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The macrophage microtubule network acts as a key cellular controller of the intracellular fate of <i>Leishmania infantum</i>

PLoS Neglected Tropical Diseases News - 28 July 2020 - 9:00pm

by Sandrine Cojean, Valérie Nicolas, Vanessa Lievin-Le Moal

The parasitophorous vacuoles (PVs) that insulate Leishmania spp. in host macrophages are vacuolar compartments wherein promastigote forms differentiate into amastigote that are the replicative form of the parasite and are also more resistant to host responses. We revisited the biogenesis of tight-fitting PVs that insulate L. infantum in promastigote-infected macrophage-like RAW 264.7 cells by time-dependent confocal laser multidimensional imaging analysis. Pharmacological disassembly of the cellular microtubule network and silencing of the dynein gene led to an impaired interaction of L. infantum-containing phagosomes with late endosomes and lysosomes, resulting in the tight-fitting parasite-containing phagosomes never transforming into mature PVs. Analysis of the shape of the L. infantum parasite within PVs, showed that factors that impair promastigote-amastigote differentiation can also result in PVs whose maturation is arrested. These findings highlight the importance of the MT-dependent interaction of L. infantum-containing phagosomes with the host macrophage endolysosomal pathway to secure the intracellular fate of the parasite.

Screening of insecticide resistance in <i>Aedes aegypti</i> populations collected from parishes in Eastern Jamaica

PLoS Neglected Tropical Diseases News - 27 July 2020 - 9:00pm

by Sheena Francis, Towanna Campbell, Sashell McKenzie, Danisha Wright, Jervis Crawford, Trevann Hamilton, Sherine Huntley-Jones, Simone Spence, Allison Belemvire, Kristen Alavi, Carolina Torres Gutierrez

Owing to the increased reports in Aedes-borne diseases in the Caribbean and Latin America, the United States Agency for International Development assisted the Jamaican Ministry of Health and Wellness in conducting insecticide susceptibility tests on Aedes aegypti populations. Sentinel sites were established in seven parishes of Jamaica (St. Catherine, Kingston and St. Andrew, St. Thomas, Portland, St. Mary and St. Ann) and Aedes aegypti eggs were collected, reared to adults per collected population and their susceptibility to varying pyrethroids and organophosphates were tested using the World Health Organization paper bioassays for these insecticides. The Centers for Disease Control and Prevention bottle bioassay was used to assess susceptibility to the carbamate, bendiocarb. The voltage gated sodium channel gene mutations V1016I and I1011V, normally associated with pyrethroid resistance, were also analysed. The results showed that Aedes aegypti collected from all parishes exhibited resistance to pyrethroids at the following concentrations, permethrin 0.25–2.5%; deltamethrin 0.03–0.15%; lambda-cyhalothrin 0.03–0.3%; and etofenprox 0.5–2.5%. The insecticide deltamethrin at concentration 0.3% was the only pyrethroid tested that resulted in high mortality, 94.9 ± 0.34% knockdown within 1 hour of exposure and 98.95 ± 0.01% mortality (p <0.01) at 24 hours post exposure. The frequency of the voltage gated sodium channel gene mutation V1016I was high in the tested population, possibly accounting for the reduced sensitivity to pyrethroids. Organophosphate resistance was also observed in all populations tested. Mortality rates for 0.8% Malathion was 0.8 ± 0.02–60.68 ± 0.01% after 24 hour and 0.00–47.10 ± 0.09%, for pirimiphos-methyl 0.21%. Bendiocarb applied as 12.5 μg/ bottle resulted in mortality rates of 76.25 ± 4.30–100 ± 0.00% after 30 minutes of exposure. The results showed that Ae. aegypti from the seven parishes analysed demonstrated resistance to the insecticides tested. Deltamethrin and bendiocarb at concentrations 0.3% and 12.5μg respectively, were considered most effective, causing high mortality in the local populations. Routine monitoring and evaluations of Ae. aegypti populations from the included parishes are recommended. Additionally, the study results represent the most comprehensive testing to date with local Aedes aegypti populations distributed across different parishes of Jamaica and should be useful to guide national and sub national strategies for vector control and surveillance.

Gene design, optimization of protein expression and preliminary evaluation of a new chimeric protein for the serological diagnosis of both human and canine visceral leishmaniasis

PLoS Neglected Tropical Diseases News - 27 July 2020 - 9:00pm

by Wagner J. T. Santos, Diego H. C. Tavares, Artur L. Castro Neto, Marília B. Nascimento, Rafael Dhalia, Alessandra L. Albuquerque, Carlos H. N. Costa, Franklin B. Magalhães, Antônio M. Rezende, Osvaldo P. de Melo Neto

Background

Visceral leishmaniasis (VL) is a major neglected disease, potentially fatal, whose control is still impaired by inefficient and/or expensive treatment and diagnostic methods. The most promising approach for VL diagnosis uses serological assays with recombinant proteins, since they are more efficient and easier to perform. Tests developed for the human form of the disease, however, have not been shown to be efficient for its diagnosis in the canine host, the major reservoir for the American VL.

Methodology/Principal findings

Here, we describe a systematic approach aimed at the production of a new chimeric protein potentially able to be used for both human and canine VL diagnosis and based both on in silico gene design and experimental data. Starting from the previous identification of Leishmania infantum recombinant antigens efficient for the diagnosis of either human or canine VL, three of the best performing antigens were selected (Lci2, Lci3 and Lci12). After a preliminary evaluation validating the chimeric approach, DNA fragments encoding predicted antigenic regions from each protein, enriched with repeats, were joined in various combinations to generate a total of seventeen chimeric genes optimized for prokaryotic expression. These were assessed for optimal expression and purification yield, with four chimeric proteins being efficiently produced. Their diagnostic potential was then evaluated through ELISA assays with sera from VL afflicted humans and dogs. After two rounds of gene design, the results showed high levels of sensitivity for the best chimeric protein, named Q5, in humans (82%) and dogs (100%) with 100% specificity in comparison with healthy controls. A single non-specific reaction was seen with serum from individuals with tegumentary leishmaniasis.

Conclusion

The newly described chimeric protein is potentially useful for the detection of both humans and dogs afflicted with VL, with its use in rapid tests necessary for validation as a new diagnostic tool.

Non-invasive monitoring of drug action: A new live <i>in vitro</i> assay design for Chagas’ disease drug discovery

PLoS Neglected Tropical Diseases News - 27 July 2020 - 9:00pm

by Anna F. Fesser, Olivier Braissant, Francisco Olmo, John M. Kelly, Pascal Mäser, Marcel Kaiser

New assay designs are needed to improve the predictive value of the Trypanosoma cruzi in vitro tests used as part of the Chagas' disease drug development pipeline. Here, we employed a green fluorescent protein (eGFP)-expressing parasite line and live high-content imaging to monitor the growth of T. cruzi amastigotes in mouse embryonic fibroblasts. A novel assay design allowed us to follow parasite numbers over 6 days, in four-hour intervals, while occupying the microscope for only 24 hours per biological replicate. Dose-response curves were calculated for each time point after addition of test compounds, revealing how EC50 values first decreased over the time of drug exposure, and then leveled off. However, we observed that parasite numbers could vary, even in the untreated controls, and at different sites in the same well, which caused variability in the EC50 values. To overcome this, we established that fold change in parasite number per hour is a more robust and informative measure of drug activity. This was calculated based on an exponential growth model for every biological sample. The net fold change per hour is the result of parasite replication, differentiation, and death. The calculation of this fold change enabled us to determine the tipping point of drug action, i.e. the time point when the death rate of the parasites exceeded the growth rate and the fold change dropped below 1, depending on the drug concentration and exposure time. This revealed specific pharmacodynamic profiles of the benchmark drugs benznidazole and posaconazole.

Health services uptake among nomadic pastoralist populations in Africa: A systematic review of the literature

PLoS Neglected Tropical Diseases News - 27 July 2020 - 9:00pm

by Victoria M. Gammino, Michael R. Diaz, Sarah W. Pallas, Abigail R. Greenleaf, Molly R. Kurnit

The estimated 50 million nomadic pastoralists in Africa are among the most “hard-to-reach” populations for health-service delivery. While data are limited, some studies have identified these communities as potential disease reservoirs relevant to neglected tropical disease programs, particularly those slated for elimination and eradication. Although previous literature has emphasized the role of these populations’ mobility, the full range of factors influencing health service utilization has not been examined systematically. We systematically reviewed empirical literature on health services uptake among African nomadic pastoralists from seven online journal databases. Papers meeting inclusion criteria were reviewed using STROBE- and PRISMA-derived guidelines. Study characteristics were summarized quantitatively, and 10 key themes were identified through inductive qualitative coding. One-hundred two papers published between 1974–2019 presenting data from 16 African countries met our inclusion criteria. Among the indicators of study-reporting quality, limitations (37%) and data analysis were most frequently omitted (18%) We identified supply- and demand-side influences on health services uptake that related to geographic access (79%); service quality (90%); disease-specific knowledge and awareness of health services (59%); patient costs (35%); contextual tailoring of interventions (75%); social structure and gender (50%); subjects’ beliefs, behaviors, and attitudes (43%); political will (14%); and social, political, and armed conflict (30%) and community agency (10%). A range of context-specific factors beyond distance to facilities or population mobility affects health service uptake. Approaches tailored to the nomadic pastoralist lifeway, e.g., that integrated human and veterinary health service delivery (a.k.a., “One Health”) and initiatives that engaged communities in program design to address social structures were especially promising. Better causal theorization, transdisciplinary and participatory research methods, clearer operational definitions and improved measurement of nomadic pastoralism, and key factors influencing uptake, will improve our understanding of how to increase accessibility, acceptability, quality and equity of health services to nomadic pastoralist populations.

Real-time dengue forecast for outbreak alerts in Southern Taiwan

PLoS Neglected Tropical Diseases News - 27 July 2020 - 9:00pm

by Yu-Chieh Cheng, Fang-Jing Lee, Ya-Ting Hsu, Eric V. Slud, Chao A. Hsiung, Chun-Hong Chen, Ching-Len Liao, Tzai-Hung Wen, Chiu-Wen Chang, Jui-Hun Chang, Hsiao-Yu Wu, Te-Pin Chang, Pei-Sheng Lin, Hui-Pin Ho, Wen-Feng Hung, Jing-Dong Chou, Hsiao-Hui Tsou

Dengue fever is a viral disease transmitted by mosquitoes. In recent decades, dengue fever has spread throughout the world. In 2014 and 2015, southern Taiwan experienced its most serious dengue outbreak in recent years. Some statistical models have been established in the past, however, these models may not be suitable for predicting huge outbreaks in 2014 and 2015. The control of dengue fever has become the primary task of local health agencies. This study attempts to predict the occurrence of dengue fever in order to achieve the purpose of timely warning. We applied a newly developed autoregressive model (AR model) to assess the association between daily weather variability and daily dengue case number in 2014 and 2015 in Kaohsiung, the largest city in southern Taiwan. This model also contained additional lagged weather predictors, and developed 5-day-ahead and 15-day-ahead predictive models. Our results indicate that numbers of dengue cases in Kaohsiung are associated with humidity and the biting rate (BR). Our model is simple, intuitive and easy to use. The developed model can be embedded in a "real-time" schedule, and the data (at present) can be updated daily or weekly based on the needs of public health workers. In this study, a simple model using only meteorological factors performed well. The proposed real-time forecast model can help health agencies take public health actions to mitigate the influences of the epidemic.

Occurrence of multiple genotype infection caused by <i>Leishmania infantum</i> in naturally infected dogs

PLoS Neglected Tropical Diseases News - 27 July 2020 - 9:00pm

by Elisa Cupolillo, Amanda S. Cavalcanti, Gabriel Eduardo Melim Ferreira, Mariana Côrtes Boité, Fernanda Nazaré Morgado, Renato Porrozzi

Genetic polymorphisms in natural Leishmania populations have been reported in endemic areas. Microsatellite typing is a useful tool to elucidate the genetic variability of parasite strains, due to its capability for high-resolution mapping of genomic targets. The present study employed multilocus microsatellite typing (MLMT) to explore the genotypic composition of Leishmania infantum in naturally infected dogs by genotyping parasites infecting different tissues with or without in vitro expansion. Eighty-six samples were collected from 46 animals in an endemic region of visceral leishmaniasis (VL). MLMT was performed for 38 spleen samples and 48 L. infantum cultures isolated from different tissues. Of the 86 samples, 23 were effectively genotyped by MLMT, identifying nine multilocus genotypes (MLG; referred to as MLG A–I). MLGs A, B and C were detected in more than one type of tissue and in more than one sample. Conversely, MLG D-I were uniquely detected in one sample each. The results showed that multiple genotype infections occur within a single host and tissue. Paired sample analysis revealed the presence of different MLMT alleles in 14 dogs, while the same MLG allele was present in 15 animals. STRUCTURE analysis demonstrated the presence of two populations; 13 samples displayed a similar admixture of both ancestral populations, and these were not assigned to any population. Only samples for which Q ≥ 0.70 after CLUMPP alignment were considered to be part of Population 1 (POP1) or Population 2 (POP2). POP2 comprised the majority of samples (n = 54) compared to POP1 (n = 19). This study presents evidence of multiple genotype infections (caused by L. infantum) in dogs in an area with high VL transmission. Further investigations must be undertaken to determine the multiple effects of infection on the host immune response and disease dynamics and treatment.

Genetic tools discriminate strains of <i>Leishmania infantum</i> isolated from  humans and dogs in Sicily, Italy

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

by Germano Castelli, Federica Bruno, Valentina Caputo, Santi Fiorella, Ignazio Sammarco, Tiziana Lupo, Antonella Migliazzo, Fabrizio Vitale, Stefano Reale

Background

Leishmaniasis is one of the most important vector-borne diseases and it represents a serious world health problem affecting millions of people. High levels of Leishmania infections, affecting both humans and animals, are recognized among Italian regions. Among these, Sicily has one of the highest prevalence of Leishmania infection.

Methodology/Principal Findings

Seventy-eight Leishmania strains isolated from human and animal samples across Sicily, were analyzed for the polymorphic k26-gene and genotypes were assigned according to the size of the PCR products. A multilocus microsatellite typing (MLMT) approach based on the analysis of 11 independent loci was used to investigate populations structure and genetic diversity of the isolated strains. Six L. infantum reference strains were included in the analysis for comparison. Bayesian clustering analysis of microsatellite data showed that all the isolated strains clustered in two genetically distinct populations, corresponding to human and canine isolates respectively. A further subdivision was observed between the two main groups, giving a good correlation between human strains and their geographic origin, conversely canine population showed a great genetic variability diffused in the territory.

Conclusions/Significance

Among the 78 Leishmania isolates, K26 analysis detected 71 samples (91%) as MON-1 zymodeme, confirming it as the predominant strain in Mediterranean area and 7 human samples (9%) as non-MON-1. MLMT gives important insights into the epidemiology of leishmaniases and allows characterization of different strains to a higher resolution than possible with zymodeme typing. Two main populations presented a strong correlation respect to the different hosts, exhibiting a co-circulation of two distinct populations of L. infantum. The population found in infected humans exhibited a correlation with geographic origin. These clusters could represent a geographically restricted population of strains with the same or related genotypes. This study can contribute to an understanding of Leishmania epidemiology, including the spread of reservoirs and sand fly vectors in the different foci of infection, characterizing parasites within the different hosts.

Brucellosis in ruminants and pastoralists in Borena, Southern Ethiopia

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

by Bedaso Mammo Edao, Gobena Ameni, Zerihun Assefa, Stefan Berg, Adrian M. Whatmore, James L. N. Wood

Brucellosis is a bacterial zoonotic disease that has important veterinary and public health consequences as well as economic impact in sub Saharan Africa including Ethiopia. A cross-sectional study was conducted in four selected districts of Borena Pastoral setting in Southern Ethiopia from October 2017 to February 2018 to estimate the prevalence of brucellosis and assess associated risk factors in cattle, sheep, goats and occupationally associated humans. A total of 750 cattle, 882 sheep and goats and 341 human subjects were screened for evidence of brucellosis using the Rose Bengal Test (RBT) with positive results confirmed by Competitive-ELISA(c-ELISA). Structured questionnaires were used for collection of metadata from individual animals, herders and animal attendants to test the association between explanatory and outcome variables. The overall animal level prevalence was 2.4% (95% confidence interval, CI: 1.4–3.7) in cattle, 3.2% (95% CI: 2.1–4.6) in sheep and goats, and 2.6% (95% CI: 1.2–5) in humans occupationally linked to livestock production systems. Herd size, parity, and history of abortion were risk factors associated with Brucella seropositivity (P<0.05) in cattle whereas in sheep and goats the results showed that district, age group, flock size, and history of abortion were significantly associated risk factors with Brucella seropositivity (P<0.05). Assisting calving and presence of seropositive animals in a household (P<0.05) were significantly associated with Brucella seropositivity in humans. Evidence of brucellosis in various animal species and the associated human population illustrates the need for a coordinated One Health approach to controlling brucellosis so as to improve public health and livestock productivity.

Understanding leptospirosis eco-epidemiology by environmental DNA metabarcoding of irrigation water from two agro-ecological regions of Sri Lanka

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

by Chandika D. Gamage, Yukuto Sato, Ryosuke Kimura, Tetsu Yamashiro, Claudia Toma

Background

Leptospirosis is one of the most significant zoonoses across the world not only because of its impact on human and animal health but also because of the economic and social impact on agrarian communities. Leptospirosis is endemic in Sri Lanka where paddy farming activities, the use of draught animals in agriculture, and peridomestic animals in urban and rural areas play important roles in maintaining the infection cycle of pathogenic Leptospira, especially concerning animals as a potential reservoir. In this study, an environmental DNA (eDNA) metabarcoding methodology was applied in two different agro-ecological regions of Sri Lanka to understand the eco-epidemiology of leptospirosis.

Methodology/Principal findings

Irrigation water samples were collected in Kandy District (wet zone mid-country region 2) and Girandurukotte, Badulla District (intermediate zone low-country region 2); and analysed for the presence of pathogenic Leptospira, associated microbiome and the potential reservoir animals. Briefly, we generated PCR products for high-throughput sequencing of multiple amplicons through next-generation sequencing. The analysis of eDNA showed different environmental microbiomes in both regions and a higher diversity of Leptospira species circulating in Kandy than in Girandurukotte. Moreover, the number of sequence reads of pathogenic Leptospira species associated with clinical cases such as L. interrogans was higher in Kandy than in Girandurukotte. Kandy also showed more animal species associated with pathogenic bacterial species than Girandurukotte. Finally, several pathogenic bacterial species including Arcobacter cryaerophilus, responsible for abortion in animals, was shown to be associated with pathogenic Leptospira.

Conclusions/Significance

Leptospirosis has been considered to be endemic in wet regions, consistently, leptospiral sequences were detected strongly in Kandy. The great Leptospira species diversity in Kandy observed in this study shows that the etiological agents of leptospirosis in Sri Lanka might be underestimated. Furthermore, our eDNA metabarcoding can be used to discriminate bacterial and animal species diversity in different regions and to explore environmental microbiomes to identify other associated bacterial pathogens in the environment.

Marginalized mites: Neglected vectors of neglected diseases

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

by Thomas Weitzel, Benjamin L. Makepeace, Ivo Elliott, Kittipong Chaisiri, Allen L. Richards, Paul N. Newton

Behavioral and structural barriers to accessing human post-exposure prophylaxis and other preventive practices in Arequipa, Peru, during a canine rabies epidemic

PLoS Neglected Tropical Diseases News - 21 July 2020 - 9:00pm

by Ricardo Castillo-Neyra, Alison M. Buttenheim, Joanna Brown, James F. Ferrara, Claudia Arevalo-Nieto, Katty Borrini-Mayorí, Michael Z. Levy, Victor Becerra, Valerie A. Paz-Soldan

A canine rabies epidemic started in early 2015 in Arequipa, Peru and the rabies virus continues to circulate in the dog population. Some city residents who suffer dog bites do not seek care or do not complete indicated post-exposure prophylaxis (PEP) regimens, increasing the risk of human rabies. The objectives of our study are to qualitatively assess knowledge about rabies, and preventive practices, such as rabies vaccine administration, following a dog bite. We conduct eight focus group discussions in peri-urban and urban communities with 70 total participants. In our results, we observe low awareness of rabies severity and fatality, and different practices following a dog bite, depending on the community type: for example, whereas participants in the urban communities report cleaning the wound with hydrogen peroxide rather than soap and water, participants in peri-urban areas cover the wound with herbs and hair from the dog that bit them. Misconceptions about rabies vaccines and mistreatment at health centers also commonly prevent initiating or completing PEP. We identify important behavioral and structural barriers and knowledge gaps that limit evidence-based preventive strategies against rabies and may threaten successful prevention of dog-mediated human rabies in this setting.

A clinical scoring system to predict long-term arthralgia in Chikungunya disease: A cohort study

PLoS Neglected Tropical Diseases News - 21 July 2020 - 9:00pm

by Laise de Moraes, Thiago Cerqueira-Silva, Victor Nobrega, Kevan Akrami, Luciane Amorim Santos, Cibele Orge, Paula Casais, Lais Cambui, Rita de Cássia Pontello Rampazzo, Karen Soares Trinta, Camila Amato Montalbano, Maria Jania Teixeira, Luciano Pamplona Cavalcante, Bruno B. Andrade, Rivaldo Venâncio da Cunha, Marco Aurélio Krieger, Manoel Barral-Netto, Aldina Barral, Ricardo Khouri, Viviane Sampaio Boaventura

Background

Chikungunya virus (CHIKV) has caused worldwide epidemics that impose a major burden on health systems. Approximately half of infected individuals develop chronic debilitating arthralgia, affecting their quality of life. Here, we identified the relevant clinical and demographic variables in the acute phase of CHIKV infection prospectively linked to chronic arthralgia to elaborate a prognostic scoring system.

Methods

Acute CHIKV infection cases (n = 134) confirmed by serology or molecular test were examined <10 days of disease onset and followed for one year to evaluate for disease progression. Potential risk factors for chronic arthralgia were evaluated by multivariate analysis to develop a prognostic scoring system, which was subsequently tested in an independent validation cohort consisting of 42 individuals.

Results

A total of 107 out of 134 (80%) acute CHIKV-confirmed cases from the derivation cohort were re-examined one year after enrollment. Chronic arthralgia post-CHIKV infection was diagnosed in 64 (60%). Five of the 12 parameters evaluated in the acute phase were statistically associated with persistent arthralgia and were further tested by Bayesian analysis. These variables were weighted to yield a prognosis score denominated SHERA (Sex, Hypertension, Edema, Retroocular pain, Age), which exhibited 81.3% accuracy in predicting long-term arthralgia post-CHIKV infection in the derivation cohort, and 76.5% accuracy in the validation cohort.

Conclusions

The simplified and externally validated prognostic scoring system, SHERA, is a useful method to screen acutely CHIKV-infected patients at elevated risk of chronic arthralgia who will benefit from specific interventions. This tool could guide public health policies, particularly in resource-constrained settings.

Quantifying sociodemographic heterogeneities in the distribution of <i>Aedes aegypti</i> among California households

PLoS Neglected Tropical Diseases News - 21 July 2020 - 9:00pm

by Marisa A. P. Donnelly, Susanne Kluh, Robert E. Snyder, Christopher M. Barker

The spread of Aedes aegypti in California and other regions of the U.S. has increased the need to understand the potential for local chains of Ae. aegypti-borne virus transmission, particularly in arid regions of the state where the ecology of these mosquitoes is less understood. For public health and vector control programs, it is helpful to know whether variation in risk of local transmission can be attributed to socio-demographic factors that could help to target surveillance and control programs. Socio-demographic factors have been shown to influence transmission risk of dengue virus outside the U.S. by modifying biting rates and vector abundance. In regions of the U.S. where Ae. aegypti have recently invaded and where residential areas are structured differently than those in the tropics where Ae. aegypti are endemic, it is unclear how socio-demographic factors modify the abundance of Ae. aegypti populations. Understanding heterogeneities among households in Ae. aegypti abundance will provide a better understanding of local vectorial capacity and is an important component of understanding risk of local Ae. aegypti-borne virus transmission. We conducted a cross-sectional study in Los Angeles County, California during summer 2017 to understand the causes of variation in relative abundance of Ae. aegypti among households. We surveyed 161 houses, representing a wide range of incomes. Surveys consisted of systematic adult mosquito collections, inspections of households and properties, and administration of a questionnaire in English or Spanish. Adult Ae. aegypti were detected at 72% of households overall and were found indoors at 12% of households. An average of 3.1 Ae. aegypti were collected per household. Ae. aegypti abundance outdoors was higher in lower-income neighborhoods and around older households with larger outdoor areas, greater densities of containers with standing water, less frequent yard maintenance, and greater air-conditioner use. We also found that Aedes aegypti abundance indoors was higher in households that had less window and door screening, less air-conditioner usage, more potted plants indoors, more rain-exposed containers around the home, and lower neighborhood human population densities. Our results indicate that, in the areas of southern California studied, there are behavioral and socio-demographic determinants of Ae. aegypti abundance, and that low-income households could be at higher risk for exposure to Ae. aegypti biting and potentially greater risk for Zika, dengue, and chikungunya virus transmission if a local outbreak were to occur.

Characterization of a dual-action adulticidal and larvicidal interfering RNA pesticide targeting the <i>Shaker</i> gene of multiple disease vector mosquitoes

PLoS Neglected Tropical Diseases News - 20 July 2020 - 9:00pm

by Keshava Mysore, Limb K. Hapairai, Longhua Sun, Ping Li, Chien-Wei Wang, Nicholas D. Scheel, Alexandra Lesnik, Jessica Igiede, Max P. Scheel, Na Wei, David W. Severson, Molly Duman-Scheel

The existing mosquito pesticide repertoire faces great challenges to sustainability, and new classes of pesticides are vitally needed to address established and emerging mosquito-borne infectious diseases. RNA interference- (RNAi-) based pesticides are emerging as a promising new biorational mosquito control strategy. In this investigation, we describe characterization of an interfering RNA pesticide (IRP) corresponding to the mosquito Shaker (Sh) gene, which encodes an evolutionarily conserved voltage-gated potassium channel subunit. Delivery of the IRP to Aedes aegypti adult mosquitoes in the form of siRNA that was injected or provided as an attractive toxic sugar bait (ATSB) led to Sh gene silencing that resulted in severe neural and behavioral defects and high levels of adult mortality. Likewise, when provided to A. aegypti larvae in the form of short hairpin RNA (shRNA) expressed in Saccharomyces cerevisiae (baker’s yeast) that had been formulated into a dried inactivated yeast tablet, the yeast IRP induced neural defects and larval death. Although the Sh IRP lacks a known target site in humans or other non-target organisms, conservation of the target site in the Sh genes of multiple mosquito species suggested that it may function as a biorational broad-range mosquito insecticide. In support of this, the Sh IRP induced both adult and larval mortality in treated Aedes albopictus, Anopheles gambiae, and Culex quinquefasciatus mosquitoes, but was not toxic to non-target arthropods. These studies indicated that IRPs targeting Sh could one day be used in integrated biorational mosquito control programs for the prevention of multiple mosquito-borne illnesses. The results of this investigation also suggest that the species-specificity of ATSB technology, a new paradigm for vector control, could be enhanced through the use of RNAi-based pesticides.

Atypical memory B-cells and autoantibodies correlate with anemia during <i>Plasmodium vivax</i> complicated infections

PLoS Neglected Tropical Diseases News - 20 July 2020 - 9:00pm

by Juan Rivera-Correa, Maria Fernanda Yasnot-Acosta, Nubia Catalina Tovar, María Camila Velasco-Pareja, Alice Easton, Ana Rodriguez

Malaria caused by Plasmodium vivax is a highly prevalent infection world-wide, that was previously considered mild, but complications such as anemia have been highly reported in the past years. In mice models of malaria, anti-phosphatidylserine (anti-PS) autoantibodies, produced by atypical B-cells, bind to uninfected erythrocytes and contribute to anemia. In human patients with P. falciparum malaria, the levels of anti-PS, atypical B-cells and anemia are strongly correlated to each other. In this study, we focused on assessing the relationship between autoantibodies, different B-cell populations and hemoglobin levels in two different cohorts of P. vivax patients from Colombia, South America. In a first longitudinal cohort, our results show a strong inverse correlation between different IgG autoantibodies tested (anti-PS, anti-DNA and anti-erythrocyte) and atypical memory B-cells (atMBCs) with hemoglobin in both P. vivax and P. falciparum patients over time. In a second cross-sectional cohort, we observed a stronger relation between hemoglobin levels, atMBCs and autoantibodies in complicated P. vivax patients compared to uncomplicated ones. Altogether, these data constitute the first evidence of autoimmunity associating with anemia and complicated P. vivax infections, suggesting a role for its etiology through the expansion of autoantibody-secreting atMBCs.

Long-term incidence of relapse and post-kala-azar dermal leishmaniasis after three different visceral leishmaniasis treatment regimens in Bihar, India

PLoS Neglected Tropical Diseases News - 20 July 2020 - 9:00pm

by Vishal Goyal, Vidya Nand Rabi Das, Shambhu Nath Singh, Ravi Shankar Singh, Krishna Pandey, Neena Verma, Allen Hightower, Suman Rijal, Pradeep Das, Jorge Alvar, Caryn Bern, Fabiana Alves

Background

Few prospective data exist on incidence of post kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis (VL) relapse after different treatment regimens.

Methodology/Principal findings

A Phase IV trial included 1761 VL patients treated between 2012–2014 with single dose AmBisome (SDA; N = 891), miltefosine-paromomycin (Milt-PM; n = 512), or AmBisome-miltefosine (AmB-Milt; n = 358). Follow-up for PKDL and VL relapse was scheduled for 6, 12 and 24 months after treatment, lasting until 2017. Patients with lesions consistent with PKDL were tested by rK39 rapid test, and if positive, underwent skin-snip sampling, smear microscopy and PCR. Probable PKDL was defined by consistent lesions and positive rK39; confirmed PKDL required additional positive microscopy or PCR. PKDL and relapse incidence density were calculated by VL treatment and risk factors evaluated in Cox proportional hazards models.Among 1,750 patients who completed treatment, 79 had relapse and 104 PKDL. Relapse incidence density was 1.58, 2.08 and 0.40 per 1000 person-months for SDA, AmB-Milt and Milt-PM, respectively. PKDL incidence density was 1.29, 1.45 and 2.65 per 1000 person-months for SDA, AmB-Milt and Milt-PM. In multivariable models, patients treated with Milt-PM had lower relapse but higher PKDL incidence than those treated with SDA; AmB-Milt rates were not significantly different from those for SDA. Children <12 years were at higher risk for both outcomes; females had a higher risk of PKDL but not relapse.

Conclusions/Significance

Active surveillance for PKDL and relapse, followed by timely treatment, is essential to sustain the achievements of VL elimination programs in the Indian sub-continent.

Fast recovery of house infestation with <i>Triatoma brasiliensis</i> after residual insecticide spraying in a semiarid region of Northeastern Brazil

PLoS Neglected Tropical Diseases News - 20 July 2020 - 9:00pm

by Claudia Mendonça Bezerra, Silvia Ermelinda Barbosa, Rita de Cássia Moreira de Souza, Levi Ximenes Feijão, Ricardo Esteban Gürtler, Alberto Novaes Ramos Jr, Liléia Diotaiuti

The northeastern semiarid region stands out in the Brazilian context regarding the eco-epidemiology of Chagas disease, in which Triatoma brasiliensis is the main vector of Trypanosoma cruzi. Persistent house invasion threatens the relative levels of progress achieved over previous decades. We conducted an intervention trial with a five-year follow-up to assess the impacts of residual spraying with pyrethroid insecticides on house infestation with T. brasiliensis in 18 rural villages (242 houses) located in the Tauá, Ceará. House infestations were assessed by systematic manual searches for triatomines in every domestic and peridomestic habitat on five occasions. Triatomines were collected in peridomestic (57.5%), sylvatic (35.8%), and intradomiciliary (6.7%) habitats. The most important ecotopes of T. brasiliensis were containing roofing tiles, bricks or rocks (23.4% ± 9.1). Residual insecticide spraying substantially reduced baseline house infestation rates from 27.9% to 5.9% by 6 months post first spraying (MPS). The decline was substantially greater in intradomiciles (11.2% to 0.8%) than in peridomiciles (16.7% to 5%). The mean relative density of triatomines recovered its preintervention values at 14 MPS in intradomiciles, and in the main peridomestic ecotopes. The house infestation levels recorded at 14 MPS persisted thereafter despite all reinfested houses were selectively sprayed on every occasion. Overall average bug infection rates with T. cruzi in the five occasions were in intradomiciles (11.1%), peridomiciles (4.7%) and wild habitats (3.3%). In peridomicile T. cruzi infection rates decreased significantly at all stages after chemical intervention. In intradomicile, the only significant difference occurred at 20 MPS (7.7% to 30.8%). The vectorial capacity of T. brasiliensis, combined with its invasive potential from sylvatic sources and the limited effectiveness of chemical control in the harsh caatinga landscape, pose serious obstacles to the definite elimination of domestic transmission risks. Systematic vector surveillance supported by community participation and locally adapted environmental management measures are needed to reduce the risks of establishment of domestic transmission with T. cruzi in this region.

Serological evidence of exposure to Rift Valley, Dengue and Chikungunya Viruses among agropastoral communities in Manyara and Morogoro regions in Tanzania: A community survey

PLoS Neglected Tropical Diseases News - 20 July 2020 - 9:00pm

by Rule M. Budodo, Pius G. Horumpende, Sixbert I. Mkumbaye, Blandina T. Mmbaga, Richard S. Mwakapuja, Jaffu O. Chilongola

Tanzania has recently experienced outbreaks of dengue in two coastal regions of Dar es Salaam and Tanga. Chikungunya and Rift Valley Fever outbreaks have also been recorded in the past decade. Little is known on the burden of the arboviral disease causing viruses (Dengue, Rift Valley and Chikungunya) endemically in the inter-epidemic periods. We aimed at determining the prevalence of the dengue, rift valley and chikungunya among humans in two geo ecologically distinct sites. The community-based cross-sectional study was conducted in Magugu in Manyara region and Wami-Dakawa in Morogoro region in Tanzania. Venous blood was collected from participants of all age groups, serum prepared from samples and subjected to ELISA tests for RVFV IgG/IgM, DENV IgG/IgM, and CHIKV IgM/IgG. Samples that were positive for IgM ELISA tests were subjected to a quantitative RT PCR for each virus. A structured questionnaire wasused to collect socio-demographic information. Data analysis was performed by using SPSSv22. A total of 191 individuals from both sites participated in the study. Only one individual was CHIKV seropositive in Magugu, but none was seropositive or positive for either RVFV or DENV. Of the 122 individuals from Wami-Dakawa site, 16.39% (n = 20) had recent exposure to RVFV while 9.83% (n = 12) were seropositive for CHIKV. All samples were negative by RVFV and CHIKV qPCR. Neither Infection nor exposure to DENV was observed in participants from both sites. Being more than 5 in a household, having no formal education and having recently travelled to an urban area were risk factors associated with RVFV and CHIKV seropositivity. We report a considerable exposure to RVFV and CHIKV among Wami-Dakawa residents during the dry season and an absence of exposure of the viruses among humans in Magugu site. In both sites, no DENV exposure nor infection was detected.

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