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Comorbidities associated with non- healing of plantar ulcers in leprosy patients

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

by Brahmaiah Upputuri, Aparna Srikantam, Raja Sriswan Mamidi

Background

Non-healing plantar ulcers are one of the significant causes of disability in leprosy patients. Plantar ulcers often take months or years to heal, affecting the patient’s quality of life. Presence of comorbid conditions in these patients can delay wound healing. The study aimed to evaluate the role of associated comorbid conditions as risk factors in ulcer healing.

Methodology/Principal findings

A total of 66 leprosy patients with plantar ulcers registered at LEPRA Society-Blue Peter Public Health and Research Center (BPHRC), Hyderabad, India from June 2018 to June 2019 were studied. Comprehensive clinical assessment was done, including screening for comorbid conditions and treated as per the recommended guidelines. About two-thirds of the participants were aged 50 and above, of which more than half were illiterates, and 93.5% were living below the poverty line. Majority of ulcers were seen on the forefoot; with the head of meta-tarsal bone 27 (41.6%) as the commonest site, followed by calcaneum 23 (38.3%) and great toe 10 (16.6%). Mean ulcer depth was 0.61 (0.57) cm, the area was 5.24 (6.73) cm2 and ulcer volume was 4.72 (14.33) cm3. Ulcer dimensions were significantly associated with low body mass index, hypertension and smoking.

Conclusions/Significance

Identifying the risk factors delaying wound healing and detailed assessment of ulcers are of profound importance to predict the outcome of plantar ulcers in leprosy patients. The study findings indicate the need for better policies by the leprosy control program for the comprehensive management of plantar ulcers.

Liver fluke infections by <i>Amphimerus</i> sp. (Digenea: Opisthorchiidae) in definitive and fish intermediate hosts in Manabí province, Ecuador

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

by Daniel Romero-Alvarez, Gabriela Valverde-Muñoz, Manuel Calvopina, Maira Rojas, William Cevallos, Hideo Kumazawa, Hidekazu Takagi, Hiromu Sugiyama

Amphimerus sp. is a fluke that dwells in the biliary tracts of vertebrate definitive hosts including humans, domestic, and wild mammals in Latin America. Opisthorchiid liver infections are rarely studied in the Americas confirming its status as a neglected tropical disease. In Ecuador, small trematode eggs were reported in human cases from the province of Manabí in 1949, and recently, Amphimerus sp. adults were recovered from human and reservoir hosts in the province of Esmeraldas. Due to the lack of research on the infectious sources of Amphimerus sp. in the continent, we have developed a series of epidemiological studies with parasitological and molecular techniques to elucidate the endemicity of opisthorchiid fluke infections in Manabí, Ecuador. We developed a cross-sectional study in three communities at Pedro Pablo Gómez parish in the province of Manabí, Ecuador. We examined a total of 176 fecal samples to detect opisthorchiid eggs, and four fish species to find opisthorchiid metacercariae. To study adult worms, we treated and purged seven patients in a family and dissected the livers of a dog and a cat infected. We observed morphological features of adults and metacercariae and used polymerase chain reaction with restricted fragment length polymorphism (PCR-RFLP) and DNA sequencing of a section of the ITS2 gene for identification. Small trematode eggs were detected in 63 (35.8%) out of 176 fecal samples of residents in the three study sites. Adult opisthorchiid flukes were recovered from human patients, a dog and a cat, and they were morphologically and molecularly identified as Amphimerus sp. Opisthorchiid metacercariae were also identified molecularly as Amphimerus sp. in four fish species, i.e., Rhoadsia altipinna, Bryconamericus bucay, Andinoacara rivulatus, and Piabucina aureoguttata. Metacercariae of the heterophyid Haplorchis pumilio were also found in the four fish species examined. This is the first study to confirm the current endemicity of Amphimerus sp. in Pedro Pablo Gómez, Manabí, Ecuador. The adult worms isolated here shared morphological characteristics with previous Amphimerus sp. descriptions and were molecularly similar to Amphimerus sp. described in the neighboring province of Esmeraldas. Moreover, this study is the first to document four fish species as infection sources of Amphimerus sp. detected via a molecular protocol targeting the metacercariae of the parasite. Fish species identified here should be targeted for public health campaigns to avoid further human liver-fluke infections by Amphimerus sp. or potential intestinal-fluke infections by H. pumilio or others.

Genetic diversity and phylogenetic analysis of Crimean-Congo Hemorrhagic Fever viruses circulating in Pakistan during 2019

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

by Massab Umair, Adnan Khurshid, Muhammad Masroor Alam, Ribqa Akhtar, Muhammad Salman, Aamer Ikram

Being an endemic country for Crimean Congo hemorrhagic fever (CCHF), this study aimed to explore the genetic diversity of CCHF virus (CCHFV) detected in Pakistan during 2019. Serum samples from patients with clinical signs of hemorrhagic fever attending tertiary care hospitals in Pakistan were tested for CCHFV RNA using real-time PCR at Department of Virology, National Institute of Health. The partial S-gene fragments were directly sequenced to determine the prevailing CCHFV genotypes and their molecular epidemiology in Pakistan. During January-December 2019, 280 samples from suspected CCHF patients were tested and 28 (10%) were found positive on real-time PCR. Positive cases were detected from 14 districts and across all four provinces of Pakistan with majority reported during August-September. The mean age of CCHFV positive patients was 37.25 years (range 5–65 years) with a high frequency in males (92.8%; n = 26) and a case fatality rate of 40.7% was observed. Phylogenetic analysis showed that S- segment of 2019 PAK CCHFV strains (n = 13) belonged to Asia-1 genotype and clustered with regional strains from Iran, Oman, and Afghanistan. We conclude that Asia-1 genotype of CCHF virus remains endemic in Pakistan. Our findings emphasize to establish a laboratory based surveillance program to monitor the disease burden and identify outbreak hotspots for effective control.

Abortive vampire bat rabies infections in Peruvian peridomestic livestock

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

by Julio A. Benavides, Andres Velasco-Villa, Lauren C. Godino, Panayampalli Subbian Satheshkumar, Nino Ruby, Elizabeth Rojas-Paniagua, Carlos Shiva, Nestor Falcon, Daniel G. Streicker

Rabies virus infections normally cause universally lethal encephalitis across mammals. However, ‘abortive infections’ which are resolved prior to the onset of lethal disease have been described in bats and a variety of non-reservoir species. Here, we surveyed rabies virus neutralizing antibody titers in 332 unvaccinated livestock of 5 species from a vampire bat rabies endemic region of southern Peru where livestock are the main food source for bats. We detected rabies virus neutralizing antibody titers in 11, 5 and 3.6% of cows, goats and sheep respectively and seropositive animals did not die from rabies within two years after sampling. Seroprevalence was correlated with the number of local livestock rabies mortalities reported one year prior but also one year after sample collection. This suggests that serological status of livestock can indicate the past and future levels of rabies risk to non-reservoir hosts. To our knowledge, this is the first report of anti-rabies antibodies among goats and sheep, suggesting widespread abortive infections among livestock in vampire bat rabies endemic areas. Future research should resolve the within-host biology underlying clearance of rabies infections. Cost-effectiveness analyses are also needed to evaluate whether serological monitoring of livestock can be a viable complement to current monitoring of vampire bat rabies risk based on animal mortalities alone.

A randomized controlled trial comparing the effectiveness of individual versus household treatment for Scabies in Lambaréné, Gabon

PLoS Neglected Tropical Diseases News - 26 June 2020 - 9:00pm

by Julian Matthewman, Rella Zoleko Manego, Lia Betty Dimessa Mbadinga, Hana Šinkovec, Katrin Völker, Malik Akinosho, Christian Haedrich, Jeanne Tardif d’Hamonville, Bertrand Lell, Ayola Akim Adegnika, Michael Ramharter, Ghyslain Mombo-Ngoma

Background

It is unclear whether individual treatment of scabies is similarly effective compared to household treatment. This study compared these two treatment strategies with topical benzyl benzoate for treating scabies in Lambaréné, Gabon.

Methods

Participants presenting with uncomplicated scabies were randomized into either the Individual Treatment group, where only the affected participants received treatment, or the Household Treatment group, where all family members were treated in parallel to the affected participants regardless of signs and symptoms. The primary endpoint was clinical cure after 28 days; the secondary endpoint was the proportion of affected household members per household after 28 days.

Results

After 28 days, from a total of 79 participants assessed, 67% (n = 53) were clinically cured; 59% (20/34) in the Individual Treatment group and 73% (33/45) in the Household Treatment group. Participants in the Household Treatment group had about twice the odds of being cured (odds ratio 1.9, 95% confidence interval: 0.8–4.9; p = 0.17). For the secondary outcome, an effect of similar size was observed.

Conclusions

Our findings show that treating close contacts of persons affected by scabies may be beneficial to patients and contacts, however, the benefit was less pronounced than anticipated and further research is needed to definitively answer this question.

<i>T</i>. <i>brucei</i> infections abrogate diverse plasma cell-mediated effector B cell responses, independently of their specificity, affinity and host genetic background

PLoS Neglected Tropical Diseases News - 26 June 2020 - 9:00pm

by Carl De Trez, Shahid Khan, Stefan Magez

Antibody-mediated parasite killing is considered the most effective host immune response against extracellular trypanosome parasites. However, due to host-parasite co-evolution pressure, these parasites have “learned” how to hijack the host immune system via the development of immune evasion strategies. Hereby they prevent elimination and promote transmission. In the past, our group has shown that African trypanosome parasites are able to “shut down” the host B cell compartment, via the abolishment of the homeostatic B cell compartment. In line with this, we have reported that trypanosome infections result in detrimental outcomes on auto-reactive and cancer B cells. To unravel the immune mechanisms involved in these processes we adopted here a well-defined B cell vaccine model, i.e. the thymo-dependent hapten-carrier NP-CGG (4-Hydroxy-3-nitrophenylacetyl-Chicken Gamma Globulin) emulsified in Alum adjuvant. Results show that T. brucei infections abrogate the circulating titres of vaccine-induced CGG-specific as well as NP-specific IgG1+ antibodies, a hallmark of memory B cell responses in this model. This happens independently of their affinity and IFNɣ signalling. Next, we demonstrate that T. brucei infections also induce a decrease of anti-NP IgG3+ antibodies induced by the administration of NP coupled to Ficoll, a thymo-independent antigen. Confirming the non-specificity of the infection-associated immunopathology, this report also shows that trypanosome infections abolish vaccine-induced memory response against malaria parasite in BALB/c mice. Together, these data indicates that T. brucei infections impair every stages of B cell development, including effector plasma B cells, independently of their specificity and affinity as well as the host genetic background.

Development of an ELISA for the quantification of mycolactone, the cytotoxic macrolide toxin of <i>Mycobacterium ulcerans</i>

PLoS Neglected Tropical Diseases News - 26 June 2020 - 9:00pm

by Louisa Warryn, Jean-Pierre Dangy, Philipp Gersbach, Matthias Gehringer, Anja Schäfer, Marie-Thérèse Ruf, Nicolas Ruggli, Karl-Heinz Altmann, Gerd Pluschke

Mycolactones, macrolide cytotoxins, are key virulence factors of Mycobacterium ulcerans, the etiological agent of the chronic necrotizing skin disease Buruli ulcer. There is urgent need for a simple point-of-care laboratory test for Buruli ulcer and mycolactone represents a promising target for the development of an immunological assay. However, for a long time, all efforts to generate mycolactone-specific antibodies have failed. By using a protein conjugate of a truncated non-toxic synthetic mycolactone derivative, we recently described generation of a set of mycolactone-specific monoclonal antibodies. Using the first mycolactone-specific monoclonal antibodies that we have described before, we were able to develop an antigen competition assay that detects mycolactones. By the systematic selection of a capturing antibody and a reporter molecule, and the optimization of assay conditions, we developed an ELISA that detects common natural variants of mycolactone with a limit of detection in the low nanomolar range. The mycolactone-specific ELISA described here will be a very useful tool for research on the biology of this macrolide toxin. After conversion into a simple point-of-care test format, the competition assay may have great potential as laboratory assay for both the diagnosis of Buruli ulcer and for the monitoring of treatment efficacy.

Expansions of chemosensory gene orthologs among selected tsetse fly species and their expressions in <i>Glossina morsitans morsitans</i> tsetse fly

PLoS Neglected Tropical Diseases News - 26 June 2020 - 9:00pm

by Joy M. Kabaka, Benson M. Wachira, Clarence M. Mang’era, Martin K. Rono, Ahmed Hassanali, Sylvance O. Okoth, Vincent O. Oduol, Rosaline W. Macharia, Grace A. Murilla, Paul O. Mireji

Tsetse fly exhibit species-specific olfactory uniqueness potentially underpinned by differences in their chemosensory protein repertoire. We assessed 1) expansions of chemosensory protein orthologs in Glossina morsitans morsitans, Glossina pallidipes, Glossina austeni, Glossina palpalis gambiensis, Glossina fuscipes fuscipes and Glossina brevipalpis tsetse fly species using Café analysis (to identify species-specific expansions) and 2) differential expressions of the orthologs and associated proteins in male G. m. morsitans antennae and head tissues using RNA-Seq approaches (to establish associated functional molecular pathways). We established accelerated and significant (P<0.05, λ = 2.60452e-7) expansions of gene families in G. m. morsitans (Odorant receptor (Or)71a, Or46a, Ir75a,d, Ionotropic receptor (Ir) 31a, Ir84a, Ir64a and Odorant binding protein (Obp) 83a-b), G. pallidipes (Or67a,c, Or49a, Or92a, Or85b-c,f and Obp73a), G. f. fuscipes (Ir21a, Gustatory receptor (Gr) 21a and Gr63a), G. p. gambiensis (clumsy, Ir25a and Ir8a) and G. brevipalpis (Ir68a) and missing orthologs in each tsetse fly species. Most abundantly expressed transcripts in male G. m. morsitans included specific Or (Orco, Or56a, 65a-c, Or47b, Or67b, GMOY012254, GMOY009475, and GMOY006265), Grs (Gr21a, Gr63a, GMOY013297 and GMOY013298), Ir (Ir8a, Ir25a and Ir41a) and Obp (Obp19a, lush, Obp28a, Obp83a-b Obp44a, GMOY012275 and GMOY013254) orthologs. Most enriched biological processes in the head were associated with vision, muscle activity and neuropeptide regulations, amino acid/nucleotide metabolism and circulatory system processes. Antennal enrichments (>90% of chemosensory transcripts) included cilium-associated mechanoreceptors, chemo-sensation, neuronal controlled growth/differentiation and regeneration/responses to stress. The expanded and tsetse fly species specific orthologs includes those associated with known tsetse fly responsive ligands (4-methyl phenol, 4-propyl phenol, acetic acid, butanol and carbon dioxide) and potential tsetse fly species-specific responsive ligands (2-oxopentanoic acid, phenylacetaldehyde, hydroxycinnamic acid, 2-heptanone, caffeine, geosmin, DEET and (cVA) pheromone). Some of the orthologs can potentially modulate several tsetse fly species-specific behavioral (male-male courtship, hunger/host seeking, cool avoidance, hygrosensory and feeding) phenotypes. The putative tsetse fly specific chemosensory gene orthologs and their respective ligands provide candidate gene targets and kairomones for respective downstream functional genomic and field evaluations that can effectively expand toolbox of species-specific tsetse fly attractants, repellents and other tsetse fly behavioral modulators.

Snakebite epidemiology and health-seeking behavior in Akonolinga health district, Cameroon: Cross-sectional study

PLoS Neglected Tropical Diseases News - 25 June 2020 - 9:00pm

by Gabriel Alcoba, Manon Chabloz, Justin Eyong, Franck Wanda, Carlos Ochoa, Eric Comte, Armand Nkwescheu, François Chappuis

Background

Snakebite envenoming causes 81,000–138,000 annual human deaths and pain, terror, or disability in 4.5–5.4 million victims. Accurate community-based epidemiological data is scarce. Our objective was to assess snakebite incidence, mortality, and health-seeking behavior, in an affected health district of Cameroon.

Methods

We conducted a cross-sectional multicluster household survey in Akonolinga health district, Centre Region, Cameroon, from October to December 2016. Using probability-proportional-to-size, 20 villages were randomly selected, then, all inhabited households were systematically selected. Annual incidence and adjusted odds-ratio for predictors were estimated.

Findings

Among the 9,924 participants, 66 suffered a snakebite during the past year: the resulting incidence is 665 (95%CI: 519–841) per 100,000 inhabitants per year. Victims were aged 5-75y (median: 34y), 53% were male and 57% farmer-cultivators. Two children died (case-fatality rate: 3%); 39 (59%) presented severity signs, including 2 (3%) neurotoxic syndromes, 20 (30%) systemic digestive syndromes, and 17 (26%) severe cytotoxic syndromes. Non-severe cases included 20 (30%) mild cytotoxic syndromes and 7 (11%) dry bites. Only two victims (3%) received antivenom. 59 (89%) used family traditional practices, 25 (38%) traditional healers, and 31 (47%) consulted health facilities. Median delays to these three care-options were 5, 45, and 60 minutes, respectively. Traditional treatments included incisions (n = 57; 86%), tourniquets (n = 51; 77%) and black-stones (n = 44; 67%). The two last procedures were also used in health facilities (n = 18). Consulting traditional healers was associated with severity (adjusted-OR: 19.6 (2.5–156), p = 0.005) and complications (aOR: 17.3, 2.4–123, p = 0.004). Long-term disabilities were subjective psychological trauma (n = 47; 71%), finger amputation (n = 1; 2%), ankylosis (n = 1; 2%) and chronic pain (n = 1; 2%).

Conclusions

We observed alarming levels of snakebite incidence, mortality, antivenom scarcity, and use of traditional medicine. It could represent several thousands of victims at national level. We suggested conducting a country-wide study, and improving antivenom supply, first-aid training, for traditional healers and health professionals.

The health beliefs, dengue knowledge and control behaviors among internally displaced persons versus local residents in Kachin Special Region II, Myanmar

PLoS Neglected Tropical Diseases News - 25 June 2020 - 9:00pm

by Jian-Wei Xu, Hui Liu, Bi Yaw, Hkawn Shawng Nbwi

Dengue fever (DF) is one of main public health problems along the China-Myanmar border, however, data about DF is still lacking in Kachin Special Region II (KSR2), Myanmar. To understand health beliefs in general, and knowledge and treatment-seeking and prevention behaviors related to DF among the neglected population, the study was carried out by using a combination of quantitative household questionnaire surveys (HHSs) and qualitative semi-structured in-depth interviews (SDIs). The HHS questionnaire was administered to a total of 258 household heads. The 215 (83.3%) HHS respondents believed in Christianity and Catholicism. However, the 141 (54.7%,) of the total respondents thought that people with evil practices might be punished by diseases. More respondents believed that too rainy weather and water were more related to disease in the internally displaced person (IDP) camp than the local community (P<0.01). Most of the HHS respondents had sound knowledge of dengue symptoms, causes, vectors, transmission and prevention. The 257 (99.6%) HHS respondents reported that their families went to the public health facilities first to seek treatment. The 210 (84.1%) respondents reported that they turned containers upside down within five days. The key informants (n = 18) identified that the appropriate knowledge and behaviors were attributable to formal school education and specific health education campaign during the outbreak response in 2017, and that Kachin people enjoy conversing with each other, neighbors talked about the dengue information they received. The study results indicated that Kachin people have a good knowledge and behaviors of dengue control. The actual situation of dengue is still not clear due to lacking data of laboratory test. In the context of resources shortage, more international assistance is still needed to promote local dengue control and prevention efforts.

The safety profile of favipiravir should not be the first argument to suspend its evaluation in viral hemorrhagic fevers

PLoS Neglected Tropical Diseases News - 25 June 2020 - 9:00pm

by Denis Malvy, Anne-Marie Taburet, Xavier de Lamballerie, France Mentre, Fabrice Extramiana

An interactive database for the investigation of high-density peptide microarray guided interaction patterns and antivenom cross-reactivity

PLoS Neglected Tropical Diseases News - 24 June 2020 - 9:00pm

by Kamille E. Krause, Timothy P. Jenkins, Carina Skaarup, Mikael Engmark, Nicholas R. Casewell, Stuart Ainsworth, Bruno Lomonte, Julián Fernández, José M. Gutiérrez, Ole Lund, Andreas H. Laustsen

Snakebite envenoming is a major neglected tropical disease that affects millions of people every year. The only effective treatment against snakebite envenoming consists of unspecified cocktails of polyclonal antibodies purified from the plasma of immunized production animals. Currently, little data exists on the molecular interactions between venom-toxin epitopes and antivenom-antibody paratopes. To address this issue, high-density peptide microarray (hdpm) technology has recently been adapted to the field of toxinology. However, analysis of such valuable datasets requires expert understanding and, thus, complicates its broad application within the field. In the present study, we developed a user-friendly, and high-throughput web application named “Snake Toxin and Antivenom Binding Profiles” (STAB Profiles), to allow straight-forward analysis of hdpm datasets. To test our tool and evaluate its performance with a large dataset, we conducted hdpm assays using all African snake toxin protein sequences available in the UniProt database at the time of study design, together with eight commercial antivenoms in clinical use in Africa, thus representing the largest venom-antivenom dataset to date. Furthermore, we introduced a novel method for evaluating raw signals from a peptide microarray experiment and a data normalization protocol enabling intra-microarray and even inter-microarray chip comparisons. Finally, these data, alongside all the data from previous similar studies by Engmark et al., were preprocessed according to our newly developed protocol and made publicly available for download through the STAB Profiles web application (http://tropicalpharmacology.com/tools/stab-profiles/). With these data and our tool, we were able to gain key insights into toxin-antivenom interactions and were able to differentiate the ability of different antivenoms to interact with certain toxins of interest. The data, as well as the web application, we present in this article should be of significant value to the venom-antivenom research community. Knowledge gained from our current and future analyses of this dataset carry the potential to guide the improvement and optimization of current antivenoms for maximum patient benefit, as well as aid the development of next-generation antivenoms.

Serotype-specific detection of dengue viruses in a nonstructural protein 1-based enzyme-linked immunosorbent assay validated with a multi-national cohort

PLoS Neglected Tropical Diseases News - 24 June 2020 - 9:00pm

by Irene Bosch, Ankita Reddy, Helena de Puig, Juan E. Ludert, Federico Perdomo-Celis, Carlos F. Narváez, Alice Versiani, Diana Fandos, Mauricio L. Nogueira, Mohit Singla, Rakesh Lodha, Guruprasad R. Medigeshi, Ivette Lorenzana, Hugo Vicente Ralde, Margarita Gélvez-Ramírez, Luis A. Villar, Megan Hiley, Laura Mendoza, Nol Salcedo, Bobby Brooke Herrera, Lee Gehrke

Background

Dengue virus (DENV) infections pose one of the largest global barriers to human health. The four serotypes (DENV 1–4) present different symptoms and influence immune response to subsequent DENV infections, rendering surveillance, risk assessments, and disease control particularly challenging. Early diagnosis and appropriate clinical management is critical and can be achieved by detecting DENV nonstructural protein 1 (NS1) in serum during the acute phase. However, few NS1-based tests have been developed that are capable of differentiating DENV serotypes and none are currently commercially available.

Methodology/Principle findings

We developed an enzyme-linked immunosorbent assay (ELISA) to distinguish DENV-1-4 NS1 using serotype-specific pairs of monoclonal antibodies. A total of 1,046 antibodies were harvested from DENV-immunized mice and screened for antigen binding affinity. ELISA clinical performance was evaluated using 408 polymerase chain reaction-confirmed dengue samples obtained from patients in Brazil, Honduras, and India. The overall sensitivity of the test for pan-DENV was 79.66% (325/408), and the sensitivities for DENV-1-4 serotyping were 79.1% (38/48), 80.41% (78/97), 100% (45/45), and 79.6% (98/123), respectively. Specificity reached 94.07–100%.

Significance

Our study demonstrates a robust antibody screening strategy that enabled the development of a serotype NS1-based ELISA with maximized specific and sensitive antigen binding. This sensitive and specific assay also utilized the most expansive cohort to date, and of which about half are from Latin America, a geographic region severely underrepresented in previous similar studies. This ELISA test offers potential enhanced diagnostics during the acute phase of infection to help guide patient care and disease control. These results indicate that this ELISA is a promising aid in early DENV-1-4 diagnosis and surveillance in regions of endemicity in addition to offer convenient monitoring for future vaccine interventions.

Monitoring of alien mosquitoes in Western Austria (Tyrol, Austria, 2018)

PLoS Neglected Tropical Diseases News - 23 June 2020 - 9:00pm

by Hans-Peter Fuehrer, Ellen Schoener, Stefanie Weiler, Bita Shahi Barogh, Carina Zittra, Gernot Walder

Mosquitoes are of major importance to human and animal health due to their ability to transmit various pathogens. In Europe the role of mosquitoes in public health has increased with the introduction of alien Aedes mosquitoes such as the Asian tiger mosquito, Aedes albopictus; the Asian bush mosquito, Ae. japonicus; and Ae. koreicus. In Austria, Ae. japonicus has established populations in various regions of the country. Aedes albopictus is not known to overwinter in Austria, although isolated findings of eggs and adult female mosquitoes have been previously reported, especially in Tyrol. Aedes koreicus had not so far been found in Austria. Within the framework of an alien mosquito surveillance program in the Austrian province of Tyrol, ovitraps were set up weekly from May to October, 2018, at 67 sites– 17 in East Tyrol and 50 in North Tyrol. Sampling was performed at highways and at urban and rural areas. DNA obtained from mosquito eggs was barcoded using molecular techniques and sequences were analysed to species level. Eggs of alien Aedes species were found at 18 out of 67 sites (27%). Both Ae. albopictus and Ae. japonicus were documented at highways and urban areas in both East and North Tyrol. Aedes koreicus was found in East Tyrol. During this mosquito surveillance program, eggs of Ae. albopictus, Ae. japonicus, and Ae. koreicus were documented in the Austrian province of Tyrol. These findings not only show highways to be points of entry, but also point to possible establishment processes of Ae. japonicus in Tyrol. Moreover, Ae. koreicus was documented in Austria for the first time.

CXCR3 chemokine receptor contributes to specific CD8<sup>+</sup> T cell activation by pDC during infection with intracellular pathogens

PLoS Neglected Tropical Diseases News - 23 June 2020 - 9:00pm

by Camila Pontes Ferreira, Leonardo de Moro Cariste, Isaú Henrique Noronha, Danielle Fernandes Durso, Joseli Lannes-Vieira, Karina Ramalho Bortoluci, Daniel Araki Ribeiro, Douglas Golenbock, Ricardo Tostes Gazzinelli, José Ronnie Carvalho de Vasconcelos

Chemokine receptor type 3 (CXCR3) plays an important role in CD8+ T cells migration during intracellular infections, such as Trypanosoma cruzi. In addition to chemotaxis, CXCR3 receptor has been described as important to the interaction between antigen-presenting cells and effector cells. We hypothesized that CXCR3 is fundamental to T. cruzi-specific CD8+ T cell activation, migration and effector function. Anti-CXCR3 neutralizing antibody administration to acutely T. cruzi-infected mice decreased the number of specific CD8+ T cells in the spleen, and those cells had impaired in activation and cytokine production but unaltered proliferative response. In addition, anti-CXCR3-treated mice showed decreased frequency of CD8+ T cells in the heart and numbers of plasmacytoid dendritic cells in spleen and lymph node. As CD8+ T cells interacted with plasmacytoid dendritic cells during infection by T. cruzi, we suggest that anti-CXCR3 treatment lowers the quantity of plasmacytoid dendritic cells, which may contribute to impair the prime of CD8+ T cells. Understanding which molecules and mechanisms guide CD8+ T cell activation and migration might be a key to vaccine development against Chagas disease as those cells play an important role in T. cruzi infection control.

Growth velocity in children with Environmental Enteric Dysfunction is associated with specific bacterial and viral taxa of the gastrointestinal tract in Malawian children

PLoS Neglected Tropical Diseases News - 23 June 2020 - 9:00pm

by Chandni Desai, Scott A. Handley, Rachel Rodgers, Cynthia Rodriguez, Maria I. Ordiz, Mark J. Manary, Lori R. Holtz

Environmental enteric dysfunction (EED) is characterized by diffuse villous atrophy of the small bowel. EED is strongly associated with stunting, a major public health problem linked to increased childhood morbidity and mortality. EED and subsequent stunting of linear growth are surmised to have microbial origins. To interrogate this relationship, we defined the comprehensive virome (eukaryotic virus and bacteriophage) and bacterial microbiome of a longitudinal cohort of rural Malawian children with extensive metadata and intestinal permeability testing at each time point. We found thirty bacterial taxa differentially associated with linear growth. We detected many eukaryotic viruses. Neither the total number of eukaryotic families nor a specific viral family was statistically associated with improved linear growth. We identified 3 differentially abundant bacteriophage among growth velocities. Interestingly, there was a positive correlation between bacteria and bacteriophage richness in children with subsequent adequate/moderate growth which children with subsequent poor growth lacked. This suggests that a disruption in the equilibrium between bacteria and bacteriophage communities might be associated with subsequent poor growth. Future studies of EED and stunting should include the evaluation of viral communities in addition to bacterial microbiota to understand the complete microbial ecology of these poorly understood entities.

The impact of four years of semiannual treatments with albendazole alone on lymphatic filariasis and soil-transmitted helminth infections: A community-based study in the Democratic Republic of the Congo

PLoS Neglected Tropical Diseases News - 23 June 2020 - 9:00pm

by Sébastien D. S. Pion, Cédric B. Chesnais, Naomi P. Awaca-Uvon, Johnny Vlaminck, Anlimou Abdou, Billy Kunyu-Shako, Godefroy Kuyangisa Simuna, Jean-Paul Tambwe, Gary J. Weil, Michel Boussinesq

Background

The World Health Organization now recommends semiannual mass drug administration (MDA) of albendazole with integrated vector management as an option for eliminating lymphatic filariasis (LF) in areas of loiasis-endemic countries where it may not be safe to use diethylcarbamazine or ivermectin in MDA programs. However, the published evidence base to support this policy is thin, and uptake by national programs has been slow.

Methodology/Principal findings

We conducted a community trial to assess the impact of semiannual MDA on lymphatic filariasis and soil-transmitted helminth infections (STH) in two villages in the Bandundu province of the Democratic Republic of the Congo with moderately high prevalences for LF and hookworm infections. MDA with albendazole was provided every six months from June 2014 to December 2017 with treatment coverages of the eligible population (all ≥ 2 year of age) that ranged between 56% and 88%. No adverse effects were reported during the trial. Evaluation at 48 months, (i.e. 6 months after the 8th round of MDA), showed that W. bancrofti microfilaremia (Mf) prevalence in the study communities had decreased between 2014 to 2018 from 12% to 0.9% (p<0.001). The prevalence of W. bancrofti antigenemia was also significantly reduced from 31.6% to 8.5% (p<0.001). MDA with albendazole also reduced hookworm, Ascaris lumbricoides and Trichuris trichiura infection prevalences in the community from 58.6% to 21.2% (p<0.001), from 14.0% to 1.6% and 4.1% to 2.9%, respectively. Hookworm and Ascaris infection intensities were reduced by 93% (p = 0.02) and 57% (p = 0.03), respectively. In contrast, Trichuris infection intensity was not significantly reduced by MDA (p = 0.61) over this time period.

Conclusion/Significance

These results provide strong evidence that semiannual MDA with albendazole alone is a safe and effective strategy for LF elimination in Central Africa. Community MDA also had a major impact on STH infections.

Prediction pipeline for discovery of regulatory motifs associated with <i>Brugia malayi</i> molting

PLoS Neglected Tropical Diseases News - 23 June 2020 - 9:00pm

by Alexandra Grote, Yichao Li, Canhui Liu, Denis Voronin, Adam Geber, Sara Lustigman, Thomas R. Unnasch, Lonnie Welch, Elodie Ghedin

Filarial nematodes can cause debilitating diseases in humans. They have complicated life cycles involving an insect vector and mammalian hosts, and they go through a number of developmental molts. While whole genome sequences of parasitic worms are now available, very little is known about transcription factor (TF) binding sites and their cognate transcription factors that play a role in regulating development. To address this gap, we developed a novel motif prediction pipeline, Emotif Alpha, that integrates ten different motif discovery algorithms, multiple statistical tests, and a comparative analysis of conserved elements between the filarial worms Brugia malayi and Onchocerca volvulus, and the free-living nematode Caenorhabditis elegans. We identified stage-specific TF binding motifs in B. malayi, with a particular focus on those potentially involved in the L3-L4 molt, a stage important for the establishment of infection in the mammalian host. Using an in vitro molting system, we tested and validated three of these motifs demonstrating the accuracy of the motif prediction pipeline.

COVID-19 in jails and prisons: A neglected infection in a marginalized population

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

by Carlos Franco-Paredes, Katherine Jankousky, Jonathan Schultz, Jessica Bernfeld, Kimberly Cullen, Nicolas G. Quan, Shelley Kon, Peter Hotez, Andrés F. Henao-Martínez, Martin Krsak

Access to Chagas disease treatment in the United States after the regulatory approval of benznidazole

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

by Kota Yoshioka, Jennifer Manne-Goehler, James H. Maguire, Michael R. Reich

Approximately 300,000 persons in the United States (US) are infected with Trypanosoma cruzi, the protozoan that causes Chagas disease, but less than 1% are estimated to have received antiparasitic treatment. Benznidazole was approved by the US Food and Drug Administration (FDA) for treatment of T. cruzi infection in 2017 and commercialized in May 2018. This paper analyzes factors that affect access to benznidazole following commercialization and suggests directions for future actions to expand access. We applied an access framework to identify barriers, facilitators, and key actors that influence the ability of people with Chagas disease to receive appropriate treatment with benznidazole. Data were collected from the published literature, key informants, and commercial databases. We found that the mean number of persons who obtained benznidazole increased from just under 5 when distributed by the CDC to 13 per month after the commercial launch (from May 2018 to February 2019). Nine key barriers to access were identified: lack of multi-sector coordination, failure of health care providers to use a specific order form, lack of an emergency delivery system, high medical costs for uninsured patients, narrow indications for use of benznidazole, lack of treatment guidelines, limited number of qualified treaters, difficulties for patients to make medical appointments, and inadequate evaluation by providers to determine eligibility for treatment. Our analysis shows that access to benznidazole is still limited after FDA approval. We suggest six areas for strategic action for the pharmaceutical company that markets benznidazole and its allied private foundation to expand access to benznidazole in the US. In addition, we recommend expanding the existing researcher-clinician network by including government agencies, companies and others. This paper’s approach could be applied to access programs for benznidazole in other countries or for other health products that target neglected populations throughout the world.

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