic assumption that coordination has costs. Using an SIR (Susceptible-Infectious-Recovered)/metapopulation model of mosquito and disease dynamics, we examine whether sharing surveillance information and coordinating larvicide treatment among neighboring patches reduces human infections when incorporating coordination costs. We examine how different types of coordination costs and different surveillance methods jointly influence the effectiveness of larval control. We find that the effect of coordination depends on both costs and the type of surveillance used to inform treatment. With epidemiological surveillance, coordination improves disease outcomes, even when costly. With demographic surveillance, coordination either improves or hampers disease control, depending on the type of costs and surveillance sensitivity. Our results suggest coordination among neighbors can improve management of mosquito-borne epidemics under many, but not all, assumptions about costs. Therefore, estimating coordination costs is an important step for most effectively applying metapopulation theory to strategies for managing outbreaks of mosquito-borne viral infections.

Evidence of transovarial transmission of Chikungunya and Dengue viruses in field-caught mosquitoes in Kenya

PLoS Neglected Tropical Diseases News - 19 June 2020 - 9:00pm

by Claire J. Heath, Elysse N. Grossi-Soyster, Bryson A. Ndenga, Francis M. Mutuku, Malaya K. Sahoo, Harun N. Ngugi, Joel O. Nbakaya, Peter Siema, Uriel Kitron, Nayer Zahiri, Jimmy Hortion, Jesse J. Waggoner, Charles H. King, Benjamin A. Pinsky, A. Desiree LaBeaud

Arboviruses are among the most important emerging pathogens due to their increasing public health impact. In Kenya, continued population growth and associated urbanization are conducive to vector spread in both urban and rural environments, yet mechanisms of viral amplification in vector populations is often overlooked when assessing risks for outbreaks. Thus, the characterization of local arbovirus circulation in mosquito populations is imperative to better inform risk assessments and vector control practices. Aedes species mosquitoes were captured at varying stages of their life cycle during different seasons between January 2014 and May 2016 at four distinct sites in Kenya, and tested for chikungunya (CHIKV), dengue (DENV) and Zika (ZIKV) viruses by RT-PCR. CHIKV was detected in 45 (5.9%) and DENV in 3 (0.4%) mosquito pools. No ZIKV was detected. Significant regional variation in prevalence was observed, with greater frequency of CHIKV on the coast. DENV was detected exclusively on the coast. Both viruses were detected in immature mosquitoes of both sexes, providing evidence of transovarial transmission of these arboviruses in local mosquitoes. This phenomenon may be driving underlying viral maintenance that may largely contribute to periodic re-emergence among humans in Kenya.

Cross-species reactivity of antibodies against <i>Plasmodium vivax</i> blood-stage antigens to <i>Plasmodium knowlesi</i>

PLoS Neglected Tropical Diseases News - 19 June 2020 - 9:00pm

by Fauzi Muh, Namhyeok Kim, Myat Htut Nyunt, Egy Rahman Firdaus, Jin-Hee Han, Mohammad Rafiul Hoque, Seong-Kyun Lee, Ji-Hoon Park, Robert W. Moon, Yee Ling Lau, Osamu Kaneko, Eun-Taek Han

Malaria is caused by multiple different species of protozoan parasites, and interventions in the pre-elimination phase can lead to drastic changes in the proportion of each species causing malaria. In endemic areas, cross-reactivity may play an important role in the protection and blocking transmission. Thus, successful control of one species could lead to an increase in other parasite species. A few studies have reported cross-reactivity producing cross-immunity, but the extent of cross-reactive, particularly between closely related species, is poorly understood. P. vivax and P. knowlesi are particularly closely related species causing malaria infections in SE Asia, and whilst P. vivax cases are in decline, zoonotic P. knowlesi infections are rising in some areas. In this study, the cross-species reactivity and growth inhibition activity of P. vivax blood-stage antigen-specific antibodies against P. knowlesi parasites were investigated. Bioinformatics analysis, immunofluorescence assay, western blotting, protein microarray, and growth inhibition assay were performed to investigate the cross-reactivity. P. vivax blood-stage antigen-specific antibodies recognized the molecules located on the surface or released from apical organelles of P. knowlesi merozoites. Recombinant P. vivax and P. knowlesi proteins were also recognized by P. knowlesi- and P. vivax-infected patient antibodies, respectively. Immunoglobulin G against P. vivax antigens from both immune animals and human malaria patients inhibited the erythrocyte invasion by P. knowlesi. This study demonstrates that there is extensive cross-reactivity between antibodies against P. vivax to P. knowlesi in the blood stage, and these antibodies can potently inhibit in vitro invasion, highlighting the potential cross-protective immunity in endemic areas.

Evaluation of a rapid diagnostic test for <i>Schistosoma mansoni</i> infection based on the detection of circulating cathodic antigen in urine in Central Sudan

PLoS Neglected Tropical Diseases News - 19 June 2020 - 9:00pm

by Mohamed M. Elbasheir, Ibrahim A. Karti, Elwaleed M. Elamin

Background

The Kato-Katz thick smear is the standard test for the diagnosis of Schistosoma mansoni infection, but the sensitivity of this technique is low. As an alternative, (CCA) strip test has been evaluated with the conclusion that it may replace the Kato-Katz method in areas where prevalences are moderate or high. Therefore, this study was undertaken to evaluate the performance of the CCA strip test in the diagnosis and monitoring of S. mansoni infection in Sudan.

Methodology

489 stool and urine samples were collected from school children in endemic area of Sudan to determine the validity of CCA strip test based on duplicate Kato-Katz thick smear technique. Additional, 118 samples from known non schistosome-endemic area were collected to assess the CCA cross reactivity with other pathogens rather than schistosomiasis. The stability of CCA in urine samples was determined by consecutive examination of 40 positive CCA urine samples. 81 samples were used to evaluate the CCA strip test for the assessment of cure one week, three weeks and six weeks post Praziquantel treatment.

Principal findings

Assuming parasitological test results as the gold standard, the sensitivity, specificity, positive predictive and negative predictive values of the CCA test were 96%, 85.4%, 78.5% and 97.5% respectively. There was no cross reactivity with other pathogens. The CCA strip test showed high accuracy in monitoring of treatment 93.8% and 100% after three and six weeks of administration of Praziquantel respectively. The stability of the CCA for long time in the urine revealed a safety transportation and shipment of the samples whenever it demanded.

Conclusion/Significance

The uses of urine CCA strip test in the field would provide more accurate information on the epidemiology and monitoring of the Schistosoma mansoni infection in endemic areas of schistosomiasis than the conventional parasitological method. Moreover, The stability of CCA in urine samples confirms a safety transportation period of the samples whenever it required.

Conversion of asymptomatic infection to symptomatic visceral leishmaniasis: A study of possible immunological markers

PLoS Neglected Tropical Diseases News - 18 June 2020 - 9:00pm

by Vidya Nand Rabi Das, Sanjiva Bimal, Niyamat Ali Siddiqui, Ashish Kumar, Krishna Pandey, Sanjay Kumar Sinha, Roshan Kamal Topno, Vijay Mahentesh, Ashish Kumar Singh, Chandra Shekhar Lal, Subhankar Kumar Singh, Pradeep Das

Introduction

Presence of asymptomatic individualsin endemic areas is common. The possible biomarkers inasymptomatic individualspatients once they get exposed to infection as well as following conversion to symptomatic disease are yet to be identified.We identified asymptomatic Visceral leishmaniasis (VL) infection amongst rK39+sorted direct agglutination test positive (DAT+) endemic healthy population and confirmed it by quantitative PCR(qPCR).The immunological determinants such as Adenosine deaminase (ADA), Interferon gamma (IFN-γ), Tumour Necrosis Factor alpha (TNF-α) and Interleukin 10 (IL-10)were examined to predict probable biomarkers for conversion to symptomatic VL.

Methods

Sample size was 5794 healthy individuals from VL endemic region. Antibody tests(DAT &rK39) were performed and later a qPCR assay was employed using kDNA specific primers and probes. Immunological biomarkers examined were ADA level by ADA–MTP kit and quantitative cytokines(IFN-γ, IL-10 and TNF-α) by ELISA.

Results

120 asymptomatic individuals of 308 rK39sero-positives were DAT positive comprising of 56 with previous history and 64 with no history of VL. RT-PCR confirmed asymptomatic VL in 42 sero-positives. These were followed up through repeated qPCR and evaluation of immunological determinants. We observed10 symptomatic cases converted from a total of 42 asymptomatic individualssubjects identified at base-line. The level of ADA, IL-10 and IFN-γ remained consistently high in asymptomatic individuals and amongst these, ADA and IL-10 but not IFN-γ remained higher at the development of clinical symptoms into active VL suspects. On the contrary, there was no significant change in the mean concentration of TNF-α at both stages of the disease.

Discussion

We surmise from our data that considerable proportion of asymptomatic cases can be a reservoir and play a crucial role in transmission of visceral leishmaniasis in endemic areas.The data also suggests that ADA and IL-10 can serve as a potential biomarker during the conversion of asymptomatic into symptomatic VL.

Intermittent pain of the pelvis in a Syrian woman

PLoS Neglected Tropical Diseases News - 18 June 2020 - 9:00pm

by Benjamin T. Schleenvoigt, Bernhard Theis, Michaela Wüst, Christina Forstner, Mathias W. Pletz, Stefan Hagel

Adaptive iron utilization compensates for the lack of an inducible uptake system in <i>Naegleria fowleri</i> and represents a potential target for therapeutic intervention

PLoS Neglected Tropical Diseases News - 18 June 2020 - 9:00pm

by Dominik Arbon, Kateřina Ženíšková, Jan Mach, Maria Grechnikova, Ronald Malych, Pavel Talacko, Robert Sutak

Naegleria fowleri is a single-cell organism living in warm freshwater that can become a deadly human pathogen known as a brain-eating amoeba. The condition caused by N. fowleri, primary amoebic meningoencephalitis, is usually a fatal infection of the brain with rapid and severe onset. Iron is a common element on earth and a crucial cofactor for all living organisms. However, its bioavailable form can be scarce in certain niches, where it becomes a factor that limits growth. To obtain iron, many pathogens use different machineries to exploit an iron-withholding strategy that has evolved in mammals and is important to host-parasite interactions. The present study demonstrates the importance of iron in the biology of N. fowleri and explores the plausibility of exploiting iron as a potential target for therapeutic intervention. We used different biochemical and analytical methods to explore the effect of decreased iron availability on the cellular processes of the amoeba. We show that, under iron starvation, nonessential, iron-dependent, mostly cytosolic pathways in N. fowleri are downregulated, while the metal is utilized in the mitochondria to maintain vital respiratory processes. Surprisingly, N. fowleri fails to respond to acute shortages of iron by inducing the reductive iron uptake system that seems to be the main iron-obtaining strategy of the parasite. Our findings suggest that iron restriction may be used to slow the progression of infection, which may make the difference between life and death for patients.

Correction: Evaluation of nitazoxanide treatment following triclabendazole failure in an outbreak of human fascioliasis in Upper Egypt

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

by Haidi Karam-Allah Ramadan, Waleed Attia Hassan, Nahed Ahmed Elossily, Alzahraa Abdelraouf Ahmad, Adnan Ahmed Mohamed, Alaa Soliman Abd- Elkader, Eman M. Nagiub Abdelsalam, Hani M. J. Khojah

Incidence of snakebites in Can Tho Municipality, Mekong Delta, South Vietnam—Evaluation of the responsible snake species and treatment of snakebite envenoming

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

by Vo Van Thang, Truong Quy Quoc Bao, Hoang Dinh Tuyen, Ralf Krumkamp, Le Hoang Hai, Nguyen Hai Dang, Cao Minh Chu, Joerg Blessmann

Background

Data on incidence of snakebites and the responsible snake species are largely missing in Vietnam and comprehensive national guidelines for management of snakebite envenoming are not yet available. They are needed to estimate the scope of this health problem, to assess the demand for snake antivenom and to ensure the best possible treatment for snakebite victims.

Methodology/Principle findings

A cross-sectional community-based survey was conducted from January to April 2018. Multistage cluster sampling was applied and snakebite incidence in Can Tho municipality, excluding two central districts of Can Tho city, was calculated at 48 (95%-confidence interval (CI): 20.5–99.8) snakebites per 100,000 person-years. Seven snakebite victims found during the survey reported 3 bites from green pit vipers and 4 bites from non-venomous snakes. In 2017 two treatment centres for snakebite envenoming in Can Tho city, the Military Hospital 121 and the Paediatric Hospital, received 520 admissions of snakebite victims. Two hundred sixty-seven came from Can Tho Municipality and 253 from neighbouring provinces. According to these data, the incidence of snakebites for Can Tho municipality was calculated at 21 (95%-CI: 18.5–23.7) snakebites per 100,000 person-years. Incidence was 14 (95%-CI: 12–17) snakebites per 100,000 person years in those 7 districts of the municipality which were part of the community survey. Green pit vipers were responsible for 92% of snakebite envenoming. Antivenom, antibiotics and corticosteroids were administered to 405 (90%), 379 (84%), and 310 (69%) out of 450 patients, respectively.

Conclusions

Incidence of snakebites in Can Tho Municipality is relatively low and green pit vipers are responsible for the vast majority of bites. Approximately one third of snakebite patients sought medical care in hospitals and although hospital data still underestimate the real incidence of snakebites, these statistics are valuable and can be obtained fast and inexpensively. Evaluation of patients’ records indicates the need for development of guidelines for management of snakebite envenoming in Vietnam to ensure a rational use of antivenom and ancillary treatments.

Social marketing interventions for the prevention and control of neglected tropical diseases: A systematic review

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

by Nathaly Aya Pastrana, Maria Lazo-Porras, J. Jaime Miranda, David Beran, L. Suzanne Suggs

Background

Social marketing is an approach to behavior change that contributes to disease prevention and control. This study aimed to understand how social marketing interventions have addressed neglected tropical diseases (NTDs). It examined the characteristics, breadth of coverage, and outcomes of social marketing interventions focused on the prevention and control of these diseases.

Methodology/Principal findings

Studies published in any language between January 1971 and April 2017, targeting at least one of the 17 NTDs prioritized in the World Health Organization (WHO) NTD Roadmap were considered. Included studies had interventions that applied both, at least one core social marketing concept, “social behavioral influence”, and one social marketing technique, “integrated intervention mix”, described in the Hierarchical Model of Social Marketing. This review is registered with PROSPERO CRD42017063858. Twenty interventions, addressing eight NTDs, met the inclusion criteria. They focused on behaviors related to four of the five WHO public health strategies for NTDs. Most interventions incorporated the concepts “relationship building” and “public / people orientation focus”, and the technique “insight-driven segmentation”. All the interventions reported changing behavioral determinants such as knowledge, 19 reported behavior change, and four influenced health outcomes.

Conclusion/Significance

Evidence from this study shows that social marketing has been successfully used to address behaviors related to most of the five public health strategic interventions for NTDs recommended by the WHO. It is suggested that social marketing interventions for the prevention and control of NTDs be grounded on an understanding of the audience and adapted to the contexts intervened. Building stakeholder relationships as early as possible, and involving the publics could help in reaching NTD outcomes. Elements of the intervention mix should be integrated and mutually supportive. Incorporating health education and capacity building, as well as being culturally appropriate, is also relevant. It is recommended that ongoing discussions to formulate the targets and milestones of the new global Roadmap for NTDs integrate social marketing as an approach to overcome these diseases.

First international external quality assessment scheme of nucleic acid amplification tests for the detection of <i>Schistosoma</i> and soil-transmitted helminths, including <i>Strongyloides</i>: A pilot study

PLoS Neglected Tropical Diseases News - 16 June 2020 - 9:00pm

by Piet Cools, Lisette van Lieshout, Rob Koelewijn, David Addiss, Sitara S. R. Ajjampur, Mio Ayana, Richard S. Bradbury, Jason L. Cantera, Daniel Dana, Kerstin Fischer, Rubina Imtiaz, Joyce Kabagenyi, James Lok, James McCarthy, Rojelio Mejia, Zeleke Mekonnen, Sammy M. Njenga, Nurulhasanah Othman, Hongguang Shao, Rebecca Traub, Marjan Van Esbroeck, Jozef Vercruysse, Johnny Vlaminck, Steven A. Williams, Jaco J. Verweij, Jaap J. van Hellemond, Bruno Levecke

Background

Nucleic acid amplification tests (NAATs) are increasingly being used as diagnostic tools for soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Ancylostoma duodenale and A. ceylanicum), Strongyloides stercoralis and Schistosoma in human stool. Currently, there is a large diversity of NAATs being applied, but an external quality assessment scheme (EQAS) for these diagnostics is lacking. An EQAS involves a blinded process where test results reported by a laboratory are compared to those reported by reference or expert laboratories, allowing for an objective assessment of the diagnostic performance of a laboratory. In the current study, we piloted an international EQAS for these helminths (i) to investigate the feasibility of designing and delivering an EQAS; (ii) to assess the diagnostic performance of laboratories; and (iii) to gain insights into the different NAAT protocols used.

Methods and principal findings

A panel of twelve stool samples and eight DNA samples was validated by six expert laboratories for the presence of six helminths (Ascaris, Trichuris, N. americanus, Ancylostoma, Strongyloides and Schistosoma). Subsequently this panel was sent to 15 globally dispersed laboratories. We found a high degree of diversity among the different DNA extraction and NAAT protocols. Although most laboratories performed well, we could clearly identify the laboratories that were poorly performing.

Conclusions/Significance

We showed the technical feasibility of an international EQAS for the NAAT of STHs, Strongyloides and Schistosoma. In addition, we documented that there are clear benefits for participating laboratories, as they can confirm and/or improve the diagnostic performance of their NAATs. Further research should aim to identify factors that explain poor performance of NAATs.

Multivariate time-series analysis of biomarkers from a dengue cohort offers new approaches for diagnosis and prognosis

PLoS Neglected Tropical Diseases News - 16 June 2020 - 9:00pm

by Baptiste Vasey, Anuraj H. Shankar, Bobby Brooke Herrera, Aniuska Becerra, Kris Xhaja, Marion Echenagucia, Sara R. Machado, Diana Caicedo, John Miller, Paolo Amedeo, Elena N. Naumova, Irene Bosch, Norma Blumenfeld deBosch

Dengue is a major public health problem worldwide with distinct clinical manifestations: an acute presentation (dengue fever, DF) similar to other febrile illnesses (OFI) and a more severe, life-threatening form (severe dengue, SD). Due to nonspecific clinical presentation during the early phase of dengue infection, differentiating DF from OFI has remained a challenge, and current methods to determine severity of dengue remain poor early predictors. We present a prospective clinical cohort study conducted in Caracas, Venezuela from 2001–2005, designed to determine whether clinical and hematological parameters could distinguish DF from OFI, and identify early prognostic biomarkers of SD. From 204 enrolled suspected dengue patients, there were 111 confirmed dengue cases. Piecewise mixed effects regression and nonparametric statistics were used to analyze longitudinal records. Decreased serum albumin and fibrinogen along with increased D-dimer, thrombin-antithrombin complex, activated partial thromboplastin time and thrombin time were prognostic of SD on the day of defervescence. In the febrile phase, the day-to-day rates of change in serum albumin and fibrinogen concentration, along with platelet counts, were significantly decreased in dengue patients compared to OFI, while the day-to-day rates of change of lymphocytes (%) and thrombin time were increased. In dengue patients, the absolute lymphocytes to neutrophils ratio showed specific temporal increase, enabling classification of dengue patients entering the critical phase with an area under the ROC curve of 0.79. Secondary dengue patients had elongation of Thrombin time compared to primary cases while the D-dimer formation (fibrinolysis marker) remained always lower for secondary compared to primary cases. Based on partial analysis of 31 viral complete genomes, a high frequency of C-to-T transitions located at the third codon position was observed, suggesting deamination events with five major hot spots of amino acid polymorphic sites outside in non-structural proteins. No association of severe outcome was statistically significant for any of the five major polymorphic sites found. This study offers an improved understanding of dengue hemostasis and a novel way of approaching dengue diagnosis and disease prognosis using piecewise mixed effect regression modeling. It also suggests that a better discrimination of the day of disease can improve the diagnostic and prognostic classification power of clinical variables using ROC curve analysis. The piecewise mixed effect regression model corroborated key early clinical determinants of disease, and offers a time-series approach for future vaccine and pathogenesis clinical studies.

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