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A family-based intervention for prevention and self-management of disabilities due to leprosy, podoconiosis and lymphatic filariasis in Ethiopia: A proof of concept study

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Anna T. van‘t Noordende, Moges Wubie Aycheh, Tesfaye Tadesse, Tanny Hagens, Eva Haverkort, Alice P. Schippers

A key issue for persons with leprosy-, lymphatic filariasis- and podoconiosis-related disabilities is the life-long need to practice self-management routines. This is difficult to sustain without regular encouragement and support of others. Family-based support may be a sustainable and feasible strategy to practice self-management routines. This proof of concept study aimed to develop and pilot a family-based intervention to support prevention and self-management of leprosy, lymphatic filariasis and podoconiosis-related disabilities in Ethiopia. We used a quasi-experimental pre/post intervention study design with a mixed methods approach. The study population included persons affected by leprosy, lymphatic filariasis and podoconiosis and their family members. All persons affected had visible impairments due to their condition. We collected physical impairment outcomes, data on activity limitations, stigma and family quality of life using the SALSA scale (range 0–80), the SARI stigma scale (range 0–63) and the Beach Centre Family Quality of Life scale (range 0–125) and conducted in-depth interviews and focus group discussions. Quantitative data were analysed using paired t-tests, unequal variances t-tests, linear regression and binary logistic regression. Qualitative data were coded using open, inductive coding and content analysis. The family-based intervention consisted of self-management of disabilities, awareness raising and socio-economic empowerment. The intervention was delivered over several monthly group meetings over the course of several months. A total of 275 (100%) persons affected attended at least one session with a family member, and 215 (78%) attended at least three sessions. There was no significant improvement in eye and hand problems after the intervention. However, foot and leg impairments, number of acute attacks, lymphedema and shoe wearing all significantly improved at follow-up. In addition, family quality of life significantly improved from 67.4 at baseline to 89.9 at follow-up for family members and from 76.9 to 84.1 for persons affected (p<0.001). Stigma levels significantly decreased from 24.0 at baseline to 16.7 at follow-up (p<0.001). Activity levels improved, but not significantly. This proof of concept study showed that the family-based intervention had a positive effect on impairments and self-management of disabilities, family quality of life and stigma. We recommend a large-scale efficacy trial, using a randomised controlled trial and validated measurement tools, to determine its effectiveness and long-term sustainability.

Biogeographical venom variation in the Indian spectacled cobra (<i>Naja naja</i>) underscores the pressing need for pan-India efficacious snakebite therapy

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by R. R. Senji Laxme, Saurabh Attarde, Suyog Khochare, Vivek Suranse, Gerard Martin, Nicholas R. Casewell, Romulus Whitaker, Kartik Sunagar

Background

Snake venom composition is dictated by various ecological and environmental factors, and can exhibit dramatic variation across geographically disparate populations of the same species. This molecular diversity can undermine the efficacy of snakebite treatments, as antivenoms produced against venom from one population may fail to neutralise others. India is the world’s snakebite hotspot, with 58,000 fatalities and 140,000 morbidities occurring annually. Spectacled cobra (Naja naja) and Russell’s viper (Daboia russelii) are known to cause the majority of these envenomations, in part due to their near country-wide distributions. However, the impact of differing ecologies and environment on their venom compositions has not been comprehensively studied.

Methods

Here, we used a multi-disciplinary approach consisting of venom proteomics, biochemical and pharmacological analyses, and in vivo research to comparatively analyse N. naja venoms across a broad region (>6000 km; seven populations) covering India’s six distinct biogeographical zones.

Findings

By generating the most comprehensive pan-Indian proteomic and toxicity profiles to date, we unveil considerable differences in the composition, pharmacological effects and potencies of geographically-distinct venoms from this species and, through the use of immunological assays and preclinical experiments, demonstrate alarming repercussions on antivenom therapy. We find that commercially-available antivenom fails to effectively neutralise envenomations by the pan-Indian populations of N. naja, including a complete lack of neutralisation against the desert Naja population.

Conclusion

Our findings highlight the significant influence of ecology and environment on snake venom composition and potency, and stress the pressing need to innovate pan-India effective antivenoms to safeguard the lives, limbs and livelihoods of the country’s 200,000 annual snakebite victims.

Surveillance of <i>Trypanosoma cruzi</i> infection in Triatomine vectors, feral dogs and cats, and wild animals in and around El Paso county, Texas, and New Mexico

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Felipe Rodriguez, Brenda S. Luna, Olivia Calderon, Claudia Manriquez-Roman, Karsten Amezcua-Winter, Jonathan Cedillo, Rebeca Garcia-Vazquez, Itzel A. Tejeda, Alvaro Romero, Kenneth Waldrup, Douglas M. Watts, Camilo Khatchikian, Rosa A. Maldonado

The causative agent of Chagas disease, Trypanosoma cruzi, is transmitted by triatomine vectors. The insect is endemic in the Americas, including the United States, where epidemiological studies are limited, particularly in the Southwestern region. Here, we have determined the prevalence of T. cruzi in triatomines, and feral cats and dogs, and wild animals, the infecting parasite genotypes and the mammalian host bloodmeal sources of the triatomines at four different geographical sites in the U.S.-Mexico border, including El Paso County, Texas, and nearby cities in New Mexico. Using qualitative polymerase chain reaction to detect T. cruzi infections, we found 66.4% (n = 225) of triatomines, 45.3% (n = 95) of feral dogs, 39.2% (n = 24) of feral cats, and 71.4% (n = 7) of wild animals positive for T. cruzi. Over 95% of T. cruzi genotypes or discrete typing units (DTUs) identified were TcI and some TcIV. Furthermore, Triatoma rubida was the triatomine species most frequently (98.2%) collected in all samples analyzed. These findings suggest a high prevalence of T. cruzi infections among triatomines, and feral and wild animals in the studied sites. Therefore, our results underscore the urgent need for implementation of a systematic epidemiological surveillance program for T. cruzi infections in insect vectors, and feral and wild animals, and Chagas disease in the human population in the southwestern region of the United States.

Malaria and helminth co-infections in children living in endemic countries: A systematic review with meta-analysis

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Muhammed O. Afolabi, Boni M. Ale, Edgard D. Dabira, Schadrac C. Agbla, Amaya L. Bustinduy, Jean Louis A. Ndiaye, Brian Greenwood

Background

Current knowledge on the burden of, and interactions between malaria and helminth co-infections, as well as the impact of the dual infections on anaemia, remains inconclusive. We have conducted a systematic review with meta-analysis to update current knowledge as a first step towards developing and deploying coordinated approaches to the control and, ultimately, elimination of malaria-helminth co-infections among children living in endemic countries.

Methodology/Principal findings

We searched Medline, Embase, Global Health and Web of Science from each database inception until 16 March 2020, for peer-reviewed articles reporting malaria-helminth co-infections in children living in a LMIC. No language restriction was applied. Following removal of duplicates, two reviewers independently screened the studies for eligibility. We used the summary odds ratio (OR) and 95% confidence intervals (CI) as a measure of association (random-effects model). We also performed Chi-square heterogeneity test based on Cochrane’s Q and evaluated the severity of heterogeneity using I2 statistics. The included studies were examined for publication bias using a funnel plot and statistical significance was assessed using Egger’s test (bias if p<0.1).Fifty-five of the 3,507 citations screened were eligible, 28 of which had sufficient data for meta-analysis. The 28 studies enrolled 22, 114 children in 13 countries across sub-Saharan Africa, Southeast Asia and South America. Overall, the pooled estimates showed a prevalence of Plasmodium-helminth co-infections of 17.7% (95% CI 12.7–23.2%). Summary estimates from 14 studies showed a lower odds of P. falciparum infection in children co-infected with Schistosoma spp (OR: 0.65; 95%CI: 0.37–1.16). Similar lower odds of P. falciparum infection were observed from the summary estimates of 24 studies in children co-infected with soil transmitted helminths (STH) (OR: 0.42; 95%CI: 0.28–0.64).When adjusted for age, gender, socio-economic status, nutritional status and geographic location of the children, the risk of P. falciparum infection in children co-infected with STH was higher compared with children who did not have STH infection (OR = 1.3; 95% CI 1.03–1.65).A subset of 16 studies showed that the odds of anaemia were higher in children co-infected with Plasmodium and STH than in children with Plasmodium infection alone (OR = 1.20; 95% CI: 0.59–2.45), and were almost equal in children co-infected with Plasmodium-Schistosoma spp or Plasmodium infection alone (OR = 0.97, 95% CI: 0.30–3.14).

Conclusions/Significance

The current review suggests that prevalence of malaria-helminth co-infection is high in children living in endemic countries. The nature of the interactions between malaria and helminth infection and the impact of the co-infection on anaemia remain inconclusive and may be modulated by the immune responses of the affected children.

The adoption of the One Health approach to improve surveillance of venomous animal injury, vector-borne and zoonotic diseases in Foz do Iguaçu, Brazil

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by André de Souza Leandro, Renata Defante Lopes, Caroline Amaral Martins, Açucena Veleh Rivas, Isaac da Silva, Sandro Roberto Galvão, Rafael Maciel-de-Freitas

Public health institutions with sectorized structure and low integration among field teams, old-fashioned practices such as paper-based storage system, and poorly qualified health agents have limited ability to conduct accurate surveillance and design effective timely interventions. Herein, we describe the steps taken by the Zoonosis Control Center of Foz do Iguaçu (CCZ-Foz) in the last 23 years to move from an archaic and sectorized structure to a modern and timely surveillance program embracing zoonotic diseases, venomous animal injuries, and vector-borne diseases epidemiology under the One Health approach. The full implementation of the One Health approach was based on 5 axes: (1) merging sectorized field teams; (2) adoption of digital solutions; (3) health agents empowerment and permanent capacitation; (4) social mobilization; and (5) active surveys. By doing so, notifications related to zoonotic diseases and venomous animals increased 10 and 21 times, respectively, with no impairment on arbovirus surveillance (major concern in the city). Open sources database (PostgreSQL) and software (QGis) are daily updated and create real-time maps to support timely decisions. The adoption of One Health approach increased preparedness for endemic diseases and reemerging and emerging threats such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

A novel, sequencing-free strategy for the functional characterization of <i>Taenia solium</i> proteomic fingerprint

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Sandra Gomez-Fuentes, Sarah Hernández-de la Fuente, Valeria Morales-Ruiz, Dina López-Recinos, Adrián Guevara-Salinas, María Cristina Parada-Colin, Clara Espitia, Adrián Ochoa-Leyva, Filiberto Sánchez, Nelly Villalobos, Asiel Arce-Sillas, Marisela Hernández, Silvia Ivonne Mora, Gladis Fragoso, Edda Sciutto, Laura Adalid-Peralta

The flatworm Taenia solium causes human and pig cysticercosis. When cysticerci are established in the human central nervous system, they cause neurocysticercosis, a potentially fatal disease. Neurocysticercosis is a persisting public health problem in rural regions of Mexico and other developing countries of Latin America, Asia, and Africa, where the infection is endemic. The great variability observed in the phenotypic and genotypic traits of cysticerci result in a great heterogeneity in the patterns of molecules secreted by them within their host. This work is aimed to identify and characterize cysticercal secretion proteins of T. solium cysticerci obtained from 5 naturally infected pigs from Guerrero, Mexico, using 2D-PAGE proteomic analysis. The isoelectric point (IP) and molecular weight (MW) of the spots were identified using the software ImageMaster 2D Platinum v.7.0. Since most secreted proteins are impossible to identify by mass spectrometry (MS) due to their low concentration in the sample, a novel strategy to predict their sequence was applied. In total, 108 conserved and 186 differential proteins were identified in five cultured cysts. Interestingly, we predicted the sequence of 14 proteins that were common in four out of five cysticercus cultures, which could be used to design vaccines or diagnostic methods for neurocysticercosis. A functional characterization of all sequences was performed using the algorithms SecretomeP, SignalP, and BlastKOALA. We found a possible link between signal transduction pathways in parasite cells and human cancer due to deregulation in signal transduction pathways. Bioinformatics analysis also demonstrated that the parasite release proteins by an exosome-like mechanism, which could be of biological interest.

Performance evaluation of Baermann techniques: The quest for developing a microscopy reference standard for the diagnosis of <i>Strongyloides stercoralis</i>

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Woyneshet Gelaye, Nana Aba Williams, Stella Kepha, Augusto Messa Junior, Pedro Emanuel Fleitas, Helena Marti-Soler, Destaw Damtie, Sissay Menkir, Alejandro J. Krolewiecki, Lisette van Lieshout, Wendemagegn Enbiale, on behalf of the Stopping Transmission of Intestinal Parasites (STOP) project consortium

Background

Soil-transmitted helminths (STH) are common in low and middle income countries where there is lack of access to clean water and sanitation. Effective diagnosis and treatment are essential for the control of STH infections. However, among STH parasites, Strongyloides stercoralis is the most neglected species, both in diagnostics and control strategies. Diagnostic methods cover different approaches, each with different sensitivities and specificities, such as serology, molecular techniques and microscopy based techniques. Of the later, the Baermann technique is the most commonly used procedure. In the literature, several ways have been described to perform the Baermann method, which illustrates the overall lack of a ‘(gold) reference standard’ method for the diagnosis of S. stercoralis infection. In this study we have evaluated the performance of three Baermann techniques in order to improve the reference standard for the microscopic diagnosis of S. stercoralis infection thereby facilitating individual case detection, mapping of the disease and proper evaluation of treatment responses.

Methods/Principal findings

A community based cross sectional study was conducted at Zenzelima, Bahir Dar Zuria Ethiopia. A total of 437 stool samples were collected and analyzed by the following procedures: conventional Baermann (CB), modified Baermann (MB), and modified Baermann with charcoal pre-incubation (MBCI). The diagnostic sensitivity and Negative Predictive Value (NPV) of each technique was calculated using the combination of all the three techniques as a composite reference standard. Our result indicated that larvae of S. stercoralis were detected in 151 (34.6%) stool samples. The prevalence of S. stercoralis infection based on the three diagnostic methods was 9.6%, 8.0%, and 31.3% by CB, MB, and MBCI respectively. The sensitivity and NPV for CB, MB, and MBCI were 26.7% and 70.8%, 22.1% and 69.6%, and 87.0% and 93.2%, respectively. The MBCI showed significant difference (P- value = <0.001) in the sensitivity and NPV values when compared with CB and MB values. The agreement between CB, MB, and MBCI with the composite reference standard was 31.8%, 26.7%, 89.6%, respectively.

Conclusion/Significance

Our results suggest the superior performance of MBCI. It is relatively easy to implement, simple to perform and comparatively cheaper. The CB is by far the commonly used method in routine diagnostic although this technique significantly underestimates the true burden of the disease and thereby contributing to the exclusion of S. stercoralis from the control strategies. Therefore, MBCI is recommended as a routine microscopy-based diagnostic test for S. stercoralis infection, particularly in settings where molecular procedures are not available.

Drugs that target early stages of <i>Onchocerca volvulus</i>: A revisited means to facilitate the elimination goals for onchocerciasis

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Shabnam Jawahar, Nancy Tricoche, Christina A. Bulman, Judy Sakanari, Sara Lustigman

Several issues have been identified with the current programs for the elimination of onchocerciasis that target only transmission by using mass drug administration (MDA) of the drug ivermectin. Alternative and/or complementary treatment regimens as part of a more comprehensive strategy to eliminate onchocerciasis are needed. We posit that the addition of “prophylactic” drugs or therapeutic drugs that can be utilized in a prophylactic strategy to the toolbox of present microfilaricidal drugs and/or future macrofilaricidal treatment regimens will not only improve the chances of meeting the elimination goals but may hasten the time to elimination and also will support achieving a sustained elimination of onchocerciasis. These “prophylactic” drugs will target the infective third- (L3) and fourth-stage (L4) larvae of Onchocerca volvulus and consequently prevent the establishment of new infections not only in uninfected individuals but also in already infected individuals and thus reduce the overall adult worm burden and transmission. Importantly, an effective prophylactic treatment regimen can utilize drugs that are already part of the onchocerciasis elimination program (ivermectin), those being considered for MDA (moxidectin), and/or the potential macrofilaricidal drugs (oxfendazole and emodepside) currently under clinical development. Prophylaxis of onchocerciasis is not a new concept. We present new data showing that these drugs can inhibit L3 molting and/or inhibit motility of L4 at IC50 and IC90 that are covered by the concentration of these drugs in plasma based on the corresponding pharmacological profiles obtained in human clinical trials when these drugs were tested using various doses for the therapeutic treatments of various helminth infections.

Rabies encephalitis in a preschool child following postexposure prophylaxis

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by K. M. Chaitra, Sandeep Ballal, N. R. Ramesh Masthi, D. H. Ashwath Narayana, H. T. Yashodha, Mansi Kumar, Afroza Asiya, Divya Bharathi G., Sanjay S. C.

Author summary: We report a case of rabies encephalitis in a 4½-year-old male child with an exposure to a suspect rabid dog. The child developed rabies 25 days after receiving postexposure prophylaxis. Rabies immunoglobulin (RIG) is currently administered according to body weight. In high-risk exposures over the head and neck, local administration of RIG over and above the body weight depending on the site, size, and severity of exposure may help to prevent rabies death. There is a need for further studies to generate new evidence in this regard.

Effects of <i>Trichinella spiralis</i> and its excretory/secretory products on autophagy of host muscle cells <i>in vivo</i> and <i>in vitro</i>

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Xiaoxiang Hu, Xiaolei Liu, Xue Bai, Li Yang, Jing Ding, Xuemin Jin, Chen Li, Yulu Zhang, Yanfeng Li, Yong Yang, Mingyuan Liu

Trichinella spiralis (T. spiralis) is a widely distributed pathogenic microorganism that causes trichinellosis, a disease that has the potential of causing severe harm to their host. Numerous studies have demonstrated that autophagy can be triggered by microbial infection, such as bacteria, viruses, protozoa, and parasitic helminths. However, it’s still unknown whether autophagy can facilitate host resistance to T. spiralis infection. The present study examined the role of autophagy in striated muscle cell transformation following infection with T. spiralis in BALB/c mice. Transmission electron microscopy (TEM) was used to detect the production of the host diaphragm autophagosome after T. spiralis infection, and changes in the protein and transcriptional levels of autophagic marker proteins were also detected. The significance of autophagy in T. spiralis infection, namely inhibition of T. spiralis growth, was preliminarily evaluated by conducting in vivo experiments using autophagy inhibitors. Besides, we studied the effect of excretory-secretory products (ES) of T. spiralis on autophagy of C2C12 myoblasts. The changes in protein and gene expression levels in autophagy-related pathways in vitro and in vivo were measured as further evidence. The results showed that T. spiralis infection induced autophagy in the host muscle cells. Meanwhile, ES inhibited autophagy of myoblasts in vitro, but this did not affect the cell viability. The upregulation and downregulation of autophagy-related factors in skeletal muscle cells may indicate an adaptive mechanism providing a comfortable niche for the parasite.

Describing fine spatiotemporal dynamics of rat fleas in an insular ecosystem enlightens abiotic drivers of murine typhus incidence in humans

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Annelise Tran, Gildas Le Minter, Elsa Balleydier, Anaïs Etheves, Morgane Laval, Floriane Boucher, Vanina Guernier, Erwan Lagadec, Patrick Mavingui, Eric Cardinale, Pablo Tortosa

Murine typhus is a flea-borne zoonotic disease that has been recently reported on Reunion Island, an oceanic volcanic island located in the Indian Ocean. Five years of survey implemented by the regional public health services have highlighted a strong temporal and spatial structure of the disease in humans, with cases mainly reported during the humid season and restricted to the dry southern and western portions of the island. We explored the environmental component of this zoonosis in an attempt to decipher the drivers of disease transmission. To do so, we used data from a previously published study (599 small mammals and 175 Xenopsylla fleas from 29 sampling sites) in order to model the spatial distribution of rat fleas throughout the island. In addition, we carried out a longitudinal sampling of rats and their ectoparasites over a 12 months period in six study sites (564 rats and 496 Xenopsylla fleas) in order to model the temporal dynamics of flea infestation of rats. Generalized Linear Models and Support Vector Machine classifiers were developed to model the Xenopsylla Genus Flea Index (GFI) from climatic and environmental variables. Results showed that the spatial distribution and the temporal dynamics of fleas, estimated through the GFI variations, are both strongly controlled by abiotic factors: rainfall, temperature and land cover. The models allowed linking flea abundance trends with murine typhus incidence rates. Flea infestation in rats peaked at the end of the dry season, corresponding to hot and dry conditions, before dropping sharply. This peak of maximal flea abundance preceded the annual peak of human murine typhus cases by a few weeks. Altogether, presented data raise novel questions regarding the ecology of rat fleas while developed models contribute to the design of control measures adapted to each micro region of the island with the aim of lowering the incidence of flea-borne diseases.

Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite <i>Schistosoma mansoni</i>

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Holly M. Craven, Riccardo Bonsignore, Vasilis Lenis, Nicolo Santi, Daniel Berrar, Martin Swain, Helen Whiteland, Angela Casini, Karl F. Hoffmann

Schistosomiasis is a neglected tropical disease that currently affects over 250 million individuals worldwide. In the absence of an immunoprophylactic vaccine and the recognition that mono-chemotherapeutic control of schistosomiasis by praziquantel has limitations, new strategies for managing disease burden are urgently needed. A better understanding of schistosome biology could identify previously undocumented areas suitable for the development of novel interventions. Here, for the first time, we detail the presence of G-quadruplexes (G4) and putative quadruplex forming sequences (PQS) within the Schistosoma mansoni genome. We find that G4 are present in both intragenic and intergenic regions of the seven autosomes as well as the sex-defining allosome pair. Amongst intragenic regions, G4 are particularly enriched in 3´ UTR regions. Gene Ontology (GO) term analysis evidenced significant G4 enrichment in the wnt signalling pathway (p<0.05) and PQS oligonucleotides synthetically derived from wnt-related genes resolve into parallel and anti-parallel G4 motifs as elucidated by circular dichroism (CD) spectroscopy. Finally, utilising a single chain anti-G4 antibody called BG4, we confirm the in situ presence of G4 within both adult female and male worm nuclei. These results collectively suggest that G4-targeted compounds could be tested as novel anthelmintic agents and highlights the possibility that G4-stabilizing molecules could be progressed as candidates for the treatment of schistosomiasis.

Point-of-care infrared thermal imaging for differentiating venomous snakebites from non-venomous and dry bites

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Paramasivam Sabitha, Chanaveerappa Bammigatti, Surendran Deepanjali, Bettadpura Shamanna Suryanarayana, Tamilarasu Kadhiravan

Background

Local envenomation following snakebites is accompanied by thermal changes, which could be visualized using infrared imaging. We explored whether infrared thermal imaging could be used to differentiate venomous snakebites from non-venomous and dry bites.

Methods

We prospectively enrolled adult patients with a history of snakebite in the past 24 hours presenting to the emergency of a teaching hospital in southern India. A standardized clinical evaluation for symptoms and signs of envenomation including 20-minute whole-blood clotting test and prothrombin time was performed to assess envenomation status. Infrared thermal imaging was done at enrolment, 6 hours, and 24 hours later using a smartphone-based device under ambient conditions. Processed infrared thermal images were independently interpreted twice by a reference rater and once by three novice raters.

Findings

We studied 89 patients; 60 (67%) of them were male. Median (IQR) time from bite to enrolment was 11 (6.5–15) hours; 21 (24%) patients were enrolled within 6 hours of snakebite. In all, 48 patients had local envenomation with/without systemic envenomation, and 35 patients were classified as non-venomous/dry bites. Envenomation status was unclear in six patients. At enrolment, area of increased temperature around the bite site (Hot spot) was evident on infrared thermal imaging in 45 of the 48 patients with envenomation, while hot spot was evident in only 6 of the 35 patients without envenomation. Presence of hot spot on baseline infrared thermal images had a sensitivity of 93.7% (95% CI 82.8% to 98.7%) and a specificity of 82.9% (66.3% to 93.4%) to differentiate envenomed patients from those without envenomation. Interrater agreement for identifying hot spots was more than substantial (Kappa statistic >0.85), and intrarater agreement was almost perfect (Kappa = 0.93). Paradoxical thermal changes were observed in 14 patients.

Conclusions

Point-of-care infrared thermal imaging could be useful in the early identification of non-venomous and dry snakebites.

Robust COX-2-mediated prostaglandin response may drive arthralgia and bone destruction in patients with chronic inflammation post-chikungunya

PLoS Neglected Tropical Diseases News - 17 February 2021 - 2:00pm

by Yosra Bedoui, Axelle Septembre-Malaterre, Claude Giry, Marie-Christine Jaffar-Bandjee, Jimmy Selambarom, Pascale Guiraud, Philippe Gasque

Patients following infection by chikungunya virus (CHIKV) can suffer for months to years from arthralgia and arthritis. Interestingly, methotrexate (MTX) a major immune-regulatory drug has proved to be of clinical benefit. We have previously shown that CHIKV can persist in the joint of one patient 18 months post-infection and plausibly driving chronic joint inflammation but through ill-characterized mechanisms. We have pursued our investigations and report novel histological and in vitro data arguing for a plausible role of a COX-2-mediated inflammatory response post-CHIKV. In the joint, we found a robust COX-2 staining on endothelial cells, synovial fibroblasts and more prominently on multinucleated giant cells identified as CD11c+ osteoclasts known to be involved in bone destruction. The joint tissue was also strongly stained for CD3, CD8, CD45, CD14, CD68, CD31, CD34, MMP2, and VEGF (but not for NO synthase and two B cell markers). Dendritic cells were rarely detected. Primary human synovial fibroblasts were infected with CHIKV or stimulated either by the synthetic molecule polyriboinosinic:polyribocytidylic acid (PIC) to mimic chronic viral infection or cytokines. First, we found that PIC and CHIKV enhanced mRNA expression of COX-2. We further found that PIC but not CHIKV increased the mRNA levels of cPLA2α and of mPGES-1, two other central enzymes in PGE2 production. IFNβ upregulated cPLA2α and COX-2 transcription levels but failed to modulated mPGES-1 mRNA expression. Moreover, PIC, CHIKV and IFNβ decreased mRNA expression of the PGE2 degrading enzyme 15-PGDH. Interestingly, MTX failed to control the expression of all these enzymes. In sharp contrast, dexamethasone was able to control the capacity of pro-inflammatory cytokines, IL-1β as well as TNFα, to stimulate mRNA levels of cPLA2α, COX-2 and mPGES-1. These original data argue for a concerted action of CHIKV (including viral RNA) and cytokines plausibly released from recruited leukocytes to drive a major COX-2-mediated PGE2 proinflammatory responses to induce viral arthritis.

Role of reptiles and associated arthropods in the epidemiology of rickettsioses: A one health paradigm

PLoS Neglected Tropical Diseases News - 17 February 2021 - 2:00pm

by Jairo Alfonso Mendoza-Roldan, Ranju Ravindran Santhakumari Manoj, Maria Stefania Latrofa, Roberta Iatta, Giada Annoscia, Piero Lovreglio, Angela Stufano, Filipe Dantas-Torres, Bernard Davoust, Younes Laidoudi, Oleg Mediannikov, Domenico Otranto

We assessed the presence of Rickettsia spp., Coxiella burnetii and Anaplasma phagocytophilum in reptiles, their ectoparasites and in questing ticks collected in a nature preserve park in southern Italy, as well as in a peri-urban area in another region. We also investigated the exposure to these pathogens in forestry workers, farmers and livestock breeders living or working in the nature preserve park given the report of anecdotal cases of spotted fever rickettsioses. Rickettsia spp. were molecularly detected in Podarcis muralis and Podarcis siculus lizards (i.e., 3.1%), in Ixodes ricinus (up to 87.5%) and in Neotrombicula autumnalis (up to 8.3%) collected from them as well as in I. ricinus collected from the environment (up to 28.4%). Rickettsia monacensis was the most prevalent species followed by Rickettsia helvetica. An undescribed member of the family Anaplasmataceae was detected in 2.4% and 0.8% of the reptiles and ectoparasites, respectively. Sera from human subjects (n = 50) were serologically screened and antibodies to Rickettsia spp. (n = 4; 8%), C. burnetti (n = 8; 16%) and A. phagocytophilum (n = 11; 22%) were detected. Two ticks collected from two forestry workers were positive for spotted fever group (SFG) rickettsiae. Ixodes ricinus is involved in the transmission of SFG rickettsiae (R. monacensis and R. helvetica) in southern Europe and lizards could play a role in the sylvatic cycle of R. monacensis, as amplifying hosts. Meanwhile, N. autumnalis could be involved in the enzootic cycle of some SFG rickettsiae among these animals. People living or working in the southern Italian nature preserve park investigated are exposed to SFG rickettsiae, C. burnetii and A. phagocytophilum.

Ulcerative skin lesions among children in Cameroon: It is not always Yaws

PLoS Neglected Tropical Diseases News - 16 February 2021 - 2:00pm

by Jean-Philippe Ndzomo Ngono, Serges Tchatchouang, Mireille Victorine Noah Tsanga, Earnest Njih Tabah, Albert Tchualeu, Kingsley Asiedu, Lorenzo Giacani, Sara Eyangoh, Tania Crucitti

Outbreaks of yaws-like ulcerative skin lesions in children are frequently reported in tropical and sub-tropical countries. The origin of these lesions might be primarily traumatic or infectious; in the latter case, Treponema pallidum subspecies pertenue, the yaws agent, and Haemophilus ducreyi, the agent of chancroid, are two of the pathogens commonly associated with the aetiology of skin ulcers. In this work, we investigated the presence of T. p. pertenue and H. ducreyi DNA in skin ulcers in children living in yaws-endemic regions in Cameroon. Skin lesion swabs were collected from children presenting with yaws-suspected skin lesions during three outbreaks, two of which occurred in 2017 and one in 2019. DNA extracted from the swabs was used to amplify three target genes: the human β2-microglobulin gene to confirm proper sample collection and DNA extraction, the polA gene, highly conserved among all subspecies of T. pallidum, and the hddA gene of H. ducreyi. A fourth target, the tprL gene was used to differentiate T. p. pertenue from the other agents of human treponematoses in polA-positive samples. A total of 112 samples were analysed in this study. One sample, negative for β2-microglobulin, was excluded from further analysis. T. p. pertenue was only detected in the samples collected during the first 2017 outbreak (12/74, 16.2%). In contrast, H. ducreyi DNA could be amplified from samples from all three outbreaks (outbreak 1: 27/74, 36.5%; outbreak 2: 17/24, 70.8%; outbreak 3: 11/13, 84.6%). Our results show that H. ducreyi was more frequently associated to skin lesions in the examined children than T. p. pertenue, but also that yaws is still present in Cameroon. These findings strongly advocate for a continuous effort to determine the aetiology of ulcerative skin lesions during these recurring outbreaks, and to inform the planned mass treatment campaigns to eliminate yaws in Cameroon.

Infertility and fecundity loss of <i>Wolbachia</i>-infected <i>Aedes aegypti</i> hatched from quiescent eggs is expected to alter invasion dynamics

PLoS Neglected Tropical Diseases News - 16 February 2021 - 2:00pm

by Meng-Jia Lau, Perran A. Ross, Ary A. Hoffmann

The endosymbiotic bacterium Wolbachia shows viral blocking in its mosquito host, leading to its use in arboviral disease control. Releases with Wolbachia strains wMel and wAlbB infecting Aedes aegypti have taken place in several countries. Mosquito egg survival is a key factor influencing population persistence and this trait is also important when eggs are stored prior to releases. We therefore tested the viability of mosquitoes derived from Wolbachia wMel and wAlbB-infected as well as uninfected eggs after long-term storage under diurnal temperature cycles of 11–19°C and 22–30°C. Eggs stored at 11–19°C had higher hatch proportions than those stored at 22–30°C. Adult Wolbachia density declined when they emerged from eggs stored for longer, which was associated with incomplete cytoplasmic incompatibility (CI) when wMel-infected males were crossed with uninfected females. Females from stored eggs at both temperatures continued to show perfect maternal transmission of Wolbachia, but storage reduced the fecundity of both wMel and wAlbB-infected females relative to uninfected mosquitoes. Furthermore, we found a very strong negative impact of the wAlbB infection on the fertility of females stored at 22–30°C, with almost 80% of females hatching after 11 weeks of storage being infertile. Our findings provide guidance for storing Wolbachia-infected A. aegypti eggs to ensure high fitness adult mosquitoes for release. Importantly, they also highlight the likely impact of egg quiescence on the population dynamics of Wolbachia-infected populations in the field, and the potential for Wolbachia to suppress mosquito populations through cumulative fitness costs across warm and dry periods, with expected effects on dengue transmission.

Heterogeneity in response to serological exposure markers of recent <i>Plasmodium vivax</i> infections in contrasting epidemiological contexts

PLoS Neglected Tropical Diseases News - 16 February 2021 - 2:00pm

by Jason Rosado, Michael T. White, Rhea J. Longley, Marcus Lacerda, Wuelton Monteiro, Jessica Brewster, Jetsumon Sattabongkot, Mitchel Guzman-Guzman, Alejandro Llanos-Cuentas, Joseph M. Vinetz, Dionicia Gamboa, Ivo Mueller

Background

Antibody responses as serological markers of Plasmodium vivax infection have been shown to correlate with exposure, but little is known about the other factors that affect antibody responses in naturally infected people from endemic settings. To address this question, we studied IgG responses to novel serological exposure markers (SEMs) of P. vivax in three settings with different transmission intensity.

Methodology

We validated a panel of 34 SEMs in a Peruvian cohort with up to three years’ longitudinal follow-up using a multiplex platform and compared results to data from cohorts in Thailand and Brazil. Linear regression models were used to characterize the association between antibody responses and age, the number of detected blood-stage infections during follow-up, and time since previous infection. Receiver Operating Characteristic (ROC) analysis was used to test the performance of SEMs to identify P. vivax infections in the previous 9 months.

Principal findings

Antibody titers were associated with age, the number of blood-stage infections, and time since previous P. vivax infection in all three study sites. The association between antibody titers and time since previous P. vivax infection was stronger in the low transmission settings of Thailand and Brazil compared to the higher transmission setting in Peru. Of the SEMs tested, antibody responses to RBP2b had the highest performance for classifying recent exposure in all sites, with area under the ROC curve (AUC) = 0.83 in Thailand, AUC = 0.79 in Brazil, and AUC = 0.68 in Peru.

Conclusions

In low transmission settings, P. vivax SEMs can accurately identify individuals with recent blood-stage infections. In higher transmission settings, the accuracy of this approach diminishes substantially. We recommend using P. vivax SEMs in low transmission settings pursuing malaria elimination, but they are likely to be less effective in high transmission settings focused on malaria control.

Examining the Ugandan health system’s readiness to deliver rheumatic heart disease-related services

PLoS Neglected Tropical Diseases News - 16 February 2021 - 2:00pm

by Emma Ndagire, Yoshito Kawakatsu, Hadija Nalubwama, Jenifer Atala, Rachel Sarnacki, Jafesi Pulle, Rakeli Kyarimpa, Rachel Mwima, Rosemary Kansiime, Emmy Okello, Peter Lwabi, Andrea Beaton, Craig Sable, David Watkins

Background

In 2018, the World Health Assembly mandated Member States to take action on rheumatic heart disease (RHD), which persists in countries with weak health systems. We conducted an assessment of the current state of RHD-related healthcare in Uganda.

Methodology/Principal findings

This was a mixed-methods, deductive simultaneous design study conducted in four districts of Uganda. Using census sampling, we surveyed health facilities in each district using an RHD survey instrument that was modeled after the WHO SARA tool. We interviewed health workers with experience managing RHD, purposively sampling to ensure a range of qualification and geographic variation. Our final sample included 402 facilities and 36 health workers. We found major gaps in knowledge of clinical guidelines and availability of diagnostic tests. Antibiotics used in RHD prevention were widely available, but cardiovascular medications were scarce. Higher levels of service readiness were found among facilities in the western region (Mbarara district) and private facilities. Level III health centers were the most prepared for delivering secondary prevention. Health worker interviews revealed that limited awareness of RHD at the district level, lack of diagnostic tests and case management registries, and absence of clearly articulated RHD policies and budget prioritization were the main barriers to providing RHD-related healthcare.

Conclusions/Significance

Uganda’s readiness to implement the World Health Assembly RHD Resolution is low. The forthcoming national RHD strategy must focus on decentralizing RHD diagnosis and prevention to the district level, emphasizing specialized training of the primary healthcare workforce and strengthening supply chains of diagnostics and essential medicines.

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