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

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

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

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

Mycotic aneurysm secondary to melioidosis in China: A series of eight cases and a review of literature

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

by Hua Wu, Xuming Wang, Xiaojun Zhou, Zhicheng Wu, Yanyan Wang, Mengjie Pan, Binghuai Lu

Burkholderia pseudomallei is the causative agent of melioidosis, endemic in Southeast Asia and Northern Australia, and increasingly recognized in southern China, especially in Hainan Province. Mycotic aneurysm caused by B. pseudomallei is a rare but potentially severe illness with a high mortality rate. The clinical features of the mycotic aneurysm secondary to melioidosis have not been illustrated in China. Over a seven-year period (2013 to 2019), 159 patients with bacteremic melioidosis were retrospectively analyzed in Hainan province, China, of whom eight patients were confirmed to have mycotic aneurysm through the combination of imaging examination, pathologic examination and aneurysm tissue culture. We summarized these eight patients’ clinical characteristics, demographical features, treatments and outcomes. The susceptibilities to five commonly-used antibiotics for these eight B. pseudomallei isolates were also determined by E-test strips. Furthermore, the mycotic aneurysm cases secondary to melioidosis retrieved from the literature were also reviewed. Of the eight cases, six had abdominal mycotic aneurysms, one had a left iliac aneurysm, and the other one had an infectious mesenteric aneurysm. They were aged from 48 to 69 years old, and had the underlying risk factors of diabetes mellitus (2 patients), long-term smoking (4 patients), hypertension (6 patients), and soil and water contact history (6 patients), respectively. The positive arterial aneurysm imaging was observed in all patients via computed tomography (CT) or angiography. Eight B. pseudomallei isolates collected from both blood and mycotic aneurysm tissues remained 100% susceptible to imipenem and ceftazidime. After surgery combined with antibiotic administration, six patients survived, with a mortality rate of 25%. In melioidosis endemic areas, the mycotic aneurysm secondary to melioidosis might be underdiagnosed, and increased awareness of predisposing risk factors and clinical features of the mycotic aneurysm is required. Following a positive B. pseudomallei blood culture, the diagnosis of mycotic aneurysm should be under consideration in those with abdominal pain and/or hypertension. Imaging by CT or angiography is indispensable for its timely diagnosis and management.

The process of building the priority of neglected tropical diseases: A global policy analysis

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

by Nathaly Aya Pastrana, David Beran, Claire Somerville, Olivia Heller, Jorge C. Correia, L. Suzanne Suggs

The global burden attributed to Neglected Tropical Diseases (NTDs) is 47.9 million Disability-Adjusted Life Years (DALYs). These diseases predominantly affect disadvantaged populations. Priority for NTDs has grown in recent years, which is observed by their inclusion in the sustainable development goals (SDGs). This study analyzed the process that allowed these diseases to be included on the global health policy agenda. This global policy analysis used the Shiffman and Smith framework to understand the determinants of global health political priority for NTDs. The framework comprises four categories: actor power, ideas, political contexts, and issue characteristics. Global documents and World Health Assembly (WHA) resolutions were examined, key-informant interviews were conducted, and academic publications were reviewed to understand the four categories that comprise the framework. A total of 37 global policy documents, 15 WHA resolutions, and 38 academic publications were examined. Twelve semi-structured interviews were conducted with individuals representing different sectors within the NTD community who have been involved in raising the priority of these diseases. This study found that several factors helped better position NTDs in the global health agenda. These include the leadership of actors that mobilized the global health community, the creation of a label combining these diseases as a group to represent a larger disease burden, the presence of mechanisms aligning the NTD community, and the agreement on ways to present the NTD burden and potential solutions. The process of building the priority of NTDs in the global health agenda shows that several determinants led to positive outcomes, but these diseases continue to have low priority at the global level which requires the implementation of actions to increase their global priority. These include sustaining the commitment of current actors and engaging new ones; increasing the attention given to diseases formerly categorized as “tool-deficient”, including zoonotic NTDs; continue leveraging on policy windows and creating favorable policy moments to sustain commitment, as well as setting realistic targets. Findings from this study can help develop strategies to build the momentum and drive actions to implement the goals of the new Roadmap for NTDs in the pathway to universal health coverage (UHC) and sustainable development.

Yellow fever transmission in non-human primates, Bahia, Northeastern Brazil

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

by Jaqueline Goes de Jesus, Tiago Gräf, Marta Giovanetti, Maria Angélica Mares-Guia, Joilson Xavier, Maricelia Lima Maia, Vagner Fonseca, Allison Fabri, Roberto Fonseca dos Santos, Felicidade Mota Pereira, Leandro Ferraz Oliveira Santos, Luciana Reboredo de Oliveira da Silva, Zuinara Pereira Gusmão Maia, Jananci Xavier Gomes Cerqueira, Julien Thèze, Leandro Abade, Mirza de Carvalho Santana Cordeiro, Sintia Sacramento Cerqueira Torquato, Eloisa Bahia Santana, Neuza Santos de Jesus Silva, Rosemary Sarmento Oitiçica Dourado, Ademilson Brás Alves, Adeilde do Socorro Guedes, Pedro Macedo da Silva Filho, Nuno Rodrigues Faria, Carlos F. Campelo de Albuquerque, André Luiz de Abreu, Alessandro Pecego Martins Romano, Julio Croda, Rodrigo Fabiano do Carmo Said, Gabriel Muricy Cunha, Jeane Magnavita da Fonseca Cerqueira, Arabela Leal e Silva de Mello, Ana Maria Bispo de Filippis, Luiz Carlos Junior Alcantara

Yellow fever virus (YFV) causes a clinical syndrome of acute hemorrhagic hepatitis. YFV transmission involves non-human primates (NHP), mosquitoes and humans. By late 2016, Brazil experienced the largest YFV outbreak of the last 100 years, with 2050 human confirmed cases, with 681 cases ending in death and 764 confirmed epizootic cases in NHP. Among affected areas, Bahia state in Northeastern was the only region with no autochthonous human cases. By using next generation sequence approach, we investigated the molecular epidemiology of YFV in NHP in Bahia and discuss what factors might have prevented human cases. We investigated 47 YFV positive tissue samples from NHP cases to generate 8 novel YFV genomes. ML phylogenetic tree reconstructions and automated subtyping tools placed the newly generated genomes within the South American genotype I (SA I). Our analysis revealed that the YFV genomes from Bahia formed two distinct well-supported phylogenetic clusters that emerged most likely of an introduction from Minas Gerais and Espírito Santo states. Vegetation coverage analysis performed shows predominantly low to medium vegetation coverage in Bahia state. Together, our findings support the hypothesis of two independent YFV SA-I introductions. We also highlighted the effectiveness of the actions taken by epidemiological surveillance team of the state to prevented human cases.

COVID-19 and acute juvenile paracoccidioidomycosis coinfection

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

by Priscila Marques de Macedo, Dayvison Francis Saraiva Freitas, Andrea Gina Varon, Cristiane da Cruz Lamas, Livia Cristina Fonseca Ferreira, Andrea d’Avila Freitas, Marcel Treptow Ferreira, Estevão Portela Nunes, Marilda Mendonça Siqueira, Valdiléa G. Veloso, Antonio Carlos Francesconi do Valle

High endemicity of <i>Clonorchis sinensis</i> infection in Binyang County, southern China

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

by Junling Sun, Hualei Xin, Zhihua Jiang, Menbao Qian, Kaixia Duan, Yingdan Chen, Shizhu Li, Wei Li, Shiyong Huang, Xiaoqin Gan, Yichao Yang, Zhongjie Li

High-intensity clonorchiasis infection is associated with serious outcomes, including cancer. Understanding the infection intensity of Clonorchis sinensis and its risk factors in local endemic regions could facilitate effective control measures. In a county located in a highly endemic area in Guangxi Province, P. R. China, local residents were randomly enrolled in the study; helminth egg examinations were performed with the Kato-Katz method, and the intensity of infection was identified as mild, moderate or heavy. Knowledge, attitudes, and high-risk behaviours were investigated among those infected with Clonorchis sinensis. A total of 2521 local residents participated in this study, and the Clonorchis sinensis-positive proportion was 28.9% (728 persons). Among the infected persons, the percentages of mild, moderate and heavy infections were 66.2%, 28.4% and 5.4%, respectively. Males experienced a higher proportion of moderate and heavy infections (37.5%) than females (18.1%) (p<0.05). The highest infection proportion among the different levels of infection intensity was identified among persons aged 30–59 years (15.7% for moderate and heavy infections). Among the 509 persons who reported eating raw fish, 302 persons (59.3%) had eaten raw fresh fish for more than 10 years, and 131 (25.7%) persons ate raw fish ≥12 times a year. Multivariate logistic regression revealed that eating raw fish 12–50 times in the last year (adjusted odds ratio [aOR] = 1.74, 95%CI: 1.09–2.80) and eating raw fish >50 times in the last year (aOR = 2.89, 95%CI: 1.20–7.50) were risk factors for high-intensity infections (moderate and heavy). The overall infection proportion was high in the study area, with a large group of residents experiencing high-intensity infections. High frequency of raw fish consumption was associated with high-intensity infections. Intervention strategies targeting people with a high frequency of raw fish consumption should be implemented to reduce the probability of severe consequences.

Genomic epidemiology of <i>Campylobacter jejuni</i> associated with asymptomatic pediatric infection in the Peruvian Amazon

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

by Ben Pascoe, Francesca Schiaffino, Susan Murray, Guillaume Méric, Sion C. Bayliss, Matthew D. Hitchings, Evangelos Mourkas, Jessica K. Calland, Rosa Burga, Pablo Peñataro Yori, Keith A. Jolley, Kerry K. Cooper, Craig T. Parker, Maribel Paredes Olortegui, Margaret N. Kosek, Samuel K. Sheppard

Campylobacter is the leading bacterial cause of gastroenteritis worldwide and its incidence is especially high in low- and middle-income countries (LMIC). Disease epidemiology in LMICs is different compared to high income countries like the USA or in Europe. Children in LMICs commonly have repeated and chronic infections even in the absence of symptoms, which can lead to deficits in early childhood development. In this study, we sequenced and characterized C. jejuni (n = 62) from a longitudinal cohort study of children under the age of 5 with and without diarrheal symptoms, and contextualized them within a global C. jejuni genome collection. Epidemiological differences in disease presentation were reflected in the genomes, specifically by the absence of some of the most common global disease-causing lineages. As in many other countries, poultry-associated strains were likely a major source of human infection but almost half of local disease cases (15 of 31) were attributable to genotypes that are rare outside of Peru. Asymptomatic infection was not limited to a single (or few) human adapted lineages but resulted from phylogenetically divergent strains suggesting an important role for host factors in the cryptic epidemiology of campylobacteriosis in LMICs.

Incidence and etiology of clinically-attended, antibiotic-treated diarrhea among children under five years of age in low- and middle-income countries: Evidence from the Global Enteric Multicenter Study

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

by Joseph A. Lewnard, Elizabeth T. Rogawski McQuade, James A. Platts-Mills, Karen L. Kotloff, Ramanan Laxminarayan

Diarrhea is a leading cause of antibiotic consumption among children in low- and middle-income countries. While vaccines may prevent diarrhea infections for which children often receive antibiotics, the contribution of individual enteropathogens to antibiotic use is minimally understood. We used data from the Global Enteric Multicenter Study (GEMS) to estimate pathogen-specific incidence of antibiotic-treated diarrhea among children under five years old residing in six countries of sub-Saharan Africa and South Asia before rotavirus vaccine implementation. GEMS was an age-stratified, individually-matched case-control study. Stool specimens were obtained from children presenting to sentinel health clinics with newly-onset, acute diarrhea (including moderate-to-severe and less-severe diarrhea) as well as matched community controls without diarrhea. We used data from conventional and quantitative molecular diagnostic assays applied to stool specimens to estimate the proportion of antibiotic-treated diarrhea cases attributable to each pathogen. Antibiotics were administered or prescribed to 9,606 of 12,109 moderate-to-severe cases and 1,844 of 3,174 less-severe cases. Across all sites, incidence rates of clinically-attended, antibiotic-treated diarrhea were 12.2 (95% confidence interval: 9.0–17.8), 10.2 (7.4–13.9) and 1.9 (1.3–3.0) episodes per 100 child-years at risk at ages 6 weeks to 11 months, 12–23 months, and 24–59 months, respectively. Based on the recommendation for antibiotic treatment to be reserved for cases with dysentery, we estimated a ratio of 12.6 (8.6–20.8) inappropriately-treated diarrhea cases for each appropriately-treated case. Rotavirus, adenovirus serotypes 40/41, Shigella, sapovirus, Shiga toxin-producing Escherichia coli, and Cryptosporidium were the leading antibiotic-treated diarrhea etiologies. Rotavirus caused 29.2% (24.5–35.2%) of antibiotic-treated cases, including the largest share in both the first and second years of life. Shigella caused 14.9% (11.4–18.9%) of antibiotic-treated cases, and was the leading etiology at ages 24–59 months. Our findings should inform the prioritization of vaccines with the greatest potential to reduce antibiotic exposure among children.

Epidemiological distribution of <i>Echinococcus granulosus s</i>.<i>l</i>. infection in human and domestic animal hosts in European Mediterranean and Balkan countries: A systematic review

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

by Francesca Tamarozzi, Matteo Legnardi, Andrea Fittipaldo, Michele Drigo, Rudi Cassini

Cystic echinococcosis (CE) is a neglected zoonosis caused by infection with the cestode Echinococcus granulosus sensu lato. We carried out a systematic literature review on E. granulosus s.l. human and animal (cattle, sheep, dog) infection in European Mediterranean and Balkan countries in 2000–2019, to provide a picture of its recent epidemiology in this endemic area. MEDLINE, EMBASE, Scopus, Google Scholar and Open Grey databases were searched. Included cases were: i) for humans, data from hospital records and imaging studies; ii) for dogs, data from necropsy and coprological studies; iii) for ruminants, cases based on slaughter inspection. The NUTS (Nomenclature of Territorial Units for Statistics) classification was used to categorize extracted data in epidemiological units, defined as data referred to one NUTS2 (basic region) in one year time. Data were then aggregated to NUTS1 level (major regions), calculating the average incidence value of included epidemiological units. For prevalence studies covering different epidemiological units, the pooled prevalence was estimated. Data were extracted from 79 publications, 25 on human infection (covering 437 epidemiological units), and 54 on animal infection (52 epidemiological units for cattle, 35 for sheep and 25 for dogs). At NUTS1 level, average annual incidence rates of human CE ranged from 0.10–7.74/100,000; pooled prevalence values ranged from 0.003–64.09% in cattle, 0.004–68.73% in sheep, and 0–31.86% in dogs. Southern and insular Italy, central Spain, Romania and Bulgaria reported the highest values. Bovine data showed a more similar pattern to human data compared to sheep and dogs. Limitation of evidence included the paucity of human prevalence studies, data heterogeneity, and the patchy geographical coverage, with lack of data especially for the Balkans. Our results confirm Italy, Spain, and Eastern Europe being the most affected areas, but data are extremely heterogeneous, geographical coverage very patchy, and human prevalence studies extremely scant. Results also highlight the notorious problem of underreporting of E. granulosus s.l. infection in both humans and animals.

The global progress of soil-transmitted helminthiases control in 2020 and World Health Organization targets for 2030

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

by Antonio Montresor, Denise Mupfasoni, Alexei Mikhailov, Pauline Mwinzi, Ana Lucianez, Mohamed Jamsheed, Elkan Gasimov, Supriya Warusavithana, Aya Yajima, Zeno Bisoffi, Dora Buonfrate, Peter Steinmann, Jürg Utzinger, Bruno Levecke, Johnny Vlaminck, Piet Cools, Jozef Vercruysse, Giuseppe Cringoli, Laura Rinaldi, Brittany Blouin, Theresa W. Gyorkos

Soil-transmitted helminth (STH) infections are the most widespread of the neglected tropical diseases, primarily affecting marginalized populations in low- and middle-income countries. More than one billion people are currently infected with STHs. For the control of these infections, the World Health Organization (WHO) recommends an integrated approach, which includes access to appropriate sanitation, hygiene education, and preventive chemotherapy (i.e., large-scale, periodic distribution of anthelmintic drugs). Since 2010, WHO has coordinated two large donations of benzimidazoles to endemic countries. Thus far, more than 3.3 billion benzimidazole tablets have been distributed in schools for the control of STH infections, resulting in an important reduction in STH-attributable morbidity in children, while additional tablets have been distributed for the control of lymphatic filariasis. This paper (i) summarizes the progress of global STH control between 2008 to 2018 (based on over 690 reports submitted by endemic countries to WHO); (ii) provides regional and country details on preventive chemotherapy coverage; and (iii) indicates the targets identified by WHO for the next decade and the tools that should be developed to attain these targets. The main message is that STH-attributable morbidity can be averted with evidence-informed program planning, implementation, and monitoring. Caution will still need to be exercised in stopping control programs to avoid any rebound of prevalence and loss of accrued morbidity gains. Over the next decade, with increased country leadership and multi-sector engagement, the goal of eliminating STH infections as a public health problem can be achieved.

Efficacy of histamine H1 receptor antagonists azelastine and fexofenadine against cutaneous <i>Leishmania major</i> infection

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

by Alex G. Peniche, E. Yaneth Osorio, Peter C. Melby, Bruno L. Travi

Current drug therapies for cutaneous leishmaniasis are often difficult to administer and treatment failure is an increasingly common occurrence. The efficacy of antileishmanial therapy relies on a combination of anti-parasite activity of drugs and the patient’s immune response. Previous studies have reported in vitro antimicrobial activity of histamine 1-receptor antagonists (H1RAs) against different pathogens. We used an ex vivo explant culture of lymph nodes from mice infected with Leishmania major to screen H1RAs compounds. Azelastine (AZ) and Fexofenadine (FX) showed remarkable ex vivo efficacy (EC50 = 0.05 and 1.50 μM respectively) and low in vitro cytotoxicity yielding a high therapeutic index. AZ significantly decreased the expression of H1R and the proinflammatory cytokine IL-1ẞ in the ex vivo system, which were shown to be augmented by histamine addition. The anti-leishmanial efficacy of AZ was enhanced in the presence of T cells from infected mice suggesting an immune-modulatory mechanism of parasite suppression. L. major infected BALB/c mice treated per os with FX or intralesionally with AZ showed a significant reduction of lesion size (FX = 69%; AZ = 52%). Furthermore, there was significant parasite suppression in the lesion (FX = 82%; AZ = 87%) and lymph nodes (FX = 81%; AZ = 36%) with no observable side effects. AZ and FX and potentially other H1RAs are good candidates for assessing efficacy in larger studies as monotherapies or in combination with current anti-leishmanial drugs to treat cutaneous leishmaniasis.

Modelling geospatial distributions of the triatomine vectors of <i>Trypanosoma cruzi</i> in Latin America

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

by Andreas Bender, Andre Python, Steve W. Lindsay, Nick Golding, Catherine L. Moyes

Approximately 150 triatomine species are suspected to be infected with the Chagas parasite, Trypanosoma cruzi, but they differ in the risk they pose to human populations. The largest risk comes from species that have a domestic life cycle and these species have been targeted by indoor residual spraying campaigns, which have been successful in many locations. It is now important to consider residual transmission that may be linked to persistent populations of dominant vectors, or to secondary or minor vectors. The aim of this project was to define the geographical distributions of the community of triatomine species across the Chagas endemic region. Presence-only data with over 12, 000 observations of triatomine vectors were extracted from a public database and target-group background data were generated to account for sampling bias in the presence data. Geostatistical regression was then applied to estimate species distributions and fine-scale distribution maps were generated for thirty triatomine vector species including those found within one or two countries and species that are more widely distributed from northern Argentina to Guatemala, Bolivia to southern Mexico, and Mexico to the southern United States of America. The results for Rhodnius pictipes, Panstrongylus geniculatus, Triatoma dimidiata, Triatoma gerstaeckeri, and Triatoma infestans are presented in detail, including model predictions and (un)certainty in these predictions, and the model validation results for each of the 30 species are presented in full. The predictive maps for all species are made publicly available so that they can be used to assess the communities of vectors present within different regions of the endemic zone. The maps are presented alongside key indicators for the capacity of each species to transmit T. cruzi to humans. These indicators include infection prevalence, evidence for human blood meals, and colonisation or invasion of homes. A summary of the published evidence for these indicators shows that the majority of the 30 species mapped by this study have the potential to transmit T. cruzi to humans.

Volcanic activity controls cholera outbreaks in the East African Rift

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

by Doudou Batumbo Boloweti, Patrick Giraudoux, Catherine Deniel, Emmanuel Garnier, Frederic Mauny, Celestin Mahinda Kasereka, Roger Kizungu, Jean Jacques Muyembe, Didier Bompangue, Gudrun Bornette

We hypothesized that Cholera (Vibrio cholerae) that appeared along Lake Kivu in the African Rift in the seventies, might be controlled by volcano-tectonic activity, which, by increasing surface water and groundwater salinity and temperature, may partly rule the water characteristics of Lake Kivu and promote V. cholerae proliferation. Volcanic activity (assessed weekly by the SO2 flux of Nyiragongo volcano plume over the 2007–2012 period) is highly positively correlated with the water conductivity, salinity and temperature of the Kivu lake. Over the 2007–2012 period, these three parameters were highly positively correlated with the temporal dynamics of cholera cases in the Katana health zone that border the lake. Meteorological variables (air temperature and rainfall), and the other water characteristics (namely pH and dissolved oxygen concentration in lake water) were unrelated to cholera dynamics over the same period. Over the 2016–2018 period, we sampled weekly lake water salinity and conductivity, and twice a month vibrio occurrence in lake water and fish. The abundance of V. cholerae in the lake was positively correlated with lake salinity, temperature, and the number of cholera cases in the population of the Katana health zone. V. cholerae abundance in fishes was positively correlated with V. cholerae abundance in lake water, suggesting that their consumption directly contaminate humans. The activity of the volcano, by controlling the physico-chemical characteristics of Lake Kivu, is therefore a major determinant of the presence of the bacillus in the lake. SO2 fluxes in the volcano plume can be used as a tool to predict epidemic risks.

The effectiveness of early start of Grade III response to dengue in Guangzhou, China: A population-based interrupted time-series study

PLoS Neglected Tropical Diseases News - 7 August 2020 - 9:00pm

by Li Li, Wen-Hui Liu, Zhou-Bin Zhang, Yuan Liu, Xiao-Guang Chen, Lei Luo, Chun-Quan Ou

In 2019, dengue incidences increased dramatically in many countries. However, the prospective growth in dengue incidence did not occur in Guangzhou, China. We examined the effectiveness of early start of Grade III response to dengue in Guangzhou. We extracted the data on daily number of dengue cases during 2017–2019 in Guangzhou and weekly data for Foshan and Zhongshan from the China National Notifiable Disease Reporting System, while the data on weekly number of positive ovitraps for adult and larval Aedes albopictus were obtained from Guangzhou Center for Disease Control and Prevention. We estimated the number of dengue cases prevented by bringing forward the starting time of Grade III response from September in 2017–2018 to August in 2019 in Guangzhou using a quasi-Poisson regression model and applied the Baron and Kenny’s approach to explore whether mosquito vector density was a mediator of the protective benefit. In Guangzhou, early start of Grade III response was associated with a decline in dengue incidence (relative risk [RR]: 0.54, 95% confidence interval [CI]: 0.43–0.70), with 987 (95% CI: 521–1,593) cases averted in 2019. The rate of positive ovitraps also significantly declined (RR: 0.64, 95% CI: 0.53–0.77). Moreover, both mosquito vector density and early start of Grade III response was significantly associated with dengue incidence after adjustment for each other. By comparing with the incidence in Foshan and Zhongshan where the Grade III response has not been taken, benefits from the response starting in August were confirmed but not if starting from September. Early start of Grade III response has effectively mitigated the dengue burden in Guangzhou, China, which might be partially through reducing the mosquito vector density. Our findings have important public health implications for development and implementation of dengue control interventions for Guangzhou and other locations with dengue epidemics.

Gravitrap Deployment for Adult <i>Aedes aegypti</i> Surveillance and its Impact on Dengue Cases

PLoS Neglected Tropical Diseases News - 7 August 2020 - 9:00pm

by Janet Ong, Chee-Seng Chong, Grace Yap, Caleb Lee, Muhammad Aliff Abdul Razak, Suzanna Chiang, Lee-Ching Ng

House Index, Container Index, and Breteau Index are the most commonly used indices for dengue vector surveillance. However, these larval indices are a poor proxy for measuring the adult population—which is responsible for disease transmission. Information on the adult distribution and density are important for assessing transmission risk as well as for developing effective control strategies. This study introduces a new entomological index, Gravitrap aegypti index (GAI), which estimates the adult female Aedes aegypti population in the community and presents its association with dengue cases. Gravitraps were deployed across 34 treatment sites in Singapore from September 2013 to September 2016. The GAI, derived from the Gravitrap surveillance data, was analysed to investigate the spatio-temporal patterns of the Ae. aegypti population in Singapore. The index was further categorised into low, moderate, and high-risk groups and its association with dengue cases were examined. A Before-After Control Impact analysis was performed to evaluate the epidemiology impact of Gravitrap system on dengue transmission. The Ae. aegypti population exhibits a seasonal pattern, and spatial heterogeneity in Ae. aegypti abundance was observed among treatment sites. The Ae. aegypti population was also found to be unevenly distributed among floors of an apartment block, with low floors (floors 1–4) having a higher abundance of mosquitoes trapped than mid (floors 5–8) and high (floors ≥9) floors. Areas with high GAI were shown to have higher dengue case count. Gravitrap has also demonstrated to be a good dengue control tool. The contribution of cases by treatment sites to the national numbers was lower after Gravitraps deployment. The GAI, which is of better relevance to dengue transmission risk, could be recommended as an indicator for decision making in vector control efforts, and to monitor the spatio-temporal variability of the adult Aedes population in the country. In addition, findings from this study indicate that Gravitraps can be used as a dengue control tool to reduce dengue transmission.

Lactoferrin is a dynamic protein in human melioidosis and is a TLR4-dependent driver of TNF-α release in <i>Burkholderia thailandensis</i> infection in vitro

PLoS Neglected Tropical Diseases News - 7 August 2020 - 9:00pm

by Shelton W. Wright, Lara Lovelace-Macon, Deirdre Ducken, Sarunporn Tandhavanant, Prapit Teparrukkul, Viriya Hantrakun, Direk Limmathurotsakul, Narisara Chantratita, T. Eoin West

Melioidosis is an often-severe tropical infection caused by Burkholderia pseudomallei (Bp) with high associated morbidity and mortality. Burkholderia thailandensis (Bt) is a closely related surrogate that does not require BSL-3 conditions. Lactoferrin is an iron-binding glycoprotein that can modulate the innate inflammatory response. Here we investigated the impact of lactoferrin on the host immune response in melioidosis. Lactoferrin concentrations were measured in plasma from patients with melioidosis and following ex vivo stimulation of blood from healthy individuals. Bt growth was quantified in liquid media in the presence of purified and recombinant human lactoferrin. Differentiated THP-1 cells and human blood monocytes were infected with Bt in the presence of purified and recombinant human lactoferrin, and bacterial intracellular replication and cytokine responses (tumor necrosis factor-α (TNF-α), interleukin-1β and interferon-γ) were measured. In a cohort of 49 melioidosis patients, non-survivors to 28 days had significantly higher plasma lactoferrin concentrations compared to survivors (median (interquartile range (IQR)): 326 ng/ml (230–748) vs 144 ng/ml (99–277), p<0.001). In blood stimulated with heat-killed Bp, plasma lactoferrin concentration significantly increased compared to unstimulated blood (median (IQR): 424 ng/ml (349–479) vs 130 ng/ml (91–214), respectively; p<0.001). Neither purified nor recombinant human lactoferrin impaired growth of Bt in media. Lactoferrin significantly increased TNF-α production by differentiated THP-1 cells and blood monocytes after Bt infection. This phenotype was largely abrogated when Toll-like receptor 4 (TLR4) was blocked with a monoclonal antibody. Lactoferrin is produced by blood cells after exposure to Bp and lactoferrin concentrations are higher in 28-day survivors in melioidosis. Lactoferrin induces proinflammatory cytokine production after Bt infection that may be TLR4 dependent.

Chikungunya virus requires an intact microtubule network for efficient viral genome delivery

PLoS Neglected Tropical Diseases News - 7 August 2020 - 9:00pm

by Tabitha E. Hoornweg, Ellen M. Bouma, Denise P.I. van de Pol, Izabela A. Rodenhuis-Zybert, Jolanda M. Smit

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus, which has rapidly spread around the globe thereby causing millions of infections. CHIKV is an enveloped virus belonging to the Togaviridae family and enters its host cell primarily via clathrin-mediated endocytosis. Upon internalization, the endocytic vesicle containing the virus particle moves through the cell and delivers the virus to early endosomes where membrane fusion is observed. Thereafter, the nucleocapsid dissociates and the viral RNA is translated into proteins. In this study, we examined the importance of the microtubule network during the early steps of infection and dissected the intracellular trafficking behavior of CHIKV particles during cell entry. We observed two distinct CHIKV intracellular trafficking patterns prior to membrane hemifusion. Whereas half of the CHIKV virions remained static during cell entry and fused in the cell periphery, the other half showed fast-directed microtubule-dependent movement prior to delivery to Rab5-positive early endosomes and predominantly fused in the perinuclear region of the cell. Disruption of the microtubule network reduced the number of infected cells. At these conditions, membrane hemifusion activity was not affected yet fusion was restricted to the cell periphery. Furthermore, follow-up experiments revealed that disruption of the microtubule network impairs the delivery of the viral genome to the cell cytosol. We therefore hypothesize that microtubules may direct the particle to a cellular location that is beneficial for establishing infection or aids in nucleocapsid uncoating.

<i>Fasciola hepatica</i> Serine Protease Inhibitor Family (Serpins): Purposely crafted for regulating host proteases

PLoS Neglected Tropical Diseases News - 6 August 2020 - 9:00pm

by Carolina De Marco Verissimo, Heather L. Jewhurst, Irina G. Tikhonova, Rolf T. Urbanus, Aaron G. Maule, John P. Dalton, Krystyna Cwiklinski

Serine protease inhibitors (serpins) regulate proteolytic events within diverse biological processes, including digestion, coagulation, inflammation and immune responses. The presence of serpins in Fasciola hepatica excretory-secretory products indicates that the parasite exploits these to regulate proteases encountered during its development within vertebrate hosts. Interrogation of the F. hepatica genome identified a multi-gene serpin family of seven members that has expanded by gene duplication and divergence to create an array of inhibitors with distinct specificities. We investigated the molecular properties and functions of two representatives, FhSrp1 and FhSrp2, highly expressed in the invasive newly excysted juvenile (NEJ). Consistent with marked differences in the reactive centre loop (RCL) that executes inhibitor-protease complexing, the two recombinant F. hepatica serpins displayed distinct inhibitory profiles against an array of mammalian serine proteases. In particular, rFhSrp1 efficiently inhibited kallikrein (Ki = 40 nM) whilst rFhSrp2 was a highly potent inhibitor of chymotrypsin (Ki = 0.07 nM). FhSrp1 and FhSrp2 are both expressed on the NEJ surface, predominantly around the oral and ventral suckers, suggesting that these inhibitors protect the parasites from the harmful proteolytic effects of host proteases, such as chymotrypsin, during invasion. Furthermore, the unusual inhibition of kallikrein suggests that rFhSrp1 modulates host responses such as inflammation and vascular permeability by interfering with the kallikrein-kinin system. A vaccine combination of rFhSrp1 and rFhSrp2 formulated in the adjuvant Montanide ISA 206VG elicited modest but non-significant protection against a challenge infection in a rat model, but did induce some protection against liver pathogenesis when compared to a control group and a group vaccinated with two well-studied vaccine candidates, F. hepatica cathepsin L2 and L3. This work highlights the importance of F. hepatica serpins to regulate host responses that enables parasite survival during infection and, coupled with the vaccine data, encourages future vaccine trials in ruminants.

SARS-CoV-2 infection in China—Before the pandemic

PLoS Neglected Tropical Diseases News - 6 August 2020 - 9:00pm

by Huiying Liang, Lingling Zheng, Huimin Xia, Jinling Tang

In order to rapidly inform polices in the international response to the ongoing pandemic of coronavirus disease 19 (COVID-19), we summarize in this review current evidence on epidemiological and clinical features of the infection, transmission routes, problems of nucleic-acid testing, the epidemiological trend in China and impact of interventional measures, and some lessons learned. We concluded that the epidemic is containable with traditional nonpharmacological interventions, mainly through social distancing and finding and isolating suspected patients and close contacts. Nonpharmacological interventions are the only effective measures currently accessible and have suppressed some 90% of the infections in China. Close contacts are the major mechanism of transmission, which makes it possible to control this epidemic through nonpharmacological methods. Nucleic-acid testing alone may miss some 50% of infected patients, and other methods such as chest computerized tomography (CT) or serology should be considered to supplement molecular testing. The development of vaccines and drugs is important, but hesitation to make use of nonpharmacological interventions may mean missing golden opportunities for effective actions.

Recalcitrant eumycetoma of the foot: Financial burden a major barrier on the road of recovery

PLoS Neglected Tropical Diseases News - 6 August 2020 - 9:00pm

by Gagandeep Singh, Reshu Agarwal, Swati Khullar, Immaculata Xess, Vinod Kumar Sharma, Ankur Goyal