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Dengue is among the fastest-spreading vector-borne infectious disease, with outbreaks often overwhelm the health system and result in huge morbidity and mortality in its endemic populations in the absence of an efficient warning system. A large number of prediction models are currently in use globally. As such, this study aimed to systematically review the published literature that used quantitative models to predict dengue outbreaks and provide insights about the current practices. A systematic search was undertaken, using the Ovid MEDLINE, EMBASE, Scopus and Web of Science databases for published citations, without time or geographical restrictions. Study selection, data extraction and management process were devised in accordance with the 'Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies' ('CHARMS') framework. A total of 99 models were included in the review from 64 studies. Most models sourced climate (94.7%) and climate change (77.8%) data from agency reports and only 59.6% of the models adjusted for reporting time lag. All included models used climate predictors; 70.7% of them were built with only climate factors. Climate factors were used in combination with climate change factors (10.3%), both climate change and demographic factors (10.3%), vector factors (5.1%), and demographic factors (5.1%). Machine learning techniques were used for 39.4% of the models. Of these, random forest (15.4%), neural networks (23.1%) and ensemble models (10.3%) were notable. Among the statistical (60.6%) models, linear regression (18.3%), Poisson regression (18.3%), generalized additive models (16.7%) and time series/autoregressive models (26.7%) were notable. Around 20.2% of the models reported no validation at all and only 5.2% reported external validation. The reporting of methodology and model performance measures were inadequate in many of the existing prediction models. This review collates plausible predictors and methodological approaches, which will contribute to robust modelling in diverse settings and populations. Author summary: Dengue is considered as a major public health challenge and a life-threatening disease affecting people worldwide. Over the past decades, numerous forecast models have been developed to predict dengue incidence using various factors based on different geographical locations. Dengue transmission appears to be highly sensitive to climate variability and change, however quantitative models used to assess the relationship between climate change and dengue often differ due to their distribution assumptions, the nature of the relationship and the spatial and/or temporal dynamics of the response. We performed a systematic review to examine current literature surrounding existing quantitative models based on development methodology, predictor variable used and model performance. Our analysis demonstrates several shortcomings in current modelling practice, and advocates for the use of real time primary predictor data, the incorporation of non-climatic parameters as predictors and more comprehensive reporting of model development techniques and validation. This review collates methodological approaches adopted in the modelling practices in the field across current literature. This will provide an evidence-based framework for upgrading future modelling practice to develop more accurate predictive models with robust techniques. In turn, this also provided an opportunity for the effective distribution of limited public health resources to prepare for demand. [ABSTRACT FROM AUTHOR]

T cells recognize their ligand, the peptide major histocompatibility complex (MHC), via the T-cell receptor (TCR), which is composed of covalently linked α and β or γ and δ chains. This recognition is critical for T-cell ontogeny and controls the selection, activation, and function of T lymphocytes. Specific TCR αβ variable regions have been associated with immunopathogenesis of Chagas disease. Here, we present a systematic review that compiles experimental in vivo and human data regarding the preferential expression of variable alpha (Vα) and variable beta (Vβ) chain regions in Trypanosoma cruzi infection. The original studies indexed in PubMed/Medline, Scopus, and Web of Science databases were screened according to the PRISMA strategy. The analysis showed that expression of TCR Vα subfamilies were evaluated in one human study, and, unlike TCR Vβ, TCR Vα presented a more restricted usage. Despite the great variability in the usage of TCR Vβ regions in human Chagas disease, a down-regulation of TCR Vβ5 expression by T cells from patients in the acute phase of the disease was shown. Opposingly, this TCR region was found overly expressed in CD4+ T cells from chronic Chagas patients. It was also demonstrated that murine Vβ9+ T cells derived from nonlymphoid organs of T. cruzi-infected animals had a modulatory profile, while splenic Vβ9+ T cells produced inflammatory cytokines, indicating that although they display the same TCR Vβ region usage, these cells are functionally distinct. Despite the limitations of few papers and year of publication of the studies, compiling the data derived from them reveals that further investigation of TCR usage will point to their potential role in protective or pathogenic responses, as biomarkers of disease progression, and in the search for dominant peptides potentially useful for the development of vaccines or therapies. Author summary: Chagas disease is a neglected tropical disease, caused by infection with Trypanosoma cruzi. Differential expression of certain T-cell receptor (TCR) variable regions has been associated with the immunopathogenesis of Chagas disease. Here, we present a systematic review that compiled experimental in vivo and human data regarding the preferential expression of TCR alpha and beta chain variable regions in Chagas disease. The original studies indexed in the PubMed/Medline, Scopus, and Web of Science databases were screened according to the PRISMA strategy. Despite the great variability in the use of TCR Vβ in T. cruzi infection, the outcomes indicate that there is a down-regulation of TCR Vβ5 expression in T cells from patients in the acute phase of Chagas disease. However, this region is preferentially expressed by CD4+ T cells from chronic Chagas patients. Additionally, it has been demonstrated that murine Vβ9+ T cells derived from nonlymphoid organs displayed a modulatory profile, while splenic Vβ9+ T cells produced inflammatory cytokines, indicating that although they express the same TCR Vβ region, these cells are functionally distinct. Information on TCR expression, specificity and function have critical impact on vaccine design. [ABSTRACT FROM AUTHOR]

Background: The awareness of non-malarial febrile illnesses (NMFIs) has been on the rise over the last decades. Therefore, we undertook a systematic literature review and meta-analysis of causative agents of non-malarial fevers on the African continent. Methodology: We searched for literature in African Journals Online, EMBASE, PubMed, Scopus, and Web of Science databases to identify aetiologic agents that had been reported and to determine summary estimates of the proportional morbidity rates (PMr) associated with these pathogens among fever patients. Findings: A total of 133 studies comprising 391,835 patients from 25 of the 54 African countries were eligible. A wide array of aetiologic agents were described with considerable regional differences among the leading agents. Overall, bacterial pathogens tested from blood samples accounted for the largest proportion. The summary estimates from the meta-analysis were low for most of the agents. This may have resulted from a true low prevalence of the agents, the failure to test for many agents or the low sensitivity of the diagnostic methods applied. Our meta-regression analysis of study and population variables showed that diagnostic methods determined the PMr estimates of typhoidal Salmonella and Dengue virus. An increase in the PMr of Klebsiella spp. infections was observed over time. Furthermore, the status of patients as either inpatient or outpatient predicted the PMr of Haemophilus spp. infections. Conclusion: The small number of epidemiological studies and the variety of NMFI agents on the African continent emphasizes the need for harmonized studies with larger sample sizes. In particular, diagnostic procedures for NMFIs should be standardized to facilitate comparability of study results and to improve future meta-analyses. Reliable NMFI burden estimates will inform regional public health strategies. Author summary: Previous systematic reviews have highlighted the research priorities of causative agents for non-malarial febrile illnesses by counting the number of publications attributed to an agent. However, proportional morbidity rates are calculated by dividing the number of cases with a specific disease (numerator) by the total number of diagnosed fever cases (denominator) and are better indicators of the relative importance of aetiological agents in a population. Therefore, we present the leading causes of non-malarial febrile illnesses in African patients in both healthcare and community settings. Preference is given to HIV-negative patients when data could be found. We also determined summary estimates of Brucella spp., Chikungunya virus, Dengue virus, Haemophilus spp., Klebsiella spp., Leptospira spp., non-typhoidal Salmonella spp., typhoidal Salmonella spp., Staphylococcus spp., and Streptococcus spp. The wide array of aetiological agents causing febrile illnesses on the African continent does not only complicate malaria control programs but may also hamper response to epidemic and pandemic illnesses such as Ebola and COVID-19. The harmonisation of diagnostics and study designs will reduce between-study differences, which may result in better estimates of disease burden on the continent and in the different African regions. This information is important for Pan-African surveillance and control efforts. [ABSTRACT FROM AUTHOR]

Background: Tungiasis is a neglected disease caused by Tunga penetrans that can be complicated by secondary infections and local tissue destruction. Adequate treatment is important, especially in vulnerable populations; potential treatment options proposed range from surgical extraction to the use of oral and topical medications. We aimed to perform a systematic review to assess the efficacy of topical, oral and surgical interventions for the treatment of tungiasis. Methodology/Principal findings: The present review is registered in PROSPERO (CRD42021234741). On September 1, 2020, we searched PubMed, EMBASE, Scopus, Web of Science, Science Direct, Scielo and LILACS BVS. We included clinical trials and longitudinal observational studies that evaluated any topical, systemic or mechanical treatment for tungiasis. We used the Revised Cochrane Risk of Bias (RoB) Tool for Randomized Trials for clinical trial analysis. Qualitative and quantitative descriptive syntheses were performed. Our search strategy resulted in 3376 references. Subsequently, 2568 titles/abstracts and 114 full texts were screened. We finally included 19 articles; 9 were classified as clinical trials. Two and 3 articles presented low and some RoB, respectively, according to the tool. Only two articles tested the efficacy of oral medications (niridazole, ivermectin), with discouraging results. Six clinical trials evaluated topical products for the treatment of tungiasis; 2 evaluated dimeticone-based compounds and reported positive results in lesion reduction and cure. None reported significant adverse reactions. Surgical extraction was evaluated only in observational studies. Conclusions/Significance: We conclude that, although surgical extraction is the most commonly used treatment, there is sufficient evidence supporting the use of occlusive agents, especially manufactured dimeticone-based products. Author summary: Tungiasis is a disease caused by Tunga penetrans that affects regions with low socioeconomic status and a lack of proper sanitation. The disease usually has a self-limiting course or can be cured by simple extraction, but complications are not uncommon. In vulnerable populations, such as indigenous communities, children and people with disseminated tungiasis, the development of new treatment strategies is essential for the prevention of undesirable secondary outcomes. We performed a comprehensive systematic review of the literature by searching the most important scientific databases: PubMed, EMBASE, Scopus, Web of Science, Science Direct, Scielo and LILACS BVS. We aimed to assess the efficacy of topical, oral and surgical interventions for the treatment of tungiasis. We included 19 articles, 9 of which were classified as clinical trials. Six clinical trials evaluated topical products for the treatment of tungiasis; 2 evaluated dimeticone-based compounds and reported positive results in lesion reduction and cure. None reported significant adverse reactions. We concluded that, although mechanical extraction is the most commonly used treatment, there is sufficient evidence supporting the use of occlusive agents, especially manufactured dimeticone-based products. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization's (WHO) Neglected Tropical Disease (NTD) Road Map for 2021–2030 was recently endorsed by all member states at the World Health Assembly in November 2020. Although only 3 of the 20 NTDs are endemic in Canada (i.e., echinococcosis, rabies, and scabies), the Canadian research community has contributed to advancing the knowledge base of all 20 NTDs. Previous research comprehensively detailed Canadian research on 11 NTDs between 1950 and 2010 using a network analysis approach. The specific objective of the present analysis was to update the publication record over the last decade (2010–2019) to include all 20 NTDs. Materials and methods: A bibliometric analysis was conducted in Scopus and Web of Science databases (for English or French articles published between January 1, 2010 and December 31, 2019) using appropriate search terms for each of the 20 NTDs and where at least 1 of the authors had a Canadian institution address. A 21st search was added to include publications including multiple NTDs or a discussion of NTDs in general. Following assessment of inclusion and exclusion criteria, 2 reviewers independently screened all abstracts, with discordant observations rereviewed to arrive at an agreement. Duplicates were removed. Results: A total of 1,790 publications were retrieved (1,738 with a disease–specific NTD focus and 52 with a general NTD focus, resulting in 1,659 unique publications), giving an average of over 160 articles per year. Over 80% were classified as full–length research articles. The top 3 journals in terms of frequency were PLOS Neglected Tropical Diseases, PLOS ONE, and the American Journal of Tropical Medicine and Hygiene. Authors' institutions were from all Canadian provinces. While all 20 NTDs were addressed in these publications, the 5 most commonly studied were leishmaniasis, dengue fever and chikungunya, Chagas disease, soil–transmitted helminthiases, and rabies. Conclusions: Canadian researchers across the country have contributed to the evidence base of all 20 NTDs, publishing an average of over 160 publications per year between 2010 and 2019. As WHO NTD Road Map 2021–2030 rolls out globally, the Canadian research community, in collaboration with its partners and in solidarity with people living in vulnerable circumstances in endemic regions worldwide, is well positioned to meet future research challenges so that the goal of eliminating the disease burden attributable to NTDs can be achieved. [ABSTRACT FROM AUTHOR]