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Rabies is a lethal zoonotic encephalomyelitis that causes an estimated 59,000 human deaths yearly worldwide. Although developing countries of Asia and Africa bear the heaviest burden, surveillance and disease detection in these countries is often hampered by the absence of local laboratories able to diagnose rabies and/or the difficulties of sample shipment from low-access areas to national reference laboratories. Filter papers offer a convenient cost-effective alternative for the sampling, shipment, and storage of biological materials for the diagnosis of many pathogens including rabies virus, yet the properties of diagnostic tests using this support have not been evaluated thoroughly. Sensitivity and specificity of molecular diagnosis of rabies infection using a reverse transcription followed by a hemi-nested polymerase chain reaction (RT-hn-PCR) either directly on brain tissue or using brain tissue dried on filter paper were assessed on 113 suspected field animal samples in comparison to the direct fluorescent antibody test (FAT) recommended by the World Health Organization as one of the reference tests for rabies diagnosis. Impact of the duration of the storage was also evaluated. The sensitivity and the specificity of RT-hn-PCR i) on brain tissue were 96.6% (95% CI: [88.1-99.6]) and 92.7% (95% CI: [82.4-98.0]) respectively and ii) on brain tissue dried on filter paper 100% (95% CI: [93.8-100.0]) and 90.9% (95% CI: [80.0-97.0]) respectively. No loss of sensitivity of RT-hn-PCR on samples of brain tissue dried on filter paper left 7 days at ambient temperature was detected indicating that this method would enable analyzing impregnated filter papers sent to the national reference laboratory at ambient temperature within a 1-week shipment time. It could therefore be an effective alternative to facilitate storage and shipment of samples from low-access areas to enhance and expand rabies surveillance., Competing Interests: The authors have declared that no competing interests exist.

Background: Up to 1.45 billion people currently suffer from soil transmitted helminth infection, with the largest burden occurring in Africa and Asia. Safe and cost effective deworming treatment exists, but there is a debate about mass distribution of this treatment in high prevalence settings. While the World Health Organization recommends mass administration of anthelmintic drugs for preschool and school-aged children in high (>20%) prevalence settings, and several long run follow up studies of an influential trial have suggested large benefits that persist over time, recent systematic reviews have called this recommendation into question. Methods and findings: This paper analyzes the long-term impact of a cluster-randomized trial in eastern Uganda that provided mass deworming treatment to preschool aged children from 2000 to 2003 on the numeracy and literacy skills of children and young adults living in those villages in 2010-2015. This study uses numeracy and literacy data collected seven to twelve years after the end of the deworming trial in a randomly selected subset of communities from the original trial, by an education-focused survey that had no relationship to the deworming study. Building on an earlier working paper which used data from 2010 and 2011 survey rounds, this paper uses an additional four years of numeracy and literacy data (2012, 2013, 2014, and 2015). Aggregating data from all survey rounds, the difference between numeracy scores in treatment versus control communities is 0.07 standard deviations (SD) (95% CI -0.10, 0.24, p = 0.40), the difference in literacy scores is 0.05 SD (95% CI -0.16, 0.27, p = 0.62), and the difference in total scores is 0.07 SD (95% CI -0.11, 0.25, p = 0.44). There are significant differences in program impact by gender, with numeracy and literacy differentially positively affected for girls, and by age, with treatment effects larger for the primary school aged subsample. There are also significant treatment interactions for those living in households with more treatment-eligible children. There is no evidence of differential treatment effects on age at program eligibility or number of years of program eligibility. Conclusions: Mass deworming of preschool aged children in high prevalence communities in Uganda resulted in no statistically significant gains in numeracy or literacy 7-12 years after program completion. Point estimates were positive but imprecise; the study lacked sufficient power to rule out substantial positive effects or more modest negative effects. However, there is suggestive evidence that deworming was relatively more beneficial for girls, primary school aged children, and children living in households with other treated children. Research approval: As this analysis was conducted on secondary data which is publicly available, no research approval was sought or received. All individual records were anonymized by the data provider prior to public release. [ABSTRACT FROM AUTHOR]

Russell's vipers (RVs) envenoming is an important public health issue in South-East Asia. Disseminated intravascular coagulopathy, systemic bleeding, hemolysis, and acute renal injury are obvious problems that develop in most cases, and neuromuscular junction blocks are an additional problem caused by western RV snakebite. The complex presentations usually are an obstacle to early diagnosis and antivenom administration. Here, we tried to produce highly specific antibodies in goose yolks for use in a paper-based microfluidic diagnostic kit, immunochromatographic test of viper (ICT-Viper), to distinguish RVs from other vipers and even cobra snakebite in Asia. We used indirect ELISA to monitor specific goose IgY production and western blotting to illustrate the interaction of avian or mammal antibody with venom proteins. The ICT-Viper was tested not only in prepared samples but also in stored patient serum to demonstrate its preliminary efficacy. The results revealed that specific anti-Daboia russelii IgY could be raised in goose eggs effectively without inducing adverse effects. When it was collocated with horse anti-Daboia siamensis antibody, which broadly reacted with most of the venom proteins of both types of Russell's viper, the false cross-reactivity was reduced, and the test showed good performance. The limit of detection was reduced to 10 ng/ml in vitro, and the test showed good detection ability in clinical snake envenoming case samples. The ICT-Viper performed well and could be combined with a cobra venom detection kit (ICT-Cobra) to create a multiple detection strip (ICT-VC), which broadens its applications while maintaining its detection ability for snake envenomation identification. Nonetheless, the use of the ICT-Viper in the South-East Asia region is pending additional laboratory and field investigations and regional collaboration. We believe that the development of this practical diagnostic tool marks the beginning of positive efforts to face the global snakebite issue. Author summary: For a long time, many scientists have made efforts to develop more effective antivenoms or to expand the limits of existing antivenoms. Such endeavors are challenging but worth the effort in the long run. However, to use precious antivenom more effectively, a snake species discrimination tool might be helpful for treatment by ensuring accurate antivenom usage and dosage. In this study, we revealed that avian IgY might be an economical alternative for collocation with the equine F(ab')2 fragment in the development of a diagnostic device with improved performance. Only a few avian eggs (about 10–15) would be necessary to produce 10,000 kits. Immunochromatographic test (ICT) is a simple, easy, fast, and low-cost point-of-care lateral flow assay device, and especially adapted to perform in resource-deficient areas. Such an antibody collocation strategy might be beneficial to overcome the urgent need for snakebite diagnosis as soon as possible. More cooperative investigations across Asia continent might be initiated in the future to face the challenge of snakebites together. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is a severe form of the leishmaniasis-disease complex. Its importance to public health relies on its high fatality rate in non-treated cases, the socio-economic impact related to its morbidity, and its endemicity on different continents. The estimated burden of disease of VL varies from 1,969,000 to 2,357,000 Disability Adjusted Life Years (DALYs). VL is classified as a Neglected Tropical Disease (NTD), and is strongly related to poverty and its consequences. Visceral leishmaniasis calls for the development of cost-effective technologies for diagnosis and treatment. Objective: The main objective of this study was to identify, describe, classify and analyze the scientific health economic evidence of VL-related technologies. Methods: A web search of combinations of free text and Mesh terms related to the economic evaluation of visceral leishmaniasis was conducted on scientific publication databases (Web of Science, Scopus, Medline via the Pubmed and Lilacs). A manual search of references lists of articles previously identified by the authors was also included. Articles written in English, Portuguese, Spanish or French were considered suitable for inclusion. Articles that matched the inclusion criteria were screened by at least two researchers, who extracted information regarding the epidemiologic scenario and methodological issues on a standardized form. Results: The initial search retrieved 107 articles, whose abstracts were inspected according to the inclusion criteria leading to a first selection of 49 (46%) articles. After the elimination of duplicates, the list was reduced to 21 (20%) articles. After careful reading and application of exclusion criteria, 14 papers were eligible according to the description, classification and analysis process proposed by the study. When classified by type of economic evaluation, articles were 7 (50%) cost-effectiveness, 5 (36%) cost-minimization, 1(7%) cost-benefit, and 1(7%) budget impact. When classified by methodology, studies were mainly nested to clinical-trials ("piggy back") 8(57%). Discount rates for outcomes and costs were present in 3 (43%) of the cost-effectiveness studies, and according to WHO's recommendations, the discount rate of 3% was used in all studies. Conclusions: This article showed that health economic evaluations on visceral leishmaniasis used a wide range of technologies and methods. Nevertheless it is important to point out the geographic concentration of studies, which makes their transferability uncertain to different epidemiological scenarios, especially those concerning visceral leishmaniasis caused by Leishmania infantum. Author Summary: Visceral leishmaniasis (VL), also known as kala azar, is a neglected tropical disease caused by parasitic protozoa of the genus Leishmania. VL is related to poverty and its consequences, which leads to its status of neglected disease. For that reason, cost-effective forms of diagnoses and treatment are very important and still needed. This research aimed at a better understanding of the publications about the technologies currently available, from the standpoint of their economic value. For that purpose, we conducted a systematic review of the literature in order to identify the papers that conducted economic evaluations of technologies used in VL. We initially retrieved 107 articles, which were inspected according to specific guidelines for systematic reviews. After that process, 14 articles matched the inclusion criteria in our review. We classified those studies according to the type of economic evaluation they made, and the methodology used in each one. We found evaluations about a variety of technologies, but the studies were geographically concentrated in Asia, more specifically in India. This concentration is not good because the disease also affects other continents and it is not possible to transfer the economic evaluation from one country or epidemiologic scenario to another. [ABSTRACT FROM AUTHOR]

Although Japanese encephalitis virus genotype Ib (JEV GIb) has replaced JEV GIII as the dominant genotype in endemic areas of Asia, no JEV GIb has been isolated from JE cases and natural mosquitoes at the same time in an outbreak of JE. In this study, we conducted virological and molecular biological laboratory tests on JE case samples (serum/cerebrospinal fluid) and locally collected mosquito samples from the 2018 JE outbreak in Ningxia, China. The result of JEV IgM antibody detection showed that 96% (67/70) of the suspected cases were laboratory-confirmed JE cases. Of the mosquitoes collected from local environments, 70% (17400/24900) were Culex tritaeniorhynchus of which 4.6% (16 /348 of the pools tested) were positive for JEV, other mosquitoes were negative. JEVs isolated from both the human cases and C. tritaeniorhynchus specimens belong to JEV GIb and are in the same evolutionary clade according to molecular evolution analyses. JEV GIb was detected simultaneously from specimens of JE cases and mosquito samples collected in nature in this study, suggesting that the JE outbreak that occurred in Ningxia in 2018 was due to infection of JEV GIb. Author summary: Japanese encephalitis virus (JEV) is recognized as an important encephalitis pathogen all over the world. Its genotype is divided into GI-V. In recent years, JEV GIb (a temperate genotype) has gradually replaced GIII as the prevalent strain in JE endemic areas. Although JEV GIb originated from tropical Asia along with JEV GIa, it has rapidly spread for its advantages in wintering and infecting vectors. Although there have been epidemics caused by JEV GI and GIII, there have been no reports of a JE outbreak caused by JEV GIb alone in northeastern Asia. However, a JE outbreak occurred in the Ningxia Hui Autonomous Region in northern China in summer 2018 which was the first outbreak in Ningxia in recent decades. This paper presents a series of laboratory and field studies of this outbreak. The strain isolated from JE cases as well as JEV detected in Culex tritaeniorhynchus collected from local areas in nature all belonged to JEV GIb and were in the same evolutionary clade. This is the first report of a JE outbreak caused by JEV GIb infection in northeastern Asia (latitude 35 ° 14'– 39 ° 23' N, longitude 104 ° 17'– 107 ° 39' E), which used to be a low endemic area of JEV GIII. [ABSTRACT FROM AUTHOR]

Targeted environmental and ecosystem management remain crucial in control of dengue. However, providing detailed environmental information on a large scale to effectively target dengue control efforts remains a challenge. An important piece of such information is the extent of the presence of potential dengue vector breeding sites, which consist primarily of open containers such as ceramic jars, buckets, old tires, and flowerpots. In this paper we present the design and implementation of a pipeline to detect outdoor open containers which constitute potential dengue vector breeding sites from geotagged images and to create highly detailed container density maps at unprecedented scale. We implement the approach using Google Street View images which have the advantage of broad coverage and of often being two to three years old which allows correlation analyses of container counts against historical data from manual surveys. Containers comprising eight of the most common breeding sites are detected in the images using convolutional neural network transfer learning. Over a test set of images the object recognition algorithm has an accuracy of 0.91 in terms of F-score. Container density counts are generated and displayed on a decision support dashboard. Analyses of the approach are carried out over three provinces in Thailand. The container counts obtained agree well with container counts from available manual surveys. Multi-variate linear regression relating densities of the eight container types to larval survey data shows good prediction of larval index values with an R-squared of 0.674. To delineate conditions under which the container density counts are indicative of larval counts, a number of factors affecting correlation with larval survey data are analyzed. We conclude that creation of container density maps from geotagged images is a promising approach to providing detailed risk maps at large scale. [ABSTRACT FROM AUTHOR]

Background: The Bangladesh Lymphatic Filariasis (LF) Elimination Programme has made significant progress in interrupting transmission through mass drug administration (MDA) and has now focussed its efforts on scaling up managing morbidity and preventing disability (MMDP) activities to deliver the minimum package of care to people affected by LF clinical conditions. This paper highlights the Bangladesh LF Programme’s success in conducting a large-scale cross-sectional survey to determine the number of people affected by lymphoedema and hydrocoele, which enabled clinical risk maps to be developed for targeted interventions across the 34 endemic districts (19 high endemic; 15 low endemic). Methodology/Principal findings: In the 19 high endemic districts, 8,145 community clinic staff were trained to identify and report patients in their catchment area. In the 15 low endemic districts, a team of 10 trained field assistants conducted active case finding with cases reported via a SMS mHealth tool. Disease burden and prevalence maps were developed, with morbidity hotspots identified at sub-district level based on a combination of the highest prevalence rates per 100,000 and case-density rates per square kilometre (km2). The relationship between morbidity and baseline microfilaria (mf) prevalence was also examined. In total 43,678 cases were identified in the 19 high endemic districts; 30,616 limb lymphoedema (70.1%; female 55.3%), 12,824 hydrocoele (29.4%), and 238 breast/female genital swelling (0.5%). Rangpur Division reported the highest cases numbers and prevalence of lymphoedema (26,781 cases, 195 per 100,000) and hydrocoele (11661 cases, 169.6 per 100,000), with lymphoedema predominately affecting females (n = 21,652). Rangpur and Lalmonirhat Districts reported the highest case numbers (n = 11,199), and prevalence (569 per 100,000) respectively, with five overlapping lymphoedema and hydrocoele sub-district hotspots. In the 15 low endemic districts, 732 cases were identified; 661 lymphoedema (90.2%; female 39.6%), 56 hydrocoele (7.8%), and 15 both conditions (2.0%). Spearman’s correlation analysis found morbidity and mf prevalence significantly positively correlated (r = 0.904; p<0.01). Conclusions/Significance: The Bangladesh LF Programme has developed one of the largest, most comprehensive country databases on LF clinical conditions in the world. It provides an essential database for health workers to identify local morbidity hotspots, deliver the minimum package of care, and address the dossier elimination requirements. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic Leishmania donovani infections outnumber clinical presentations, however the predictors for development of active disease are not well known. We aimed to identify serological, immunological and genetic markers for progression from L. donovani infection to clinical Visceral Leishmaniasis (VL). Methods: We enrolled all residents >2 years of age in 27 VL endemic villages in Bihar (India). Blood samples collected on filter paper on two occasions 6–12 months apart, were tested for antibodies against L. donovani with rK39-ELISA and DAT. Sero converters, (negative for both tests in the first round but positive on either of the two during the second round) and controls (negative on both tests on both occasions) were followed for three years. At the start of follow-up venous blood was collected for the following tests: DAT, rK39- ELISA, Quantiferon assay, SNP/HLA genotyping and L.donovani specific quantitative PCR. Results: Among 1,606 subjects enrolled,17 (8/476 seroconverters and 9/1,130 controls) developed VL (OR 3.1; 95% CI 1.1–8.3). High DAT and rK39 ELISA antibody titers as well as positive qPCR were strongly and significantly associated with progression from seroconversion to VL with odds ratios of 19.1, 30.3 and 20.9 respectively. Most VL cases arose early (median 5 months) during follow-up. Conclusion: We confirmed the strong association between high DAT and/or rK39 titers and progression to disease among asymptomatic subjects and identified qPCR as an additional predictor. Low predictive values do not warrant prophylactic treatment but as most progressed to VL early during follow-up, careful oberservation of these subjects for at least 6 months is indicated. [ABSTRACT FROM AUTHOR]

Background: Preventative chemotherapy and mass drug administration have been identified as effective strategies for the prevention, treatment, control and elimination of several NTDs in the Asia-Pacific region. Qualitative research can provide in-depth insight into the social dynamics and processes underlying effective implementation of and adherence to mass drug administration programs. This scoping review examines published qualitative literature to examine factors influencing community perceptions and acceptability of mass drug administration approaches to control NTDs in the Asia-Pacific region., Methodology: Twenty-four peer reviewed published papers reporting qualitative data from community members and stakeholders engaged in the implementation of mass drug administration programs were identified as eligible for inclusion., Findings: This systematic scoping review presents available data from studies focussing on lymphatic filariasis, soil-transmitted helminths and scabies in eight national settings (India, Indonesia, Philippines, Bangladesh, Laos, American Samoa, Papua New Guinea, Fiji). The review highlights the profoundly social nature of individual, interpersonal and institutional influences on community perceptions of willingness to participate in mass drug administration programs for control of neglected tropical diseases (NTD). Future NTD research and control efforts would benefit from a stronger qualitative social science lens to mass drug administration implementation, a commitment to understanding and addressing the social and structural determinants of NTDs and NTD control in complex settings, and efforts to engage local communities as equal partners and experts in the co-design of mass drug administration and other efforts to prevent, treat, control and eliminate NTDs., Conclusion: For many countries in the Asia-Pacific region, the "low hanging fruit has been picked" in terms of where mass drug administration has worked and transmission has been stopped. The settings that remain-such as remote areas of Fiji and Papua New Guinea, or large, highly populated, multi-cultural urban settings in India and Indonesia-present huge challenges going forward., Competing Interests: The authors have declared that no competing interests exist.