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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: Despite the use of numerous methods of control measures, mosquito populations and mosquito-borne diseases are still increasing globally. Evidence-based action thresholds to initiate or intensify control activities have been identified as essential in reducing mosquito populations to required levels at the correct/optimal time. This systematic review was conducted to identify different mosquito control action thresholds existing across the world and associated surveillance and implementation characteristics. Methodology/Principal findings: Searches for literature published from 2010 up to 2021 were performed using two search engines, Google Scholar and PubMed Central, according to PRISMA guidelines. A set of inclusion/exclusion criteria were identified and of the 1,485 initial selections, only 87 were included in the final review. Thirty inclusions reported originally generated thresholds. Thirteen inclusions were with statistical models that seemed intended to be continuously utilized to test the exceedance of thresholds in a specific region. There was another set of 44 inclusions that solely mentioned previously generated thresholds. The inclusions with "epidemiological thresholds" outnumbered those with "entomological thresholds". Most of the inclusions came from Asia and those thresholds were targeted toward Aedes and dengue control. Overall, mosquito counts (adult and larval) and climatic variables (temperature and rainfall) were the most used parameters in thresholds. The associated surveillance and implementation characteristics of the identified thresholds are discussed here. Conclusions/Significance: The review identified 87 publications with different mosquito control thresholds developed across the world and published during the last decade. Associated surveillance and implementation characteristics will help organize surveillance systems targeting the development and implementation of action thresholds, as well as direct awareness towards already existing thresholds for those with programs lacking available resources for comprehensive surveillance systems. The findings of the review highlight data gaps and areas of focus to fill in the action threshold compartment of the IVM toolbox. Author summary: Many different methods are used and new methods are evolving to control nuisance and vector mosquito populations across the world. Implementation of such control methods at the optimal time has been identified as critical to maintaining the populations below unacceptable levels. The establishment of evidenced-based action thresholds is thus encouraged to achieve maximum results under available resources. This review was conducted to identify different action thresholds published worldwide since 2010 and to understand the associated surveillance characteristics. Only 87 publications filtered through the initial database identification of 1,485 publications were included in the review. Thirty inclusions reported originally generated thresholds, 13 inclusions reported a statistical method with a computable action threshold model, and 44 inclusions mentioned only previously generated thresholds that were used in their study. Overall, the inclusions with thresholds that directly related to disease transmission conditions ("epidemiological thresholds") outnumbered the inclusions with thresholds that directly related to mosquito abundance. The majority of the thresholds originated in Asia targeting dengue and dengue vectors. The review discusses the associated surveillance characteristics such as the possibility of using external data (previously recorded data), spatial and temporal variations in data used, and the importance of an adequate lead time to initiate control interventions that would help guide to plan better surveillance programs for the development of action thresholds. [ABSTRACT FROM AUTHOR]

Background: Foodborne trematodiases (FBTs) are a group of trematodes targeted for control as part of the World Health Organization (WHO) road map for neglected tropical diseases from 2021 to 2030. Disease mapping; surveillance; and capacity, awareness, and advocacy building are critical to reach the 2030 targets. This review aims to synthesise available data on FBT prevalence, risk factors, prevention, testing, and treatment. Methods: We searched the scientific literature and extracted prevalence data as well as qualitative data on the geographical and sociocultural risk factors associated with infection, preventive/protective factors, and methods and challenges of diagnostics and treatment. We also extracted WHO Global Health Observatory data representing the countries that reported FBTs during 2010 to 2019. Results: One hundred and fifteen studies reporting data on any of the 4 FBTs of focus (Fasciola spp., Paragonimus spp., Clonorchis sp., and Opisthorchis spp.) were included in the final selection. Opisthorchiasis was the most commonly reported and researched FBT, with recorded study prevalence ranging from 0.66% to 88.7% in Asia, and this was the highest FBT prevalence overall. The highest recorded study prevalence for clonorchiasis was 59.6%, reported in Asia. Fascioliasis was reported in all regions, with the highest prevalence of 24.77% reported in the Americas. The least data was available on paragonimiasis, with the highest reported study prevalence of 14.9% in Africa. WHO Global Health Observatory data indicated 93/224 (42%) countries reported at least 1 FBT and 26 countries are likely co-endemic to 2 or more FBTs. However, only 3 countries had conducted prevalence estimates for multiple FBTs in the published literature between 2010 to 2020. Despite differing epidemiology, there were overlapping risk factors for all FBTs in all geographical areas, including proximity to rural and agricultural environments; consumption of raw contaminated food; and limited water, hygiene, and sanitation. Mass drug administration and increased awareness and health education were commonly reported preventive factors for all FBTs. FBTs were primarily diagnosed using faecal parasitological testing. Triclabendazole was the most reported treatment for fascioliasis, while praziquantel was the primary treatment for paragonimiasis, clonorchiasis, and opisthorchiasis. Low sensitivity of diagnostic tests as well as reinfection due to continued high-risk food consumption habits were common factors. Conclusion: This review presents an up-to-date synthesis on the quantitative and qualitative evidence available for the 4 FBTs. The data show a large gap between what is being estimated and what is being reported. Although progress has been made with control programmes in several endemic areas, sustained effort is needed to improve surveillance data on FBTs and identify endemic and high-risk areas for environmental exposures, through a One Health approach, to achieve the 2030 goals of FBT prevention. [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]

Chronic topical cases of Sporotrichosis, a chronic fungal infection caused by the ubiquitously present cryptic members of the Sporothrix species complex, are treated with oral administrations of itraconazole. However, severe pulmonary or disseminated cases require repeated intra-venous doses of amphotericin B or even surgical debridement of the infected tissue. The unavoidable adverse side-effects of the current treatments, besides the growing drug resistance among Sporothrix genus, demands exploration of alternative therapeutic options. Medicinal herbs, due to their multi-targeting capacity, are gaining popularity amidst the rising antimicrobial recalcitrance. Withania somnifera is a well-known medicinal herb with reported antifungal activities against several pathogenic fungal genera. In this study, the antifungal effect of the whole plant extract of W. somnifera (WSWE) has been explored for the first time, against an itraconazole resistant strain of S. globosa. WSWE treatment inhibited S. globosa yeast form growth in a dose-dependent manner, with IC50 of 1.40 mg/ml. Minimum fungicidal concentration (MFC) was found to be 50 mg/ml. Sorbitol protection and ergosterol binding assays, revealed that anti-sporotrichotic effects of WSWE correlated well with the destabilization of the fungal cell wall and cell membrane. This observation was validated through dose-dependent decrease in overall ergosterol contents in WSWE-treated S. globosa cells. Compositional analysis of WSWE through high performance liquid chromatography (HPLC) exhibited the presence of several anti-microbial phytochemicals like withanone, withaferin A, withanolides A and B, and withanoside IV and V. Withanone and withaferin A, purified from WSWE, were 10–20 folds more potent against S. globosa than WSWE, thus, suggesting to be the major phytocompounds responsible for the observed anti-sporotrichotic activity. In conclusion, this study has demonstrated the anti-sporotrichotic property of the whole plant extract of W. somnifera against S. globosa that could be further explored for the development of a natural antifungal agent against chronic Sporotrichosis. Author summary: Sporotrichosis, commonly known as 'rose gardener's disease' is a rare but chronic fungal infection caused by several pathogenic members of Sporothrix. Although rare, Sporotrichosis can spread to the lungs or whole body, and thus, could be fatal. However, due to low frequency of its occurrence, scientific research on Sporotrichosis has been rather limited. To exacerbate the situation, many Sporothrix members have developed resistance against the common anti-fungal agents used to treat fungal infections. Many medicinal herbs are being explored for their effectiveness against drug-resistant microorganisms. In this connection, the well-known medicinal plant, Withania somnifera, commonly known as Winter cherry in English and Ashwagandha in Hindi, has been explored for its anti-fungal potentials against several pathogenic fungi. However, to the best of our knowledge, anti-fungal effect of W. somnifera against Sporothrix has not been assessed yet. Therefore, this study was conducted to investigate the anti-fungal potentials of Withania somnifera whole plant extract (WSWE) against Sporothrix globosa, known to cause Sporotrichosis in Asia. This study demonstrated significant anti-sporotrichotic effect of WSWE, which could be further explored for developing an alternative natural treatment for Sporotrichosis. [ABSTRACT FROM AUTHOR]

Background: Japanese encephalitis (JE) virus (JEV) remains a leading cause of neurological infection across Asia. The high lethality of disease and absence of effective therapies mean that standardised animal models will be crucial in developing therapeutics. However, published mouse models are heterogeneous. We performed a systematic review, meta-analysis and meta-regression of published JEV mouse experiments to investigate the variation in model parameters, assess homogeneity and test the relationship of key variables against mortality. Methodology/ Principal findings: A PubMed search was performed up to August 2020. 1991 publications were identified, of which 127 met inclusion criteria, with data for 5026 individual mice across 487 experimental groups. Quality assessment was performed using a modified CAMARADES criteria and demonstrated incomplete reporting with a median quality score of 10/17. The pooled estimate of mortality in mice after JEV challenge was 64.7% (95% confidence interval 60.9 to 68.3) with substantial heterogeneity between experimental groups (I^2 70.1%, df 486). Using meta-regression to identify key moderators, a refined dataset was used to model outcome dependent on five variables: mouse age, mouse strain, virus strain, virus dose (in log10PFU) and route of inoculation. The final model reduced the heterogeneity substantially (I^2 38.9, df 265%, df 241), explaining 54% of the variability. Conclusion/ Significance: This is the first systematic review of mouse models of JEV infection. Better adherence to CAMARADES guidelines may reduce bias and variability of reporting. In particular, sample size calculations were notably absent. We report that mouse age, mouse strain, virus strain, virus dose and route of inoculation account for much, though not all, of the variation in mortality. This dataset is available for researchers to access and use as a guideline for JEV mouse experiments. Author summary: Japanese encephalitis (JE) virus (JEV) remains a leading cause of brain infection across Asia, resulting in considerable death and disability. No effective treatment exists. Mouse models are fundamental to evaluate novel treatments. We aimed to perform the first systematic literature review and data synthesis of JEV infection in mouse models. We identified an abundance of experimental data in the field, with 127 studies meeting the inclusion criteria involving a total of 5026 individual mice. Overall, 64.7% of mice died after JEV infection. However, there was incomplete reporting in publications and considerable variability in the results. In summary, the findings support the ongoing use of mouse models of JEV infection and inform researchers in the field in refining their experiments. Key factors affecting variation in mortality across studies that need to be carefully considered in study design are mouse age, mouse strain, virus strain, virus dose and route of inoculation. We highlight the need for researchers to adhere to reporting guidelines in preparing manuscripts for publication. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus is an acute febrile illness caused by intracellular bacteria from the genus Orientia. It is estimated that one billion people are at risk, with one million cases annually mainly affecting rural areas in Asia-Oceania. Relative to its burden, scrub typhus is understudied, and treatment recommendations vary with poor evidence base. These knowledge gaps could be addressed by establishing an individual participant-level data (IPD) platform, which would enable pooled, more detailed and statistically powered analyses to be conducted. This study aims to assess the characteristics of scrub typhus treatment studies and explore the feasibility and potential value of developing a scrub typhus IPD platform to address unanswered research questions. Methodology/principal findings: We conducted a systematic literature review looking for prospective scrub typhus clinical treatment studies published from 1998 to 2020. Six electronic databases (Ovid Embase, Ovid Medline, Ovid Global Health, Cochrane Library, Scopus, Global Index Medicus), ClinicalTrials.gov, and WHO ICTRP were searched. We extracted data on study design, treatment tested, patient characteristics, diagnostic methods, geographical location, outcome measures, and statistical methodology. Among 3,100 articles screened, 127 were included in the analysis. 12,079 participants from 12 countries were enrolled in the identified studies. ELISA, PCR, and eschar presence were the most commonly used diagnostic methods. Doxycycline, azithromycin, and chloramphenicol were the most commonly administered antibiotics. Mortality, complications, adverse events, and clinical response were assessed in most studies. There was substantial heterogeneity in the diagnostic methods used, treatment administered (including dosing and duration), and outcome assessed across studies. There were few interventional studies and limited data collected on specific groups such as children and pregnant women. Conclusions/significance: There were a limited number of interventional trials, highlighting that scrub typhus remains a neglected disease. The heterogeneous nature of the available data reflects the absence of consensus in treatment and research methodologies and poses a significant barrier to aggregating information across available published data without access to the underlying IPD. There is likely to be a substantial amount of data available to address knowledge gaps. Therefore, there is value for an IPD platform that will facilitate pooling and harmonisation of currently scattered data and enable in-depth investigation of priority research questions that can, ultimately, inform clinical practice and improve health outcomes for scrub typhus patients. Author summary: Scrub typhus is a febrile illness most commonly found in rural tropical areas. It is caused by a Gram-negative bacteria belonging to the family Rickettsiaceae and transmitted by mites when they feed on vertebrates. There is an estimate of one million cases annually, with an estimated one billion people at risk, mostly in Asia-Oceania. But relative to the scale of the problem, scrub typhus is largely understudied. Evidence-based treatment recommendations by policymakers vary or are non-existent. We searched databases and registries for prospective scrub typhus clinical treatment studies published from 1998 to 2020 and reviewed them. Data from clinical trials and particularly for specific groups, such as pregnant women and children, were minimal. The methods used to measure treatment efficacy were heterogeneous, making it difficult to directly compare or conduct a meta-analysis based on aggregated data. One way to improve the current level of evidence would be by pooling and analysing individual participant-level data (IPD), i.e. the raw data from individual participants in completed studies. This review demonstrated that there is scope for developing a database for individual participant data to enable more detailed analyses. IPD meta-analyses could be a way to address knowledge gaps such as optimum dosing for children and pregnant women. [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.