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The small non-coding RNA response to virus infection in the <i>Leishmania</i> vector <i>Lutzomyia longipalpis</i>

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Flávia Viana Ferreira, Eric Roberto Guimarães Rocha Aguiar, Roenick Proveti Olmo, Karla Pollyanna Vieira de Oliveira, Emanuele Guimarães Silva, Maurício Roberto Viana Sant'Anna, Nelder de Figueiredo Gontijo, Erna Geessien Kroon, Jean Luc Imler, João Trindade Marques

Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens.

High incidence of leptospirosis in an observational study of hospital outpatients in Vanuatu highlights the need for improved awareness and diagnostic capacities

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Junior George Pakoa, Marie-Estelle Soupé-Gilbert, Dominique Girault, Dexter Takau, Justina Gaviga, Ann-Claire Gourinat, Arnaud Tarantola, Cyrille Goarant

Background

Estimates of leptospirosis morbidity identified Oceania as the region with highest burden. Besides Australia and New Zealand, Oceania is home of Pacific Island Countries and Territories, most of which are developing countries facing a number of challenges. Their archipelago geography notably affects health infrastructure and access to healthcare. Although human leptospirosis was formerly identified in Vanuatu, there is a lack of knowledge of this disease in the country. We aimed to identify leptospirosis in outpatients visiting the hospital.

Methodology/Principal findings

We conducted a clinical study to investigate leptospirosis as a cause of non-malarial acute febrile illness in Vanuatu. A total 161 outpatients visiting the outpatient clinics at Port Vila Central Hospital for internal medicine were recruited over 20 month. We showed that leptospirosis significantly affects humans in Vanuatu: 12 cases were confirmed by real-time PCR on acute blood samples (n = 5) or by high serology titers evidencing a recent infection (MAT titer ≥800 or ELISA≥18 Units, n = 7). A high rate of positive serology was also evidenced, by MAT (100 Conclusions/Significance

The high numbers of both seropositive patients and acute leptospirosis cases observed in outpatients visiting Port Vila Central Hospital suggest a high exposure to pathogenic Leptospira in the population studied. The MAT serology pointing to serogroup Australis as well as exposure history suggest that livestock animals largely contribute to the burden of human leptospirosis in Vanuatu. The analysis of residential and travel data suggests that the risk might even be higher in other islands of the Vanuatu archipelago. Altogether, our study emphasizes the need to increase awareness and build laboratory capacity to improve the medical care of leptospirosis in Vanuatu.

Diagnostic comparison between FECPAK<sup>G2</sup> and the Kato-Katz method for analyzing soil-transmitted helminth eggs in stool

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Wendelin Moser, Oliver Bärenbold, Greg J. Mirams, Piet Cools, Johnny Vlaminck, Said M. Ali, Shaali M. Ame, Jan Hattendorf, Penelope Vounatsou, Bruno Levecke, Jennifer Keiser

Background

Over one billion people are infected with soil-transmitted helminths (STH), i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura. For estimating drug efficacy and monitoring anthelminthic drug resistance, accurate diagnostic methods are critical. FECPAKG2 is a new remote-diagnostic tool used in veterinary medicine, which produces an image of the stool sample that can be stored on an internet cloud. We compared for the first time FECPAKG2 with the recommended Kato-Katz method.

Methodology/Principal findings

Two stool samples were collected from adolescent participants (age 15–18 years) at baseline and 14 to 21 days after treatment in the framework of a randomized clinical trial on Pemba Island, Tanzania. Stool samples were analyzed with different diagnostic efforts: i) one or ii) two Kato-Katz thick smears from the first sample, iii) two Kato-Katz thick smears from two samples and iv) FECPAKG2 from the first sample. Parameters were calculated based on a hierarchical Bayesian egg count model.Complete data for all diagnostic efforts were available from 615 participants at baseline and 231 hookworm-positive participants at follow-up. At baseline FECPAKG2 revealed a sensitivity of 75.6% (72.0–77.7) for detecting A. lumbricoides, 71.5% (67.4–95.3) for hookworm and 65.8% (64.9–66.2) for T. trichiura, which was significantly lower (all p<0.05) than any of the Kato-Katz methods and highly dependent on infection intensity. Despite that the egg counts based on FECPAKG2 were relatively lower compared to Kato-Katz by a ratio of 0.38 (0.32–0.43) for A. lumbricoides, 0.36 (0.33–0.40) for hookworm and 0.08 (0.07–0.09) for T. trichiura, the egg reduction rates (ERR) were correctly estimated with FECPAKG2.

Conclusions/Significance

The sensitivity to identify any STH infection was considerably lower for FECPAKG2 compared to Kato-Katz. Following rigorous development, FECPAKG2 might be an interesting tool with unique features for epidemiological and clinical studies.

The burden of Neglected Tropical Diseases in Brazil, 1990-2016: A subnational analysis from the Global Burden of Disease Study 2016

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Francisco Rogerlândio Martins-Melo, Mariângela Carneiro, Alberto Novaes Ramos Jr., Jorg Heukelbach, Antonio Luiz Pinho Ribeiro, Guilherme Loureiro Werneck

Background

Neglected Tropical Diseases (NTDs) are important causes of morbidity, disability, and mortality among poor and vulnerable populations in several countries worldwide, including Brazil. We present the burden of NTDs in Brazil from 1990 to 2016 based on findings from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016).

Methodology

We extracted data from GBD 2016 to assess years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for NTDs by sex, age group, causes, and Brazilian states, from 1990 to 2016. We included all NTDs that were part of the priority list of the World Health Organization (WHO) in 2016 and that are endemic/autochthonous in Brazil. YLDs were calculated by multiplying the prevalence of sequelae multiplied by its disability weight. YLLs were estimated by multiplying each death by the reference life expectancy at each age. DALYs were computed as the sum of YLDs and YLLs.

Principal findings

In 2016, there were 475,410 DALYs (95% uncertainty interval [UI]: 337,334–679,482; age-standardized rate of 232.0 DALYs/100,000 population) from the 12 selected NTDs, accounting for 0.8% of national all-cause DALYs. Chagas disease was the leading cause of DALYs among all NTDs, followed by schistosomiasis and dengue. The sex-age-specific NTD burden was higher among males and in the youngest and eldest (children <1 year and those aged ≥70 years). The highest age-standardized DALY rates due to all NTDs combined at the state level were observed in Goiás (614.4 DALYs/100,000), Minas Gerais (433.7 DALYs/100,000), and Distrito Federal (430.0 DALYs/100,000). Between 1990 and 2016, the national age-standardized DALY rates from all NTDs decreased by 45.7%, with different patterns among NTD causes and Brazilian states. Most NTDs decreased in the period, with more pronounced reduction in DALY rates for onchocerciasis, lymphatic filariasis, and rabies. By contrast, age-standardized DALY rates due to dengue, visceral leishmaniasis, and trichuriasis increased substantially. Age-standardized DALY rates decreased for most Brazilian states, increasing only in the states of Amapá, Ceará, Rio Grande do Norte, and Sergipe.

Conclusions/Significance

GBD 2016 findings show that, despite the reduction in disease burden, NTDs are still important and preventable causes of disability and premature death in Brazil. The data call for renewed and comprehensive efforts to control and prevent the NTD burden in Brazil through evidence-informed and efficient and affordable interventions. Multi-sectoral and integrated control and surveillance measures should be prioritized, considering the population groups and geographic areas with the greatest morbidity, disability, and most premature deaths due to NTDs in the country.

Persistence of Yellow fever virus outside the Amazon Basin, causing epidemics in Southeast Brazil, from 2016 to 2018

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Izabela Maurício de Rezende, Lívia Sacchetto, Érica Munhoz de Mello, Pedro Augusto Alves, Felipe Campos de Melo Iani, Talita Émile Ribeiro Adelino, Myrian Morato Duarte, Ana Luísa Furtado Cury, André Felipe Leal Bernardes, Tayrine Araujo Santos, Leonardo Soares Pereira, Maria Rita Teixeira Dutra, Dario Brock Ramalho, Benoit de Thoisy, Erna Geessien Kroon, Giliane de Souza Trindade, Betânia Paiva Drumond

Background

Yellow fever (YF) is endemic in the Brazilian Amazon Basin, and sporadic outbreaks take place outside the endemic area in Brazil. Since 2016, YF epidemics have been occurring in Southeast Brazil, with more than 1,900 human cases and more than 1,600 epizooties of non-human primates (NHPs) reported until April 2018. Previous studies have demonstrated that Yellow fever virus (YFV) causing outbreaks in 2017 formed a monophyletic group.

Methodology/Principal findings

Aiming to decipher the origin of the YFV responsible for the recent epidemics, we obtained nucleotide sequences of YFV detected in humans (n = 6) and NHPs (n = 10) from Minas Gerais state during 2017–2018. Next, we performed evolutionary analyses and discussed the results in the light of epidemiological records (official numbers of YFV cases at each Brazilian Federative unit, reported by the Brazilian Ministry of Health). Nucleotide sequences of YFV from Southeast Brazil from 2016 to 2018 were highly conserved and formed a monophyletic lineage (BR-YFV_2016/18) within the genotype South America I. Different clusters were observed within lineage YFV-BR_2016/18, one containing the majority of isolates (from humans and NHPs), indicating the sylvatic transmission of YFV. We also detected a cluster characterized by two synapomorphies (amino acid substitutions) that contained YFV only associated with NHP what should be further investigated. The topology of lineage BR-YFV_2016/18 was congruent with epidemiological and temporal patterns of the ongoing epidemic. YFV isolates detected in 2016, in São Paulo state were located in the most basal position of the lineage, followed by the isolates from Minas Gerais and Espírito Santo obtained in 2017 and 2018. The most recent common ancestor of the lineage BR-YFV_2016/18 dated to 2015 (95% credible intervals = 2014–2016), in a period that was coincident with the reemergence of YFV in the Midwest region of Brazil.

Conclusions

The results demonstrated a single introduction of YFV in the Southeast region and the silent viral circulation before the onset of the outbreaks in 2016. Evolutionary analyses combined with epidemiological records supported the idea that BR-YFV_2016/18 was probably introduced from the Midwest into the Southeast region, possibly in São Paulo state. The persistence of YFV in the Southeast region, causing epidemics from 2016 to 2018, suggests that this region presents suitable ecological and climatic conditions for YFV maintenance during the epidemic and interepidemic seasons. This fact poses risks for the establishing of YF enzootic cycles and epidemics, outside the Amazon Basin in Brazil. YF surveillance and studies of viral dynamics deserve particular attention, especially in Midwest, Southeast and neighbor regions which are the main areas historically associated with YF outbreaks outside the Amazon Basin. YFV persistence in Southeast Brazil should be carefully considered in the context of public health, especially for public health decision-makers and researchers.

Improving early epidemiological assessment of emerging <i>Aedes</i>-transmitted epidemics using historical data

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Julien Riou, Chiara Poletto, Pierre-Yves Boëlle

Model-based epidemiological assessment is useful to support decision-making at the beginning of an emerging Aedes-transmitted outbreak. However, early forecasts are generally unreliable as little information is available in the first few incidence data points. Here, we show how past Aedes-transmitted epidemics help improve these predictions. The approach was applied to the 2015–2017 Zika virus epidemics in three islands of the French West Indies, with historical data including other Aedes-transmitted diseases (Chikungunya and Zika) in the same and other locations. Hierarchical models were used to build informative a priori distributions on the reproduction ratio and the reporting rates. The accuracy and sharpness of forecasts improved substantially when these a priori distributions were used in models for prediction. For example, early forecasts of final epidemic size obtained without historical information were 3.3 times too high on average (range: 0.2 to 5.8) with respect to the eventual size, but were far closer (1.1 times the real value on average, range: 0.4 to 1.5) using information on past CHIKV epidemics in the same places. Likewise, the 97.5% upper bound for maximal incidence was 15.3 times (range: 2.0 to 63.1) the actual peak incidence, and became much sharper at 2.4 times (range: 1.3 to 3.9) the actual peak incidence with informative a priori distributions. Improvements were more limited for the date of peak incidence and the total duration of the epidemic. The framework can adapt to all forecasting models at the early stages of emerging Aedes-transmitted outbreaks.

Improving spatial prediction of <i>Schistosoma haematobium</i> prevalence in southern Ghana through new remote sensors and local water access profiles

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Alexandra V. Kulinkina, Yvonne Walz, Magaly Koch, Nana-Kwadwo Biritwum, Jürg Utzinger, Elena N. Naumova

Background

Schistosomiasis is a water-related neglected tropical disease. In many endemic low- and middle-income countries, insufficient surveillance and reporting lead to poor characterization of the demographic and geographic distribution of schistosomiasis cases. Hence, modeling is relied upon to predict areas of high transmission and to inform control strategies. We hypothesized that utilizing remotely sensed (RS) environmental data in combination with water, sanitation, and hygiene (WASH) variables could improve on the current predictive modeling approaches.

Methodology

Schistosoma haematobium prevalence data, collected from 73 rural Ghanaian schools, were used in a random forest model to investigate the predictive capacity of 15 environmental variables derived from RS data (Landsat 8, Sentinel-2, and Global Digital Elevation Model) with fine spatial resolution (10–30 m). Five methods of variable extraction were tested to determine the spatial linkage between school-based prevalence and the environmental conditions of potential transmission sites, including applying the models to known human water contact locations. Lastly, measures of local water access and groundwater quality were incorporated into RS-based models to assess the relative importance of environmental and WASH variables.

Principal findings

Predictive models based on environmental characterization of specific locations where people contact surface water bodies offered some improvement as compared to the traditional approach based on environmental characterization of locations where prevalence is measured. A water index (MNDWI) and topographic variables (elevation and slope) were important environmental risk factors, while overall, groundwater iron concentration predominated in the combined model that included WASH variables.

Conclusions/Significance

The study helps to understand localized drivers of schistosomiasis transmission. Specifically, unsatisfactory water quality in boreholes perpetuates reliance of surface water bodies, indirectly increasing schistosomiasis risk and resulting in rapid reinfection (up to 40% prevalence six months following preventive chemotherapy). Considering WASH-related risk factors in schistosomiasis prediction can help shift the focus of control strategies from treating symptoms to reducing exposure.

Molecular characterisation of <i>Vibrio cholera</i> responsible for cholera epidemics in Uganda by PCR, MLVA and WGS

PLoS Neglected Tropical Diseases News - 4 June 2018 - 9:00pm

by Godfrey Bwire, David A. Sack, Mathieu Almeida, Shan Li, Joseph B. Voeglein, Amanda Kay Debes, Atek Kagirita, Ambrose Wabwire Buyinza, Christopher Garimoi Orach, O. Colin Stine

Background

For almost 50 years sub-Saharan Africa, including Uganda, has experienced several outbreaks due to Vibrio cholerae. Our aim was to determine the genetic relatedness and spread of strains responsible for cholera outbreaks in Uganda.

Methodology/Principal findings

Sixty-three V. cholerae isolates collected from outbreaks in Uganda between 2014 and 2016 were tested using multiplex polymerase chain reaction (PCR), multi-locus variable number of tandem repeat analysis (MLVA) and whole genome sequencing (WGS). Three closely related MLVA clonal complexes (CC) were identified: CC1, 32% (20/63); CC2, 40% (25/63) and CC3, 28% (18/63). Each CC contained isolates from a different WGS clade. These clades were contained in the third wave of the 7th cholera pandemic strain, two clades were contained in the transmission event (T)10 lineage and other in T13. Analysing the dates and genetic relatedness revealed the V. cholerae genetic lineages spread between districts within Uganda and across national borders.

Conclusion

The V. cholerae strains showed local and regional transmission within Uganda and the East African region. To prevent, control and eliminate cholera, these countries should implement strong cross-border collaboration and regional coordination of preventive activities.

Transrenal DNA-based diagnosis of <i>Strongyloides stercoralis</i> (Grassi, 1879) infection: Bayesian latent class modeling of test accuracy

PLoS Neglected Tropical Diseases News - 1 June 2018 - 9:00pm

by Alejandro J. Krolewiecki, Artemis Koukounari, Miryam Romano, Nicolas N. Caro, Alan L. Scott, Pedro Fleitas, Rubin Cimino, Clive J. Shiff

For epidemiological work with soil transmitted helminths the recommended diagnostic approaches are to examine fecal samples for microscopic evidence of the parasite. In addition to several logistical and processing issues, traditional diagnostic approaches have been shown to lack the sensitivity required to reliably identify patients harboring low-level infections such as those associated with effective mass drug intervention programs. In this context, there is a need to rethink the approaches used for helminth diagnostics. Serological methods are now in use, however these tests are indirect and depend on individual immune responses, exposure patterns and the nature of the antigen. However, it has been demonstrated that cell-free DNA from pathogens and cancers can be readily detected in patient’s urine which can be collected in the field, filtered in situ and processed later for analysis. In the work presented here, we employ three diagnostic procedures—stool examination, serology (NIE-ELISA) and PCR-based amplification of parasite transrenal DNA from urine–to determine their relative utility in the diagnosis of S. stercoralis infections from 359 field samples from an endemic area of Argentina. Bayesian Latent Class analysis was used to assess the relative performance of the three diagnostic procedures. The results underscore the low sensitivity of stool examination and support the idea that the use of serology combined with parasite transrenal DNA detection may be a useful strategy for sensitive and specific detection of low-level strongyloidiasis.

A FRET flow cytometry method for monitoring cytosolic and glycosomal glucose in living kinetoplastid parasites

PLoS Neglected Tropical Diseases News - 31 May 2018 - 9:00pm

by Charles M. Voyton, Yijian Qiu, Meredith T. Morris, P. Christine Ackroyd, Jimmy Suryadi, Logan Crowe, James C. Morris, Kenneth A. Christensen

The bloodstream lifecycle stage of the kinetoplastid parasite Trypanosoma brucei relies solely on glucose metabolism for ATP production, which occurs in peroxisome-like organelles (glycosomes). Many studies have been conducted on glucose uptake and metabolism, but none thus far have been able to monitor changes in cellular and organellar glucose concentration in live parasites. We have developed a non-destructive technique for monitoring changes in cytosolic and glycosomal glucose levels in T. brucei using a fluorescent protein biosensor (FLII12Pglu-700μδ6) in combination with flow cytometry. T. brucei parasites harboring the biosensor allowed for observation of cytosolic glucose levels. Appending a type 1 peroxisomal targeting sequence caused biosensors to localize to glycosomes, which enabled observation of glycosomal glucose levels. Using this approach, we investigated cytosolic and glycosomal glucose levels in response to changes in external glucose or 2-deoxyglucose concentration. These data show that procyclic form and bloodstream form parasites maintain different glucose concentrations in their cytosol and glycosomes. In procyclic form parasites, the cytosol and glycosomes maintain indistinguishable glucose levels (3.4 ± 0.4mM and 3.4 ± 0.5mM glucose respectively) at a 6.25mM external glucose concentration. In contrast, bloodstream form parasites maintain glycosomal glucose levels that are ~1.8-fold higher than the surrounding cytosol, equating to 1.9 ± 0.6mM in cytosol and 3.5 ± 0.5mM in glycosomes. While the mechanisms of glucose transport operating in the glycosomes of bloodstream form T. brucei remain unresolved, the methods described here will provide a means to begin to dissect the cellular machinery required for subcellular distribution of this critical hexose.

Zika virus infection in Nicaraguan households

PLoS Neglected Tropical Diseases News - 31 May 2018 - 9:00pm

by Raquel Burger-Calderon, Karla Gonzalez, Sergio Ojeda, José Victor Zambrana, Nery Sanchez, Cristhiam Cerpas Cruz, Harold Suazo Laguna, Fausto Bustos, Miguel Plazaola, Brenda Lopez Mercado, Douglas Elizondo, Sonia Arguello, Jairo Carey Monterrey, Andrea Nuñez, Josefina Coloma, Jesse J. Waggoner, Aubree Gordon, Guillermina Kuan, Angel Balmaseda, Eva Harris

Zika virus (ZIKV) infection recently caused major epidemics in the Americas and is linked to congenital birth defects and Guillain-Barré Syndrome. A pilot study of ZIKV infection in Nicaraguan households was conducted from August 31 to October 21, 2016, in Managua, Nicaragua. We enrolled 33 laboratory-confirmed Zika index cases and their household members (109 contacts) and followed them on days 3–4, 6–7, 9–10, and 21, collecting serum/plasma, urine, and saliva specimens along with clinical, demographic, and socio-economic status information. Collected samples were processed by rRT-PCR to determine viral load (VL) and duration of detectable ZIKV RNA in human bodily fluids. At enrollment, 11 (10%) contacts were ZIKV rRT-PCR-positive and 23 (21%) were positive by IgM antibodies; 3 incident cases were detected during the study period. Twenty of 33 (61%) index households had contacts with ZIKV infection, with an average of 1.9 (range 1–6) positive contacts per household, and in 60% of these households, ≥50% of the members were positive for ZIKV infection. Analysis of clinical information allowed us to estimate the symptomatic to asymptomatic (S:A) ratio of 14:23 (1:1.6) among the contacts, finding 62% of the infections to be asymptomatic. The maximum number of days during which ZIKV RNA was detected was 7 days post-symptom onset in saliva and serum/plasma and 22 days in urine. Overall, VL levels in serum/plasma, saliva, and urine specimens were comparable, with means of 5.6, 5.3 and 4.5 log10 copies/ml respectively, with serum attaining the highest VL peak at 8.1 log10 copies/ml. Detecting ZIKV RNA in saliva over a similar time-period and level as in serum/plasma indicates that saliva could potentially serve as a more accessible diagnostic sample. Finding the majority of infections to be asymptomatic emphasizes the importance of silent ZIKV transmission and helps inform public health interventions in the region and globally.

Detection and phylogenetic characterization of arbovirus dual-infections among persons during a chikungunya fever outbreak, Haiti 2014

PLoS Neglected Tropical Diseases News - 31 May 2018 - 9:00pm

by Sarah K. White, Carla Mavian, Maha A. Elbadry, Valery Madsen Beau De Rochars, Taylor Paisie, Taina Telisma, Marco Salemi, John A. Lednicky, J. Glenn Morris Jr.

In the context of recent arbovirus epidemics, questions about the frequency of simultaneous infection of patients with different arbovirus species have been raised. In 2014, a major Chikungunya virus (CHIKV) epidemic impacted the Caribbean and South America. As part of ongoing screening of schoolchildren presenting with acute undifferentiated febrile illness in rural Haiti, we used RT-PCR to identify CHIKV infections in 82 of 100 children with this diagnosis during May—August 2014. Among these, eight were infected with a second arbovirus: six with Zika virus (ZIKV), one with Dengue virus serotype 2, and one with Mayaro virus (MAYV). These dual infections were only detected following culture of the specimen, suggesting low viral loads of the co-infecting species. Phylogenetic analyses indicated that the ZIKV and MAYV strains differ from those detected later in 2014 and 2015, respectively. Moreover, CHIKV and ZIKV strains from co-infected patients clustered monophyletically in their respective phylogeny, and clock calibration traced back the common ancestor of each clade to an overlapping timeframe of introduction of these arboviruses onto the island.

Deworming in pre-school age children: A global empirical analysis of health outcomes

PLoS Neglected Tropical Diseases News - 31 May 2018 - 9:00pm

by Nathan C. Lo, Jedidiah Snyder, David G. Addiss, Sam Heft-Neal, Jason R. Andrews, Eran Bendavid

Background

There is debate over the effectiveness of deworming children against soil-transmitted helminthiasis (STH) to improve health outcomes, and current evidence may be limited in study design and generalizability. However, programmatic deworming continues throughout low and middle-income countries.

Methodology and principal findings

We performed an empirical evaluation of the relationship between deworming in pre-school age children (ages 1–4 years) within the previous 6 months, as proxy-reported by the mother, and health outcomes of weight, height, and hemoglobin. We used nationally representative cross-sectional data from 45 countries using the Demographic and Health Surveys (DHS) during the period 2005–2016. We used logistic regression with coarsened exact matching, fixed effects for survey and year, and person-level covariates. We included data on 325,115 children in 45 STH-endemic countries from 66 DHS surveys. Globally in STH-endemic countries, children who received deworming treatment were less likely to be stunted (1.2 percentage point decline from mean of 36%; 95% CI [-1.9, -0.5%]; p<0.001), but we did not detect consistent associations between deworming and anemia or weight. In sub-Saharan Africa, we found that children who received deworming treatment were less likely to be stunted (1.1 percentage point decline from mean of 36%; 95% CI [-2.1, -0.2%]; p = 0.01) and less likely to have anemia (1.8 percentage point decline from mean of 58%; 95% CI [-2.8, -0.7%]; p<0.001), but we did not detect consistent associations between deworming and weight. These findings were robust across multiple statistical models, and we did not find consistently measurable associations with data from non-endemic settings.

Conclusions and significance

Among pre-school age children, we detected a robust and consistent association between deworming and reduced stunting, with additional evidence for reduced anemia in sub-Saharan Africa. We did not find a consistent relationship between deworming and improved weight. This global empirical analysis provides evidence to support the deworming of pre-school age children.

Causes of acute undifferentiated fever and the utility of biomarkers in Chiangrai, northern Thailand

PLoS Neglected Tropical Diseases News - 31 May 2018 - 9:00pm

by Tri Wangrangsimakul, Thomas Althaus, Mavuto Mukaka, Pacharee Kantipong, Vanaporn Wuthiekanun, Wirongrong Chierakul, Stuart D. Blacksell, Nicholas P. Day, Achara Laongnualpanich, Daniel H. Paris

Background

Tropical infectious diseases like dengue, scrub typhus, murine typhus, leptospirosis, and enteric fever continue to contribute substantially to the febrile disease burden throughout Southeast Asia while malaria is declining. Recently, there has been increasing focus on biomarkers (i.e. C-reactive protein (CRP) and procalcitonin) in delineating bacterial from viral infections.

Methodology/Principal findings

A prospective observational study was performed to investigate the causes of acute undifferentiated fever (AUF) in adults admitted to Chiangrai Prachanukroh hospital, northern Thailand, which included an evaluation of CRP and procalcitonin as diagnostic tools. In total, 200 patients with AUF were recruited. Scrub typhus was the leading bacterial cause of AUF (45/200, 22.5%) followed by leptospirosis (15/200, 7.5%) and murine typhus (7/200, 3.5%), while dengue was the leading viral cause (23/200, 11.5%). Bloodstream infections contributed to 7/200 (3.5%) of the study cohort. There were 9 deaths during this study (4.5%): 3 cases of scrub typhus, 2 with septicaemia (Talaromyces marneffei and Haemophilus influenzae), and 4 of unknown aetiologies. Rickettsioses, leptospirosis and culture-attributed bacterial infections, received a combination of 3rd generation cephalosporin plus a rickettsia-active drug in 53%, 73% and 67% of cases, respectively. Low CRP and white blood count were significant predictors of a viral infection (mainly dengue) while the presence of an eschar and elevated aspartate aminotransferase and alkaline phosphatase were important predictors of scrub typhus.

Interpretation

Scrub typhus and dengue are the leading causes of AUF in Chiangrai, Thailand. Eschar, white blood count and CRP were beneficial in differentiating between bacterial and viral infections in this study. CRP outperformed procalcitonin although cut-offs for positivity require further assessment. The study provides evidence that accurate, pathogen-specific rapid diagnostic tests coupled with biomarker point-of-care tests such as CRP can inform the correct use of antibiotics and improve antimicrobial stewardship in this setting.

A serologic study of dengue in northwest Ethiopia: Suggesting preventive and control measures

PLoS Neglected Tropical Diseases News - 31 May 2018 - 9:00pm

by Getachew Ferede, Moges Tiruneh, Ebba Abate, Yitayih Wondimeneh, Demekech Damtie, Endalamaw Gadisa, Rawleigh Howe, Abraham Aseffa, Belay Tessema

Background

Dengue is one of the most serious and rapidly spreading arboviral diseases in the world. Despite many acute febrile illnesses in Ethiopia, the burden of illness due to dengue in the country is largely unknown. Thus, the present study aimed to provide the first baseline data on seroprevalence and associated risk factors of dengue virus (DENV) infection in the country.

Methods

A cross-sectional study of febrile patients who were visiting Metema and Humera hospitals in Northwest Ethiopia from March 2016 to May 2017 was conducted. Blood samples were collected from each participant and serum samples were separated and tested for IgM and IgG antibodies against DENV infection by enzyme-linked immunosorbent assay (ELISA). Risk factors associated with the prevalence of anti-DENV antibodies were tested using logistic regression analysis.

Results

Of the 600 samples tested, the overall seroprevalence against DENV infection was 33.3%, while the seroprevalence by the study area was 40% in Metema and 27.5% in Humera. The overall prevalence of IgM and IgG antibodies against DENV infection was 19% and 21% respectively. Of these, 6.7% were positive for both IgM and IgG antibodies. Residence and occupational status were significantly associated with the prevalence of anti-DENV IgM seropositivity and anti-DENV IgM-/G+serostatus. The seasonal variation was significantly associated with the prevalence of anti-DENV IgM but not with anti-DENV IgM-/G+serostatus. The prevalence of anti-DENV IgM-/G+serostatus was significantly higher in Metema than Humera. High prevalence of anti-DENV IgM seropositivity was found in the summer and spring, with a peak in the month of August. The presence of uncovered water either indoor or outdoor and lack of mosquito net use was identified as risk factors for DENV infection.

Conclusions

These findings provide the preliminary data on seroprevalence and associated risk factors of DENV infection in the country. The presence of antibodies against DENV infection indicates dengue as one of the causes of undifferentiated febrile illnesses in the study areas. This suggests that prevention and control measures should be designed considering the risk factors identified by this study. Furthermore, we recommend a large-scale study to include DENV infection in the differential diagnosis of all febrile illnesses in Ethiopia.

Scabies and impetigo in Timor-Leste: A school screening study in two districts

PLoS Neglected Tropical Diseases News - 31 May 2018 - 9:00pm

by Laura M. Korte, Asha C. Bowen, Anthony D. K. Draper, Kim Davis, Annette Steel, Ines Teodora, Ivonia Mascarenhas, Benjamin Dingle, Joshua R. Francis

Introduction

Scabies and impetigo are common and important skin conditions which are often neglected in developing countries. Limited data have been published on the prevalence of scabies and impetigo in Timor-Leste. Sequelae including cellulitis, bacteraemia, nephritis, acute rheumatic fever and rheumatic heart disease contribute significantly to the burden of disease.

Methods

School students were recruited from schools in Dili (urban) and Ermera (rural) in Timor-Leste for an epidemiological study in October 2016. A standard questionnaire was used to record demographics, anthropometry and skin examination results. Impetigo and scabies were diagnosed based on clinical examination of exposed surfaces, and clinical photographs were reviewed for correlation by an infectious diseases paediatrician. Prevalence of scabies and impetigo were calculated and binary risk factor associations were described using relative risks and 95% confidence intervals. Adjusted odds ratios were calculated using logistic regression multivariate analysis. Continuous variables were analysed for associations using the Mann-Whitney Rank Sum test.

Results

The study enrolled 1396 students; median age 11 years (interquartile range (IQR) 9–15). The prevalence of scabies was 22.4% (95% CI 20.2–24.7%) and active impetigo 9.7% (95% CI 8.3–11.4%); 68.2% of students had evidence of either active or healed impetigo. Students in Ermera were more likely than those in Dili to have scabies (prevalence 32.0% vs 5.2%, aOR 8.1 (95% CI 5.2–12.4), p<0.01). There was no difference in the prevalence of active impetigo between urban and rural sites. More than a third of participants were moderately or severely underweight. Stunting was markedly more common in the rural district of Ermera.

Conclusion

Scabies and impetigo are common in Timor-Leste, with very high prevalence of scabies in the rural district of Ermera. Improvements in prevention and treatment are needed, with prioritised activities in the rural areas where prevalence is highest.

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