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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]

Chikungunya can have longstanding effects on health and quality of life. Alongside the recent approval of the world's first chikungunya vaccine by the US Food and Drug Administration in November 2023 and with new chikungunya vaccines in the pipeline, it is important to understand the perspectives of stakeholders before vaccine rollout. Our study aim is to identify key programmatic considerations and gaps in Evidence-to-Recommendation criteria for chikungunya vaccine introduction. We used purposive and snowball sampling to identify global, national, and subnational stakeholders from outbreak prone areas, including Latin America, Asia, and Africa. Semi-structured in-depth interviews were conducted and analysed using qualitative descriptive methods. We found that perspectives varied between tiers of stakeholders and geographies. Unknown disease burden, diagnostics, non-specific disease surveillance, undefined target populations for vaccination, and low disease prioritisation were critical challenges identified by stakeholders that need to be addressed to facilitate rolling out a chikungunya vaccine. Future investments should address these challenges to generate useful evidence for decision-making on new chikungunya vaccine introduction. Author summary: The first vaccine to prevent chikungunya fever has been recently approved in November 2023 by the US FDA and multiple chikungunya vaccine candidates are in different phases of the development pipeline. These will be the first-ever vaccines against an alphavirus and offer new technologies for vaccine development against other viruses of the same family that may cause future epidemics. We interviewed stakeholders from areas at risk of chikungunya outbreaks across Latin America, Asia and Africa, and identified gaps in Evidence-to-Recommendation criteria that should be addressed alongside vaccine introduction. Our findings show that stakeholders from different regions prioritised chikungunya differently, but all stakeholders agreed that the unknown burden of disease, undefined target populations for vaccination and non-specific disease surveillance were challenges that needed to be addressed imminently. To address these gaps, the involvement of stakeholders in all phases of vaccine development and rollout will be crucial to uncover future challenges and to ensure vaccine equity. [ABSTRACT FROM AUTHOR]

Background: The morbidity and mortality of extraparenchymal neurocysticercosis (EP-NC) remain high and effectiveness of current medical treatment is suboptimal. Various factors have been implicated in the severity of EP-NC and in the poor response to treatment, but the possible role of host immune and endocrine systems has not yet been examined thoroughly. Methodology/Principal findings: 42 participants with EP-NC before receiving standard treatment and 25 healthy controls were included in the study. Treatment response was assessed by comparing pre/post treatment parasite volumes from 3D MRI. Prior to treatment among participants with EP-NC, specific stimulation induced an increased specific proliferative response accompanied by a significant increase in IL-4, NK, NKT, Bregs and Tregs cells, whereas in healthy controls, specific stimulation induced a significant increase in IL-1β, IL-5, CCL5, IL-6, TNF-α, NK and Bregs cells. Significant differences between participants with EP-NC and healthy controls in the specific inflammatory response were observed. Participants with EP-NC prior to treatment had significantly weaker responses of proinflammatory cytokines (IL-6, TNF-α) and NK cells, and stronger IL-4 response. Anthelmintic treatment did not promote significant peripheral immunological changes at any time, although inflammation was sustained in the cerebrospinal fluid. Serum estradiol concentration significantly decreased after anthelmintic treatment among males, and cortisol correlated negatively with IL-6 and positively with IFN-γ levels. No pre-treatment immunologic or endocrinologic parameters were significantly associated with response to treatment. Conclusion/Significance: Prior to anthelmintic treatment, EP-NC was characterized by low lymphocyte reactivity accompanied by a regulatory response, which may be involved in the lack of peripheral immunological changes during and after treatment, although a central inflammatory response was present. This weak specific peripheral response could favor the chronicity of the infection and the poor response to treatment. Our findings highlight the need for new anti-inflammatory treatment focused on the central nervous system with less systemic immunosuppressive effects. Author summary: Neurocysticercosis is a central nervous system infection with the helminth Taenia solium in its larval stage. It is a marker of poverty and remains endemic in countries of Latin America, Africa, and Asia. The severity of neurocysticercosis and the prognosis of patients depend on the location of the parasites. Extraparenchymal infection involving the subarachnoid and/or ventricular space is associated with high morbidity and mortality and a suboptimal response to current anthelminthic treatment regimens. We examined peripheral immunological parameters and hormones of 42 participants with extraparenchymal neurocysticercosis before and after treatment, and their associations with subsequent treatment response. Prior to treatment, compared with healthy controls, there was low lymphocyte reactivity with a regulatory response, which may explain the lack of peripheral immunological changes during and after treatment. This weak specific peripheral response could favor the chronicity of the infection and the poor response to treatment and should be considered in research to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Snakebite envenoming is a serious and life-threatening medical condition that predominantly affects people living in rural communities across Africa, Asia, and Latin America. As our climate changes, there is a growing concern that negative human–snake interactions will increase. Our ability to prevent and manage snakebite requires effective antivenoms as well as knowledge regarding the prevention and management of snakebite among healthcare workers and affected communities across the globe. This systematic review aims to assess existing levels of knowledge regarding snakebite prevention and management in both healthcare workers and affected communities. Methods: This review was conducted on studies reporting quantitative measurements to evaluate knowledge and practice regarding snakebite prevention and management published in major databases between 1 January 2000 and 31 December 2021. Random effects modelling was used to obtain the pooled proportion. Heterogeneity (I2) was tested, and sensitivity analyses performed. Results: Out of 3,697 records, 16 studies from 12 countries assessing 7,640 participants were included. Four of the studies were ranked as good quality studies, 9 as fair, and 3 as poor. This study results demonstrated that 56% of the study population answered the knowledge question correctly (95% CI 48% to 63%, p < 0.001). High heterogeneity was observed (I2 = 97.29%), with marginal publication bias (Egger's regression test, p = 0.0814). Participants had relatively higher knowledge concerning use of antivenom as preferred treatment, followed by snakebite prevention, knowledge of signs and symptoms of snakebite, knowledge of first-aid, and knowledge of treatment. Participants had lower knowledge relating to types of snakes and the identification of snakes. Conclusion: Adequate knowledge about snakebites and its management among the general population and healthcare workers was 56%. Healthcare workers and communities across Asia showed higher relative knowledge compared to those in Africa and the Middle East. These data suggest that further education is needed in both the general population and among healthcare workers to ensure that appropriate preventative and patient management techniques are being utilised in snakebite endemic regions. Greater local awareness of the risks and appropriate management of snakebite is required to reduce the burden of snakebite mortality and morbidity. [ABSTRACT FROM AUTHOR]

Forecasting the impacts of climate change on Aedes-borne viruses—especially dengue, chikungunya, and Zika—is a key component of public health preparedness. We apply an empirically parameterized model of viral transmission by the vectors Aedes aegypti and Ae. albopictus, as a function of temperature, to predict cumulative monthly global transmission risk in current climates, and compare them with projected risk in 2050 and 2080 based on general circulation models (GCMs). Our results show that if mosquito range shifts track optimal temperature ranges for transmission (21.3–34.0°C for Ae. aegypti; 19.9–29.4°C for Ae. albopictus), we can expect poleward shifts in Aedes-borne virus distributions. However, the differing thermal niches of the two vectors produce different patterns of shifts under climate change. More severe climate change scenarios produce larger population exposures to transmission by Ae. aegypti, but not by Ae. albopictus in the most extreme cases. Climate-driven risk of transmission from both mosquitoes will increase substantially, even in the short term, for most of Europe. In contrast, significant reductions in climate suitability are expected for Ae. albopictus, most noticeably in southeast Asia and west Africa. Within the next century, nearly a billion people are threatened with new exposure to virus transmission by both Aedes spp. in the worst-case scenario. As major net losses in year-round transmission risk are predicted for Ae. albopictus, we project a global shift towards more seasonal risk across regions. Many other complicating factors (like mosquito range limits and viral evolution) exist, but overall our results indicate that while climate change will lead to increased net and new exposures to Aedes-borne viruses, the most extreme increases in Ae. albopictus transmission are predicted to occur at intermediate climate change scenarios. [ABSTRACT FROM AUTHOR]

Background: Most smallholder farmers (SHFs) and marginalized populations (MPs) in Africa, Asia, and Latin America depend on livestock for their livelihoods. However, significant numbers of these animals do not achieve their potential, die due to disease, or transmit zoonotic diseases. Existing vaccines could prevent and control some of these diseases, but frequently the vaccines do not reach SHFs, especially MPs, making it necessary for specific vaccine adoption strategies. Principal findings: Several strategies that have the potential to increase the adoption of animal vaccines by SHFs and MPs have been identified depending on the type of vaccines involved. The strategies differed depending on whether the vaccines were aimed at diseases that cause economic losses, government-controlled diseases, or neglected diseases. The adoption of vaccines for neglected diseases presents a major challenge, because they are mostly for zoonotic diseases that produce few or no clinical signs in the animals, making it more difficult for the farmers to appreciate the value of the vaccines. Strategies can be aimed at increasing the availability of quality vaccines, so that they are produced in sufficient quantity, or aimed at increasing access and demand by SHFs and/or MPs. Some of the strategies to increase vaccine adoption might not provide a definite solution but might facilitate vaccine uptake by decreasing barriers. These strategies are varied and include technical considerations, policy components, involvement by the private sector (local and international), and innovation. Conclusions: Several strategies with the potential to reduce livestock morbidity and mortality, or prevent zoonoses in SHFs communities and MPs through vaccination, require the involvement of donors and international organisations to stimulate and facilitate sustainable adoption. This is especially the case for neglected zoonotic diseases. Support for national and regional vaccine manufacturers is also required, especially for vaccines against diseases of interest only in the developing world and public goods. [ABSTRACT FROM AUTHOR]

Canine rabies can be effectively controlled by vaccination with readily available, high-quality vaccines. These vaccines should provide protection from challenge in healthy dogs, for the claimed period, for duration of immunity, which is often two or three years. It has been suggested that, in free-roaming dog populations where rabies is endemic, vaccine-induced protection may be compromised by immuno-suppression through malnutrition, infection and other stressors. This may reduce the proportion of dogs that seroconvert to the vaccine during vaccination campaigns and the duration of immunity of those dogs that seroconvert. Vaccination coverage may also be limited through insufficient vaccine delivery during vaccination campaigns and the loss of vaccinated individuals from populations through demographic processes. This is the first longitudinal study to evaluate temporal variations in rabies vaccine-induced serological responses, and factors associated with these variations, at the individual level in previously unvaccinated free-roaming dog populations. Individual-level serological and health-based data were collected from three cohorts of dogs in regions where rabies is endemic, one in South Africa and two in Indonesia. We found that the vast majority of dogs seroconverted to the vaccine; however, there was considerable variation in titres, partly attributable to illness and lactation at the time of vaccination. Furthermore, >70% of the dogs were vaccinated through community engagement and door-to-door vaccine delivery, even in Indonesia where the majority of the dogs needed to be caught by net on successive occasions for repeat blood sampling and vaccination. This demonstrates the feasibility of achieving population-level immunity in free-roaming dog populations in rabies-endemic regions. However, attrition of immune individuals through demographic processes and waning immunity necessitates repeat vaccination of populations within at least two years to ensure communities are protected from rabies. These findings support annual mass vaccination campaigns as the most effective means to control canine rabies. [ABSTRACT FROM AUTHOR]

Background: Human toxocariasis is an important neglected disease. We performed a systematic review and meta-analysis study to estimate the global and regional prevalence of anti-Toxocara serum antibodies (referred to as 'T-seroprevalence') in human populations around the world. Methods: We searched five international databases (PubMed, EMBASE, Web of Science, SciELO and Scopus) for seroprevalence studies published from 1 January 1980 to 15 March 2019. We used random effect models to calculate the overall T-seroprevalence (with 95% CIs) in all six WHO regions and worldwide. We also conducted subgroup and linear meta-regression analyses to evaluate the impact of socio-demographic, geographical and climatic parameters on seroprevalence. Results: We identified 250 eligible studies (253 datasets) comprising 265,327 participants in 71 countries for inclusion in the present meta-analysis. The estimated global T-seroprevalence rate was 19.0% (95%CI, 16.6–21.4%; 62,927/265,327); seroprevalence was highest in the African region (37.7%; 25.7–50.6%) and lowest in the Eastern Mediterranean region (8.2%; 5.1–12.0%). The pooled seroprevalence for other WHO regions was 34.1% (20.2–49.4%) in the South-East Asia; 24.2% (16.0–33.5%) in the Western Pacific; 22.8% (19.7–26.0%) in the American; and 10.5% (8.5–12.8%) in the European regions. A significantly higher T-seroprevalence was associated with a lower income level; lower human development index (HDI); lower latitude; higher humidity; higher temperature; and higher precipitation (P-value < 0.001). Potential risk factors associated with seropositivity to Toxocara included male gender; living in a rural area; young age; close contact with dogs, cats or soil; consumption of raw meat; and the drinking of untreated water. Conclusions: The present findings indicate high levels of infection with, or exposure to Toxocara spp. in many countries, which calls for increased attention to human toxocariasis and improved measures to prevent adverse health risks of this disease. Author summary: There have been many epidemiological studies on the seroprevalence of Toxocara infection or toxocariasis in humans in individual countries, but there has been no systematic review/meta-analysis to estimate the extent of Toxocara infection or exposure in human populations worldwide. By reviewing 250 studies of 265,327 people from 71 countries, we provide the first comprehensive global estimates of T-seroprevalence in humans to date. The findings indicate that almost one fifth (19%) of the world's human population is seropositive to Toxocara. The highest seroprevalence rates were found in Africa (37.7%) and the lowest in the Eastern Mediterranean region (8.2%). Individual countries with high HDIs and high income levels usually had low T-seroprevalence rates. Our findings also showed that T-seroprevalence varies markedly among countries, according to geographical location (coordinates) and climatic features. Evidence from this study indicates that human toxocariasis is a prevalent, neglected tropical disease and potentially one of major importance to global public health. Our study emphasizes the need for governmental authorities to pay increased attention to the risks and socioeconomic impact of HT in many countries around the world, and for them to design and implement HT prevention or control programs, considering risk predictors identified here. [ABSTRACT FROM AUTHOR]