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High-throughput multiplex qPCRs for the surveillance of zoonotic species of canine hookworms

PLoS Neglected Tropical Diseases News - 15 June 2020 - 9:00pm

by Luca Massetti, Vito Colella, Patsy A. Zendejas, Dinh Ng-Nguyen, Lana Harriott, Lara Marwedel, Anke Wiethoelter, Rebecca J. Traub

The canine hookworms Ancylostoma braziliense, Ancylostoma ceylanicum, Ancylostoma caninum and Uncinaria stenocephala are not only capable of producing morbidity and mortality in dogs but are also neglected tropical zoonoses. Each hookworm species differs considerably in its geographical distribution, life cycle, biology, pathogenic impacts on both canine and human hosts, zoonotic potential and response to treatment with anthelminthics. Here we describe the development and validation of two Taq-Man based multiplex PCR assays capable of detecting and differentiating all four canine hookworm species in faeces of naturally infected dogs. The analytical sensitivity of both assays was assessed using 10-fold serial dilutions of synthetic gene block fragments containing individual sequence targets of each hookworm species. The sensitivity of the assays and ability to detect mixed species infections were compared to a conventional PCR-Restriction Fragment Length Polymorphism based-approach when applied to laboratory and field samples from endemic areas. The qPCRs detected at least one species of hookworms in 82.4% of PCR-RFLP-negative but microscopy-positive samples. The qPCRs detected an additional 68% mixed infections with different species of canine hookworms, and additional single species infection with A. caninum (47%), U. stenocephala (33%) and A. ceylanicum (0.02%) that were missed by PCR-RFLP. These multiplex qPCR assays will assist field based epidemiological surveillance studies towards an accurate and sensitive monitoring of canine hookworm infections in dogs, to inform their species-specific zoonotic risks to populations living in endemic areas, globally.

Early immune response against <i>Fonsecaea pedrosoi</i> requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis

PLoS Neglected Tropical Diseases News - 15 June 2020 - 9:00pm

by Isaque Medeiros Siqueira, Marcel Wüthrich, Mengyi Li, Huafeng Wang, Lucas de Oliveira La-Casas, Raffael Júnio Araújo de Castro, Bruce Klein, Anamelia Lorenzetti Bocca

Chromoblastomycosis (CBM) is a chronic worldwide subcutaneous mycosis, caused by several dimorphic, pigmented dematiaceous fungi. It is difficult to treat patients with the disease, mainly because of its recalcitrant nature. The correct activation of host immune response is critical to avoid fungal persistence in the tissue and disease chronification. CD4+ T cells are crucial for the development of protective immunity to F. pedrosoi infection. Here, we investigated T helper cell response dynamics during experimental CBM. Following footpad injection with F. pedrosoi hyphae and conidia, T cells were skewed towards a Th17 and Th1 phenotype. The Th17 population was the main Th cell subset found in the infected area during the early stages of experimental murine CBM, followed by Th1 predominance in the later stages, coinciding with the remission phase of the disease in this experimental model. Depletion of CD25+ cells, which leads to a reduction of Treg cells in the draining lymph node, resulted in decline in fungal burden after 14 days of infection. However, fungal cells were not cleared in the later stages of the disease, prolonging CBM clinical features in those animals. IL-17A and IFN-γ neutralization hindered fungal cell elimination in the course of the disease. Similarly, in dectin-2 KO animals, Th17 contraction in the course of experimental CBM was accompanied by fungal burden decrease in the first 14 days of infection, although it did not affect disease resolution. In this study, we gained insight into T helper subsets’ dynamics following footpad injections of F. pedrosoi propagules and uncovered their contribution to disease resolution. The Th17 population proved to be important in eliminating fungal cells in the early stages of infection. The Th1 population, in turn, closely assisted by Treg cells, proved to be relevant not only in the elimination of fungal cells at the beginning of infection but also essential for their complete elimination in later stages of the disease in a mouse experimental model of CBM.

A Systematic Review and Meta-Analysis to assess the association between Urogenital Schistosomiasis and HIV/AIDS Infection

PLoS Neglected Tropical Diseases News - 15 June 2020 - 9:00pm

by Ludoviko Zirimenya, Fatima Mahmud-Ajeigbe, Ruth McQuillan, You Li

Background

Urogenital schistosomiasis and HIV/AIDS infections are widespread in sub-Saharan Africa (SSA) leading to substantial morbidity and mortality. The co-occurrence of both diseases has led to the possible hypothesis that urogenital schistosomiasis leads to increased risk of acquiring HIV infection. However, the available evidence concerning this association is inconsistent. The aim of this study was to systematically review and quantitatively synthesize studies that investigated the association between urogenital schistosomiasis and HIV/AIDS infection.

Methods

A systematic review basing on PRISMA guidelines was conducted. It is registered with PROSPERO, number CRD42018116648. We searched four databases, MEDLINE, EMBASE, Global Health and Global Index Medicus for studies investigating the association between urogenital schistosomiasis and HIV infection. Only studies published in English were considered. Results of the association were summarised by gender. A meta-analysis was performed for studies on females using random-effects model and a pooled OR with 95% confidence interval was reported.

Results

Of the 993 studies screened, only eight observational studies met the inclusion criteria. Across all studies, the reported unadjusted OR ranged from 0.78 to 3.76. The pooled estimate of unadjusted OR among females was 1.31 (95% CI: 0.87–1.99). Only four of the eight studies reported an adjusted OR. A separate meta-analysis done in the three studies among females that reported an adjusted OR showed that the pooled estimate was 1.85 (95% CI: 1.17–2.92). There were insufficient data to pool results for association between urogenital schistosomiasis and HIV infection in the males.

Conclusion

Our investigation supports the hypothesis of an association between urogenital schistosomiasis with HIV/AIDS infection in females. Due to insufficient evidence, no conclusion could be drawn in males with urogenital schistosomiasis. Large-scale prospective studies are needed in future.

Development of a small animal model for deer tick virus pathogenesis mimicking human clinical outcome

PLoS Neglected Tropical Diseases News - 15 June 2020 - 9:00pm

by Meghan E. Hermance, Charles E. Hart, Allen T. Esterly, Erin S. Reynolds, Jahnavi R. Bhaskar, Saravanan Thangamani

Powassan virus (POWV) is a tick-borne flavivirus that encompasses two genetic lineages, POWV (Lineage I) and deer tick virus (DTV, Lineage II). In recent years, the incidence of reported POWV disease cases has increased, coupled with an expanded geographic range of the DTV tick vector, Ixodes scapularis. POWV and DTV are serologically indistinguishable, and it is not known whether clinical manifestations, pathology, or disease outcome differ between the two viruses. Six-week-old male and female BALB/c mice were footpad-inoculated with DTV doses ranging from 101 to 105 FFU. Dose-independent mortality, morbidity, and organ viral loads were observed for mice inoculated with sequentially increasing doses of DTV. By study completion, all surviving mice had cleared their viremias but detectable levels of negative-sense DTV RNA were present in the brain, indicating viral persistence of infectious DTV in the central nervous system. For mice that succumbed to disease, neuropathology revealed meningoencephalitis characterized by microscopic lesions with widespread distribution of viral RNA in the brain. These findings, coupled with the rapid onset of neurological signs of disease and high viral titers in nervous tissue, highlight the neurotropism of DTV in this mouse model. Additionally, disease outcome for DTV-infected mice was not affected by sex, as males and females were equally susceptible to disease. This is the first study to comprehensively characterize the clinical disease outcome in a small animal model across a spectrum of POWV/DTV infection doses. Here, we developed a small animal model for DTV pathogenesis that mimics the manifestations of POWV disease in humans. Since it is currently not known whether DTV and POWV differ in their capacity to cause human disease, the animal model detailed in our study could be utilized in future comparative pathogenesis studies, or as a platform for testing the efficacy of vaccines, and anti-virals.

Ongoing transmission of <i>Entamoeba histolytica</i> among newly diagnosed people living with HIV in Taiwan, 2009-2018

PLoS Neglected Tropical Diseases News - 12 June 2020 - 9:00pm

by Sung-Hsi Huang, Mao-Song Tsai, Chun-Yuan Lee, Chin-Shiang Tsai, Chun-Eng Liu, Yuan-Ti Lee, Hong-An Chen, Ling-Ya Chen, Yu-Man Lu, Wan-Chen Tsai, Wei-Ting Hsu, Wang-Da Liu, Chia-Jui Yang, Hsin-Yun Sun, Wen-Chien Ko, Po-Liang Lu, Chien-Ching Hung, Taiwan HIV Study Group

Recent outbreaks of enterically transmitted infections, including acute hepatitis A and shigellosis, have raised the concerns of increasing Entamoeba histolytica infection (EHI) among people living with HIV (PLWH) in Taiwan. This study investigated the prevalence of EHI, its temporal trends, and associated factors among newly diagnosed PLWH in Taiwan. Medical records of newly diagnosed PLWH at six medical centers in Taiwan between 2009 and 2018 were reviewed. The annual prevalence of invasive amoebiasis and seroprevalence of E. histolytica were determined and examined by the Cochran-Armitage test. The clinical characteristics associated with invasive amoebiasis and seropositivity for E. histolytica were analyzed in multivariable regression models. Among 5362 patients seeking HIV care at six medical centers in Taiwan during the 10-year study period, 119 (2.2%) had invasive amoebiasis at the time or within six months of their HIV diagnosis. Among 3499 who had indirect hemagglutination antibody (IHA) determined, 284 (8.1%) had positive IHA (≥1:32) and 205 (5.9%) had high-titre IHA (≥1:128). The prevalence of invasive amoebiasis increased from 1.3% in 2012 to 3.3% in 2018 (p = 0.024). Invasive amoebiasis was independently associated with a greater age, men who have sex with men, rapid plasma reagin titre ≥1:4, and concurrent shigellosis and giardiasis. Increasing prevalence of invasive amoebiasis among newly diagnosed PLWH in Taiwan calls for strategies to prevent ongoing transmission in this population. Routine screening of EHI for early diagnosis and treatment is recommended, especially among men who have sex with men and those who present with other sexually or enterically transmitted infections.

Environmental influences on <i>Aedes aegypti</i> catches in Biogents Sentinel traps during a Californian “rear and release” program: Implications for designing surveillance programs

PLoS Neglected Tropical Diseases News - 12 June 2020 - 9:00pm

by Kyran M. Staunton, Jacob E. Crawford, Devon Cornel, Peter Yeeles, Mark Desnoyer, Josh Livni, Jodi Holeman, F. Stephen Mulligan, Nigel Snoad, Scott A. Ritchie

As Aedes aegypti continues to expand its global distribution, the diseases it vectors (dengue, Zika, chikungunya and yellow fever) are of increasing concern. Modern efforts to control this species include “rear and release” strategies where lab-reared mosquitoes are distributed throughout the landscape to replace or suppress invasive populations. These programs require intensive surveillance efforts to monitor their success, and the Biogents Sentinel (BGS) trap is one of the most effective tools for sampling adult Ae. aegypti. BGS trap catches can be highly variable throughout landscapes, so we investigated the potential impacts of environmental factors on adult Ae. aegypti capture rates during a “rear and release” program in California to better understand the relative contributions of true variability in population density across a landscape and trap context. We recorded male and female Ae. aegypti catches from BGS traps, with and without CO2, throughout control sites where no mosquitoes were released and in treatment sites where males infected with Wolbachia were released. BGS trap catches were positively influenced by higher proportions of shade or bushes in the front yard of the premises as well as the presence of potential larval habitats such as subterranean vaults. In contrast, an increase in residential habitat within a 100 m radius of trap locations negatively influenced BGS trap catches. For male Ae. aegypti, increased visual complexity of the trap location positively influenced capture rates, and the presence of yard drains negatively affected catch rates in control sites. Lastly, for BGS traps using CO2, higher catch rates were noted from traps placed greater than one meter from walls or fences for both male and female mosquitoes. These results have important implications for surveillance programs of Ae. aegypti throughout the Californian urban environment including adult monitoring during “rear and release” programs.

<i>Ex vivo</i> susceptibilities of <i>Plasmodium vivax</i> isolates from the China-Myanmar border to antimalarial drugs and association with polymorphisms in <i>Pvmdr1</i> and <i>Pvcrt-o</i> genes

PLoS Neglected Tropical Diseases News - 12 June 2020 - 9:00pm

by Jiangyan Li, Jie Zhang, Qian Li, Yue Hu, Yonghua Ruan, Zhiyong Tao, Hui Xia, Jichen Qiao, Lingwen Meng, Weilin Zeng, Cuiying Li, Xi He, Luyi Zhao, Faiza A. Siddiqui, Jun Miao, Zhaoqing Yang, Qiang Fang, Liwang Cui

Background

Vivax malaria is an important public health problem in the Greater Mekong Subregion (GMS), including the China-Myanmar border. Previous studies have found that Plasmodium vivax has decreased sensitivity to antimalarial drugs in some area of GMS, but the sensitivity of P. vivax to antimalarial drugs is unclear in the China-Myanmar border. Here, we investigate the drug sensitivity profile and genetic variations for two drug resistance related genes, in P. vivax isolates to provide baseline information for future drug studies in the China-Myanmar border.

Methodology/Principal findings

A total of 64 P. vivax clinical isolates collected from the China-Myanmar border area were assessed for ex vivo susceptibility to eight antimalarial drugs by the schizont maturation assay. The medians of IC50 (half-maximum inhibitory concentrations) for chloroquine, mefloquine, pyronaridine, piperaquine, quinine, artesunate, artemether, dihydroartemisinin were 84.2 nM, 34.9 nM, 4.0 nM, 22.3 nM, 41.4 nM, 2.8 nM, 2.1 nM and 2.0 nM, respectively. Twelve P. vivax clinical isolates were found over the cut-off IC50 value (220 nM) for chloroquine resistance. In addition, sequence polymorphisms in pvmdr1 (P. vivax multidrug resistance-1), pvcrt-o (P. vivax chloroquine resistance transporter-o), and difference in pvmdr1 copy number were studied. Sequencing of the pvmdr1 gene in 52 samples identified 12 amino acid substitutions, among which two (G698S and T958M) were fixed, M908L were present in 98.1% of the isolates, while Y976F and F1076L were present in 3.8% and 78.8% of the isolates. Amplification of the pvmdr1 gene was only detected in 4.8% of the samples. Sequencing of the pvcrt-o in 59 parasite isolates identified a single lysine insertion at position 10 in 32.2% of the isolates. The pvmdr1 M908L substitutions in pvmdr1 in our samples was associated with reduced sensitivity to and chloroquine, mefloquine, pyronaridine, piperaquine, quinine, artesunate and dihydroartemisinin.

Conclusions

Our findings depict a drug sensitivity profile and genetic variations of the P. vivax isolates from the China-Myanmar border area, and suggest possible emergence of chloroquine resistant P. vivax isolates in the region, which demands further efforts for resistance monitoring and mechanism studies.

Use of pyriproxyfen in control of <i>Aedes</i> mosquitoes: A systematic review

PLoS Neglected Tropical Diseases News - 12 June 2020 - 9:00pm

by John Christian Hustedt, Ross Boyce, John Bradley, Jeffrey Hii, Neal Alexander

Background

Dengue is the most rapidly spreading arboviral disease in the world. The current lack of fully protective vaccines and clinical therapeutics creates an urgent need to identify more effective means of controlling Aedes mosquitos, principally Aedes aegypti, as the main vector of dengue. Pyriproxyfen (PPF) is an increasingly used hormone analogue that prevents juvenile Aedes mosquitoes from becoming adults and being incapable of transmitting dengue. The objectives of the review were to (1) Determine the effect of PPF on endpoints including percentage inhibition of emergence to adulthood, larval mortality, and resistance ratios; and (2) Determine the different uses, strengths, and limitations of PPF in control of Aedes. A systematic search was applied to Pubmed, EMBASE, Web of Science, LILACS, Global Health, and the Cochrane database of Systematic Reviews. Out of 1,369 records, 90 studies met the inclusion criteria. Nearly all fit in one of the following four categories 1) Efficacy of granules, 2) Auto-dissemination/horizontal transfer, 3) use of ultra-low volume thermal fogging (ULV), thermal fogging (TF), or fumigant technologies, and 4) assessing mosquito resistance. PPF granules had consistently efficacious results of 90–100% inhibition of emergence for up to 90 days. The evidence is less robust but promising regarding PPF dust for auto-dissemination and the use of PPF in ULV, TF and fumigants. Several studies also found that while mosquito populations were still susceptible to PPF, the lethal concentrations increased among temephos-resistant mosquitoes compared to reference strains. The evidence is strong that PPF does increase immature mortality and adult inhibition in settings represented in the included studies, however future research should focus on areas where there is less evidence (e.g. auto-dissemination, sprays) and new use cases for PPF. A better understanding of the biological mechanisms of cross-resistance between PPF, temephos, and other insecticides will allow control programs to make better informed decisions.

A comparative analysis of the 2007 and 2017 Italian chikungunya outbreaks and implication for public health response

PLoS Neglected Tropical Diseases News - 11 June 2020 - 9:00pm

by Beniamino Caputo, Gianluca Russo, Mattia Manica, Francesco Vairo, Piero Poletti, Giorgio Guzzetta, Stefano Merler, Carolina Scagnolari, Angelo Solimini

Key results

Both outbreaks started in small towns, but cases were also detected in nearby larger cities where transmission was limited to small clusters. The time spans between the first and the last symptom onsets were similar between the 2 outbreaks, and the delay from the symptom onset of the index case and the first case notified was considerable. Comparable infection and transmission rates were observed in laboratory. The basic reproductive number (R0) was estimated in the range of 1.8–6 (2007) and 1.5–2.6 (2017). Clinical characteristics were similar between outbreaks, and no acute complications were reported, though a higher frequency of ocular symptoms, myalgia, and rash was observed in 2017. Very little is known about the immune mediator profile of CHIKV-infected patients during the 2 outbreaks. Regarding public health responses, after the 2007 outbreak, the Italian Ministry of Health developed national guidelines to implement surveillance and good practices to prevent and control autochthonous transmission. However, only a few regional authorities implemented it, and the perception of outbreak risk and knowledge of clinical symptoms and transmission dynamics by general practitioners remained low.

Major conclusions

Efforts should be devoted to developing suitable procedures for early detection of virus circulation in the population, possibly through the analysis of medical records in near real time. Increasing the awareness of CHIKV of general practitioners and public health officials through tailored education may be effective, especially in small coastal towns where the outbreak risk may be higher. A key element is also the shift of citizen awareness from considering Aedes mosquitoes not only as a nuisance problem but also as a public health one. We advocate the need of strengthening the surveillance and of promoting the active participation of the communities to prevent and contain future outbreaks.

Inclusion of women susceptible to and becoming pregnant in preregistration clinical trials in low- and middle-income countries: A proposal for neglected tropical diseases

PLoS Neglected Tropical Diseases News - 11 June 2020 - 9:00pm

by Monique Couderc-Pétry, Elisabeth Eléfant, Monique Wasunna, Alwyn Mwinga, Nilima A. Kshirsagar, Nathalie Strub-Wourgaft

Role of three tick species in the maintenance and transmission of Severe Fever with Thrombocytopenia Syndrome Virus

PLoS Neglected Tropical Diseases News - 10 June 2020 - 9:00pm

by Yuan-Yuan Hu, Lu Zhuang, Kun Liu, Yi Sun, Ke Dai, Xiao-Ai Zhang, Pan-He Zhang, Zhi-Chun Feng, Hao Li, Wei Liu

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus in the Bunyaviridae family, causing SFTS with high mortality rate. Haemaphysalis longicornis ticks has been demonstrated as a competent vector of SFTSV by experimental transmission study and field study. However, there has been query whether other tick species that infest human beings in the SFTS endemic regions are capable of transmitting the pathogen. Here by performing experimental transmission study, we compared the capable of transmitting SFTSV among Ixodes sinensis, Ixodes persulcatus and Dermacentor silvarum ticks. The transovarial transmission was seen in the I. sinensis ticks with a rate of 40%, but neither in I. persulcatus nor in D. silvarum ticks. I. sinensis ticks also have the ability to transmit SFTSV horizontally to uninfected mice at 7 days after feeding, but not for I. persalcatus or D. silvarum ticks. In the transstadial transmission of I. persulcatus and D. silvarum ticks, I. persulcatus ticks were tested negative from larvae to adults. But the D. silvarum ticks were tested positive from larvae to nymphs, with the positive rate of 100% (10/10) for engorged larval ticks and 81.25% (13/16) for molted nymphs. However, the mice bitten by SFTSV-infected D. silvarum nymphs were negative for SFTSV detection. Therefore, there is not enough evidence to prove the transstadial transmission of SFTSV in I. persalcatus and D. silvarum ticks.

Movement of St. Louis encephalitis virus in the Western United States, 2014- 2018

PLoS Neglected Tropical Diseases News - 10 June 2020 - 9:00pm

by Daniele M. Swetnam, Jackson B. Stuart, Katherine Young, Payal D. Maharaj, Ying Fang, Sandra Garcia, Christopher M. Barker, Kirk Smith, Marvin S. Godsey, Harry M. Savage, Vonnita Barton, Bethany G. Bolling, Nisha Duggal, Aaron C. Brault, Lark L. Coffey

St. Louis encephalitis virus (SLEV) is a flavivirus that circulates in an enzootic cycle between birds and mosquitoes and can also infect humans to cause febrile disease and sometimes encephalitis. Although SLEV is endemic to the United States, no activity was detected in California during the years 2004 through 2014, despite continuous surveillance in mosquitoes and sentinel chickens. In 2015, SLEV-positive mosquito pools were detected in Maricopa County, Arizona, concurrent with an outbreak of human SLEV disease. SLEV-positive mosquito pools were also detected in southeastern California and Nevada in summer 2015. From 2016 to 2018, SLEV was detected in mosquito pools throughout southern and central California, Oregon, Idaho, and Texas. To understand genetic relatedness and geographic dispersal of SLEV in the western United States since 2015, we sequenced four historical genomes (3 from California and 1 from Louisiana) and 26 contemporary SLEV genomes from mosquito pools from locations across the western US. Bayesian phylogeographic approaches were then applied to map the recent spread of SLEV. Three routes of SLEV dispersal in the western United States were identified: Arizona to southern California, Arizona to Central California, and Arizona to all locations east of the Sierra Nevada mountains. Given the topography of the Western United States, these routes may have been limited by mountain ranges that influence the movement of avian reservoirs and mosquito vectors, which probably represents the primary mechanism of SLEV dispersal. Our analysis detected repeated SLEV introductions from Arizona into southern California and limited evidence of year-to-year persistence of genomes of the same ancestry. By contrast, genetic tracing suggests that all SLEV activity since 2015 in central California is the result of a single persistent SLEV introduction. The identification of natural barriers that influence SLEV dispersal enhances our understanding of arbovirus ecology in the western United States and may also support regional public health agencies in implementing more targeted vector mitigation efforts to protect their communities more effectively.

Video as a public health knowledge transfer tool in Burkina Faso: A mixed evaluation comparing three narrative genres

PLoS Neglected Tropical Diseases News - 10 June 2020 - 9:00pm

by Catherine Hébert, Christian Dagenais, Esther Mc Sween-Cadieux, Valéry Ridde

Background

The dengue virus is endemic in many low- and middle-income countries. In Burkina Faso, the proportion of fevers that could be due to dengue is growing. In 2013, a dengue epidemic spread there, followed by other seasonal outbreaks. Dengue is often confused with malaria, and health workers are not trained to distinguish between them. Three training videos using different narrative genres were tested with nursing students from two institutions in Ouagadougou: journalistic, dramatic and animated video. The study aimed to determine if video is an effective knowledge transfer tool, if narrative genre plays a role in knowledge acquisition, and which narrative elements are the most appreciated.

Methodology

A mixed method research design was used. The relative effectiveness of the videos was verified through a quasi-experimental quantitative component with a comparison group and post-test measurements. A qualitative component identified participants’ perceptions regarding the three videos. Data were drawn from a knowledge test (n = 482), three focus groups with health professionals’ students (n = 46), and individual interviews with health professionals (n = 10). Descriptive statistics and single-factor variance analysis were produced. A thematic analysis was used to analyse qualitative data.

Principal findings

Results showed that all three videos led to significant rates of knowledge improvement when compared with the comparison group (p <0.05): 12.31% for the journalistic video, 20.58% for the dramatic video, and 18.91% for the animated video. The dramatic and animated videos produced a significantly higher increase in knowledge than did the journalistic video (with respectively 8.27% (p = 0.003) and 6.59% (p = 0.029) and can be considered equivalent with a difference of 1.68% (p = 0.895). Thematic analysis also revealed that these two videos were considered to be better knowledge transfer tools. Four key aspects are important to consider for a video to be effective: 1) transmitting information in a narrative form, 2) choosing good communicators, 3) creating a visual instrument that reinforces the message and 4) adapting the message to the local context.

Conclusions

Video has proven to be an effective and appreciated knowledge transfer and training tool for health professionals, but the narrative genre of the videos can influence knowledge acquisition. The production of other videos should be considered for training or updating health professionals and their narrative genre taken into consideration. The actual context of constant circulation of new diseases, such as COVID-19, reaffirms the need to train health professionals.

Enteric parasitic infections in children and dogs in resource-poor communities in northeastern Brazil: Identifying priority prevention and control areas

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

by Tatiani Vitor Harvey, Alice M. Tang, Anaiá da Paixao Sevá, Camila Albano dos Santos, Silvia Maria Santos Carvalho, Christiane Maria Barcellos Magalhães da Rocha, Bruno César Miranda Oliveira, George Rego Albuquerque

The aim of this study was to determine the prevalence and risk factors of the main enteric parasitic infections that affect children and dogs in the municipality of Ilhéus, Bahia, Brazil; and to identify the geopolitical areas that should receive priority interventions to combat them. Between March and November 2016, fecal samples of 143 dogs and 193 children aged 1 month to 5 years were collected in 40 rural and semirural communities using a systematic sampling approach, stratified by district. Samples were collected by legal guardians of the children and / or dog owners. Eggs, larvae, cysts and oocysts of parasites were concentrated by centrifugal-flotation and centrifugal-sedimentation, and acid-resistant staining was used to visualize parasites. One hundred and thirty-two children (68.4%), 111 dogs (77.6%) and 199 (73.7%) dog fecal samples collected from streets were parasitized. Giardiasis, cryptosporidiosis, amoeba infections and hookworm were the most frequent infections in all studied populations, in addition to trichuriasis in dogs and ascaridiasis in children. A predominance of Giardia and hookworms was observed in children and dogs, respectively. The coastal districts of Aritaguá, Olivença and the main district had a higher parasitic diversity and overlapping of important potential zoonotic infections. Age over one year (p<0.001), adjusted OR = 3.65; 95% CI = 1.86–7.16) and income below the minimum monthly salary (p = 0.02, adjusted OR = 2.78, 95% CI = 1.17–6.59) were the main factors associated with intestinal parasitic infections in children and dogs, respectively. The coastal districts of Aritaguá and Olivença and the main district should be prioritized through enteric disease control programs, and the factors associated with infections must be considered in the design of health interventions in these districts. The integration between affirmative income actions and investments to improve the health infrastructure of these communities may work more effectively than current preventive measures to combat enteric parasites.

Assessing the burden and spatial distribution of <i>Taenia solium</i> human neurocysticercosis in Ecuador (2013–2017)

PLoS Neglected Tropical Diseases News - 8 June 2020 - 9:00pm

by Marco Coral-Almeida, Aquiles R. Henriquez-Trujillo, Sofia Asanza, Celia Erazo, Michelle Paucar, Manuel Calvopiña

Background

Estimating the burden of neglected tropical diseases is a valuable tool to support policymakers in the resource allocation for control and elimination of these diseases. Spatial analysis allows to identify the geographical distribution patterns of infectious and parasitic diseases within a country and allows to assess their possible correlation with other health disorders. Despite being neurocysticercosis (NCC) considered as the most important parasitic disease of the nervous system, few efforts have been addressed to assess the real burden of NCC in endemic countries, to date, there are no studies estimating the burden of NCC in South America. In this study we aimed to use the Disability Adjust Life Years (DALY) and spatial indicators as tools to measure the impact of human neurocysticercosis in Ecuador between 2013 and 2017.

Methods

Mortality, morbidity and spatial data from the national agency of statistics were used to estimate the burden of disease of NCC during a five-year period (2013–2017). NCC cases and its two main sequelae, epilepsy and migraine headache, were stratified by sex and age group to calculate the DALY associated to NCC using the DALY package in R. SATSCAN software was used to assess spatial clusters of NCC and its possible neurological sequelae as epilepsy, status epilepticus, migraine and hydrocephalus.

Principal findings

The burden of human neurocysticercosis ranged from 56201 [95% CI 29961–89333] to 59612 [95% CI 31854–94689] DALY per year, corresponding to 3.54 to 3.56 DALY per 1000 population. Average yearly incidence rates per 10 000 person-years were 0.23 [95% CI 0.21–0.26] for NCC, 4.89 [95% CI 4.78–5.00] for epilepsy, 0.130 [95% CI 0.11–0.15] for status epilepticus, 0.62 [95% CI 0.58–0.66] for migraine headache, and 1.02 [95% CI 0.98–1.07] for hydrocephalus. Most important significant spatial clusters (p<0.0001) were located in the southern region of the highlands of the country.

Conclusion/Significance

This is the first study in South America to calculate estimates for burden of NCC and one of the few using spatial analysis to show the importance of sequelae other than epilepsy that play an important role in the impact of human neurocysticercosis.

Zika virus dysregulates human Sertoli cell proteins involved in spermatogenesis with little effect on tight junctions

PLoS Neglected Tropical Diseases News - 8 June 2020 - 9:00pm

by Mahamud-ur Rashid, Ali Zahedi-Amiri, Kathleen K. M. Glover, Ang Gao, Michaela E. Nickol, Jason Kindrachuk, John A. Wilkins, Kevin M. Coombs

Zika virus (ZIKV), a neglected tropical disease until its re-emergence in 2007, causes microcephaly in infants and Guillain-Barré syndrome in adults. Its re-emergence and spread to more than 80 countries led the World Health Organization in 2016 to declare a Public Health Emergency. ZIKV is mainly transmitted by mosquitos, but can persist in infected human male semen for prolonged periods and may be sexually transmitted. Testicular Sertoli cells support ZIKV replication and may be a reservoir for persistent ZIKV infection. Electrical impedance analyses indicated ZIKV infection rapidly disrupted Vero cell monolayers but had little effect upon human Sertoli cells (HSerC). We determined ZIKV-induced proteomic changes in HSerC using an aptamer-based multiplexed technique (SOMAscan) targeting >1300 human proteins. ZIKV infection caused differential expression of 299 proteins during three different time points, including 5 days after infection. Dysregulated proteins are involved in different bio-functions, including cell death and survival, cell cycle, maintenance of cellular function, cell signaling, cellular assembly, morphology, movement, molecular transport, and immune response. Many signaling pathways important for maintenance of HSerC function and spermatogenesis were highly dysregulated. These included IL-6, IGF1, EGF, NF-κB, PPAR, ERK/MAPK, and growth hormone signaling. Down-regulation of the PPAR signaling pathway might impact cellular energy supplies. Upstream molecule analysis also indicated microRNAs involved in germ cell development were downregulated by infection. Overall, this study leads to a better understanding of Sertoli cellular mechanisms used by ZIKV during persistent infection and possible ZIKV impacts on spermatogenesis.

The potential risk of <i>Schistosoma mansoni</i> transmission by the invasive freshwater snail <i>Biomphalaria straminea</i> in South China

PLoS Neglected Tropical Diseases News - 8 June 2020 - 9:00pm

by DaTao Lin, Xin Zeng, Benjamin Sanogo, Ping He, Suoyu Xiang, Shuling Du, YanHua Zhang, Lifu Wang, Shuo Wan, XingDa Zeng, Ya Yang, ZhiYue Lv, YouSheng Liang, ZhuoHui Deng, Jerome Ho-Lam Hui, DongJuan Yuan, Tao Ding, ZhongDao Wu, Xi Sun

Schistosomes infect more than 200 million people worldwide, and globally, over 700 million people are at risk of infection. The snail Biomphalaria straminea, as one of the intermediate hosts of Schistosoma mansoni, consecutively invaded Hong Kong in 1973, raising great concern in China. In this study, a malacological survey was conducted over a period of four years, and investigations were performed on the mechanism of susceptibility of B. straminea to S. mansoni. B. straminea was investigated in China from 2014 to 2018. Out of 185 investigated sites, 61 were positive for stages of black B. straminea (BBS), which shows pigmented spots. Twenty of the 61 sites were positive for red B. straminea (RBS), which is partially albino and red colored. Phylogenetic analyses based on cox1 and 16S rRNA sequences demonstrated that both phenotypes were clustered with Brazilian strains. No S. mansoni infections were detected in field-collected snail. However, in laboratory experiments, 4.17% of RBS were susceptible to a Puerto Rican strain of S. mansoni, while BBS was not susceptible. The highest susceptibility rate (70.83%) was observed in the F2 generation of RBS in lab. The density of RBS has increased from south to north and from west to east in Guangdong since 2014. Five tyrosinase tyrosine metabolism genes were upregulated in BBS. Transcriptome comparisons of RBS and BBS showed that ficolin, C1q, MASP-like, and membrane attack complex (MAC)/perforin models of the complement system were significantly upregulated in BBS. Our study demonstrated that B. straminea is widely distributed in Hong Kong and Guangdong Province, which is expanding northwards very rapidly as a consequence of its adaptation to local environments. Our results suggest that B. straminea from South China is susceptible to S. mansoni, implying the high potential for S. mansoni transmission and increased S. mansoni infection risk in China.

The relationship between clinics and the venom of the causative Amazon pit viper (<i>Bothrops atrox</i>)

PLoS Neglected Tropical Diseases News - 8 June 2020 - 9:00pm

by Ana Maria Moura-da-Silva, Jorge Carlos Contreras-Bernal, Sarah Natalie Cirilo Gimenes, Luciana Aparecida Freitas-de-Sousa, José Antonio Portes-Junior, Pedro da Silva Peixoto, Leo Kei Iwai, Valéria Mourão de Moura, Pedro Ferreira Bisneto, Marcus Lacerda, Iran Mendonça da Silva, Luiz Carlos de Lima Ferreira, Sâmella Silva de Oliveira, Fan Hui Wen, Jacqueline de Almeida Gonçalves Sachett, Wuelton M. Monteiro

Snake venoms are complex mixtures of proteins with toxic activities, with many distinct isoforms, affecting different physiological targets, comprised in a few protein families. It is currently accepted that this diversity in venom composition is an adaptive advantage for venom efficacy on a wide range of prey. However, on the other side, variability on isoforms expression has implications in the clinics of human victims of snakebites and in the efficacy of antivenoms. B. atrox snakes are responsible for most of the human accidents in Brazilian Amazon and the type and abundance of protein families on their venoms present individual variability. Thus, in this study we attempted to correlate the individual venom proteome of the snake brought to the hospital by the patient seeking for medical assistance with the clinical signs observed in the same patient. Individual variability was confirmed in venoms of the 14 snakes selected for the study. The abundance of each protein family was quite similar among the venom samples, while the isoforms composition was highly variable. Considering the protein families, the SVMP group presented the best correlation with bleeding disorders and edema. Considering individual isoforms, some isoforms of venom metalloproteinase (SVMP), C-type lectin-like toxins (CTL) and snake venom serine proteinases (SVSP) presented expression levels that with statistically significant positive correlation to signs and symptoms presented by the patients as bleeding disorders, edema, ecchymosis and blister formation. However, some unexpected data were also observed as the correlation between a CTL, CRISP or LAAO isoforms with blister formation, still to be confirmed with a larger number of samples. Although this is still a small number of patient samples, we were able to indicate that venom composition modulates clinical manifestations of snakebites, to confirm at the bedside the prominent role of SVMPs and to include new possible toxin candidates for the development of toxin inhibitors or to improve antivenom selectiveness, important actions for the next generation treatments of snakebites.

Safety and efficacy of co-administered diethylcarbamazine, albendazole and ivermectin during mass drug administration for lymphatic filariasis in Haiti: Results from a two-armed, open-label, cluster-randomized, community study

PLoS Neglected Tropical Diseases News - 8 June 2020 - 9:00pm

by Christine L. Dubray, Anita D. Sircar, Valery Madsen Beau de Rochars, Joshua Bogus, Abdel N. Direny, Jean Romuald Ernest, Carl R. Fayette, Charles W. Goss, Marisa Hast, Kobie O’Brian, Guy Emmanuel Pavilus, Daniel Frantz Sabin, Ryan E. Wiegand, Gary J. Weil, Jean Frantz Lemoine

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti.

SEN virus genotype H distribution in β-thalassemic patients and in healthy donors in Iraq: Molecular and physiological study

PLoS Neglected Tropical Diseases News - 8 June 2020 - 9:00pm

by Mushtak T. S. Al-Ouqaili, Yasin H. Majeed, Sahar K. Al-Ani

The SEN virus (SENV) has been linked to transfusion-associated non-A-E hepatitis; however, information regarding SENV infections in patients with thalassemia, particularly in those with hepatitis virus co-infections, remains limited. This study investigated the frequency of SENV (genotypes D and H) infections in Iraqi patients with thalassemic patients infected and not infected with hepatitis C virus. The study involved 150 β-thalassemia patients (75 with HCV infections and 75 without) and 75 healthy blood donors. Patient levels of vitamins C and E, liver function markers, and glutathione peroxidase (GPX) were determined. Recovered viral nucleic acids were amplified using the conventional polymerase chain reaction (SENV DNA) or the real-time polymerase chain reaction (HCV RNA) techniques. Only 10% of healthy donors had evidence of SENV infection. Among patients with thalassemia, 80% and 77% of patients with and without concurrent HCV infections, respectively, had SENV infections. DNA sequencing analyses were performed on blood samples obtained from 29 patients. Patients with thalassemia, particularly those with SENV infections, had higher levels of several enzymatic liver function markers and total serum bilirubin (P < 0.05) than did healthy blood donors. Among the examined liver function markers, only gamma-glutamyl transferase demonstrated significantly higher levels in HCV-negative patients infected with SENV-H than in those infected with SENV-D (P = 0.01). There were significantly lower vitamin C, vitamin E, and glutathione peroxidase levels in patients than in healthy donors (P < 0.05), but only glutathione peroxidase levels were significantly lower in HCV-negative thalassemia patients infected with SENV than in those without SENV infections (P = 0.04). The SENV-H genotype sequences were similar to the global standard genes in GenBank. These results broaden our understanding the nature of the SENV-H genotype and the differential role of SENV-H infections, compared to SENV-D infections, in patients with thalassemia, in Iraq.

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