Global prevalence and case fatality rate of Enterovirus D68 infections, a systematic review and meta-analysis.

A substantial amount of epidemiological data has been reported on Enterovirus D68 (EV-D68) infections after the 2014 outbreak. Our goal was to map the case fatality rate (CFR) and prevalence of current and past EV-D68 infections. We conducted a systematic review (PROSPERO, CRD42021229255) with published articles on EV-68 infections in PubMed, Embase, Web of Science and Global Index Medicus up to January 2021. We determined prevalences using a model random effect. Of the 4,329 articles retrieved from the databases, 89 studies that met the inclusion criteria were from 39 different countries with apparently healthy individuals and patients with acute respiratory infections, acute flaccid myelitis and asthma-related diseases. The CFR estimate revealed occasional deaths (7/1353) related to EV-D68 infections in patients with severe acute respiratory infections. Analyses showed that the combined prevalence of current and past EV-D68 infections was 4% (95% CI = 3.1-5.0) and 66.3% (95% CI = 40.0-88.2), respectively. The highest prevalences were in hospital outbreaks, developed countries, children under 5, after 2014, and in patients with acute flaccid myelitis and asthma-related diseases. The present study shows sporadic deaths linked to severe respiratory EV-D68 infections. The study also highlights a low prevalence of current EV-D68 infections as opposed to the existence of EV-D68 antibodies in almost all participants of the included studies. These findings therefore highlight the need to implement and/or strengthen continuous surveillance of EV-D68 infections in hospitals and in the community for the anticipation of the response to future epidemics.

Hepatitis B, C and D virus infections and risk of hepatocellular carcinoma in Africa: A meta-analysis including sensitivity analyses for studies comparable for confounders.

INTRODUCTION: Africa denotes unique facies for hepatocellular carcinoma (HCC) characterized by a conjunction of low sensitization, restricted access to diagnosis and treatment and associated with the highest incidence and mortality in the world. We investigated whether hepatitis B (HBV), C (HCV) and D (VHD) viruses were etiological agents of HCC in Africa. METHODS: Relevant articles were searched in PubMed, Web of Science, African Index Medicus, and African Journal Online databases, as well as manual searches in relevant reviews and included articles. Analytical studies from Africa evaluating the association between HCC development and HBV, HCV, and HDV were included. Relevant studies were selected, data extracted, and the risk of bias assessed independently by at least 2 investigators. The association was estimated using odds ratios (OR) and their 95% confidence interval (95% CI) determined by a random-effects model. Sources of heterogeneity were determined by subgroup analyses. RESULTS: A total of 36 case-control studies were included. With controls having non-hepatic disease, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBeAg (OR = 19.9; 95% CI = [3.7-105.2]), HBsAg (OR = 9.9; 95%) CI = [6.2-15.6]) and DNA (OR = 8.9; 95% CI = [5.9-13.4]); HCV (Anti-HCV (OR = 9.4; 95% CI = [6.3-14.0]) and RNA (OR = 16.5; 95% CI = [7.8-34.6]); HDV (Anti-VHD, (OR = 25.8; 95% CI = [5.9-112.2]); and HBV/HCV coinfections (HBV DNA/HCV RNA (OR = 22.5; 95% CI = [1.3-387.8]). With apparently healthy controls, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBsAg, (OR = 8.9; 95% CI = [6.0-13.0]); HCV (Anti-HCV, (OR = 7.7; 95% CI = [5.6-10.6]); and HBV/HCV coinfections (HBsAg/Anti-HCV (OR = 7.8; 95% CI = [4.4-13.6]) Substantial heterogeneity and the absence of publication bias were recorded for these results. CONCLUSIONS: In Africa, HBV/HCV coinfections and HBV, HCV, and HDV infections are associated with an increased risk of developing HCC. The implementation of large-scale longitudinal and prospective studies including healthy participants to search for early biomarkers of the risk of progression to HCC is urgently needed.

Diabetes mellitus and tuberculosis, a systematic review and meta-analysis with sensitivity analysis for studies comparable for confounders.

INTRODUCTION: Meta-analyses conducted so far on the association between diabetes mellitus (DM) and the tuberculosis (TB) development risk did not sufficiently take confounders into account in their estimates. The objective of this systematic review was to determine whether DM is associated with an increased risk of developing TB with a sensitivity analyses incorporating a wider range of confounders including age, gender, alcohol consumption, smoke exposure, and other comorbidities. METHODS: Pubmed, Embase, Web of Science and Global Index Medicus were queried from inception until October 2020. Without any restriction to time of study, geographical location, and DM and TB diagnosis approaches, all observational studies that presented data for associations between DM and TB were included. Studies with no abstract or complete text, duplicates, and studies with wrong designs (review, case report, case series, comment on an article, and editorial) or populations were excluded. The odds ratios (OR) and their 95% confidence intervals were estimated by a random-effect model. RESULTS: The electronic and manual searches yielded 12,796 articles of which 47 were used in our study (23 case control, 14 cross-sectional and 10 cohort studies) involving 503,760 cases (DM or TB patients) and 3,596,845 controls. The size of the combined effect of TB risk in the presence of DM was OR = 2.3, 95% CI = [2.0-2.7], I2 = 94.2%. This statistically significant association was maintained in cohort (OR = 2.0, CI 95% = [1.5-2.4], I2 = 94.3%), case control (OR = 2.4, CI 95% = [2.0-2.9], I2 = 93.0%) and cross-sectional studies (OR = 2.5, CI 95% = [1.8-3.5], I2 = 95.2%). The association between DM and TB was also maintained in the sensitivity analysis including only studies with similar proportions of confounders between cases and controls. The substantial heterogeneity observed was mainly explained by the differences between geographic regions. CONCLUSIONS: DM is associated with an increased risk of developing latent and active TB. To further explore the role of DM in the development of TB, more investigations of the biological mechanisms by which DM increases the risk of TB are needed. REVIEW REGISTRATION: PROSPERO, CRD42021216815.

Global prevalence of hepatitis B virus serological markers among healthcare workers: A systematic review and meta-analysis.

BACKGROUND: The hepatitis B virus (HBV) infection is a global public health concern that affects about 2 billion people and causes 1 million people deaths yearly. HBV is a blood-borne disease and healthcare workers (HCWs) are a high-risk group because of occupational hazard to patients' blood. Different regions of the world show a highly variable proportion of HCWs infected and/or immunized against HBV. Global data on serologic markers of HBV infection and immunization in HCWs are very important to improve strategies for HBV control. AIM: To determine the worldwide prevalence of HBV serological markers among HCWs. METHODS: In this systematic review and meta-analyses, we searched PubMed and Excerpta Medica Database (Embase) to identify studies published between 1970 and 2019 on the prevalence of HBV serological markers in HCWs worldwide. We also manually searched for references of relevant articles. Four independent investigators selected studies and included those on the prevalence of each of the HBV serological markers including hepatitis B surface antigen (HBsAg), hepatitis e antigen (HBeAg), immunoglobulin M anti-HBc, and anti-HBs. Methodological quality of eligible studies was assessed and random-effect model meta-analysis resulted in the pooled prevalence of HBV serological markers HBV infection in HCWs. Heterogeneity (I²) was assessed using the χ² test on Cochran's Q statistic and H parameters. Heterogeneity' sources were explored through subgroup and metaregression analyses. This study is registered with PROSPERO, number CRD42019137144. RESULTS: We reviewed 14059 references, out of which 227 studies corresponding to 448 prevalence data among HCWs (224936 HCWs recruited from 1964 to 2019 in 71 countries) were included in this meta-analysis. The pooled seroprevalences of current HBsAg, current HBeAg, and acute HBV infection among HCWs were 2.3% [95% confidence interval (CI): 1.9-2.7], 0.2% (95%CI: 0.0-1.7), and 5.3% (95%CI: 1.4-11.2), respectively. The pooled seroprevalences of total immunity against HBV and immunity acquired by natural HBV infection in HCWs were 56.6% (95%CI: 48.7-63.4) and 9.2% (95%CI: 6.8-11.8), respectively. HBV infection was more prevalent in HCWs in low-income countries, particularly in Africa. The highest immunization rates against HBV in HCWs were recorded in urban areas and in high-income countries including Europe, the Eastern Mediterranean and the Western Pacific. CONCLUSION: New strategies are needed to improve awareness, training, screening, vaccination, post-exposure management and treatment of HBV infection in HCWs, and particularly in low-income regions.

Incidence and seroprevalence of rabies virus in humans, dogs and other animal species in Africa, a systematic review and meta-analysis.

Rabies is transmitted to humans mainly by dogs but also by other animal species. Reliable data on the incidence of Rabies virus (RABV) in humans, dogs, and other animal species in Africa, could be essential in the implementation of a global strategic plan to eliminate the RABV by 2030 as adopted by the WHO, OIE, and FAO. We searched the Pubmed, Embase, Scopus, African Journal Online, and African Index Medicus databases for relevant studies that report data on the incidence of RABV in Africa up to February 17, 2020. Information on active and past RABV exposures in various categories of dogs, humans and other animal species were extracted. Incidence and seroprevalence estimates were pooled using a random-effect meta-analysis. We included 73 articles which provided 142 RABV incidence and seroprevalence records in 21 African countries. The estimated incidence of RABV in 222 humans, 15,600 dogs, and 12,865 other animal species was 83.4% (95% CI = 64.6-96.5), 44.1% (95% CI = 35.1-53.4), and 41.4% (95% CI = 29.6-53.8), respectively. The estimated seroprevalence of RABV in 420 humans, 3577 dogs, and 8,55 other animal species was 33.8% (95% CI = 21.9-46.8), 19.8% (95% CI = 13.3-27.3), and 3.6% (95% CI = 0.3-9.2), respectively. The incidence of RABV in general was higher in suspected rabid dogs, other animal species of the Orders Perissodactyla, Artiodactyla and Carnivora. The incidence of RABV was higher for humans in regions of West and East Africa, for dogs in urban areas and in regions of Central and South Africa, and for animals of the order Perissodactyla in urban areas. This meta-analysis demonstrated a high incidence of RABV in Africa. Itis necessary to improve surveillance system to provide reliable data on RABV in Africa, essential for the implementation of an effective control strategy.

Association between early viral LRTI and subsequent wheezing development, a meta-analysis and sensitivity analyses for studies comparable for confounding factors.

INTRODUCTION: Consideration of confounding factors about the association between Lower Respiratory Tract Infections (LRTI) in childhood and the development of subsequent wheezing has been incompletely described. We determined the association between viral LRTI at ≤ 5 years of age and the development of wheezing in adolescence or adulthood by a meta-analysis and a sensitivity analysis including comparable studies for major confounding factors. METHODS: We performed searches through Pubmed and Global Index Medicus databases. We selected cohort studies comparing the frequency of subsequent wheezing in children with and without LRTI in childhood regardless of the associated virus. We extracted the publication data, clinical and socio-demographic characteristics of the children, and confounding factors. We analyzed data using random effect model. RESULTS: The meta-analysis included 18 publications (22 studies) that met the inclusion criteria. These studies showed that viral LRTI in children ≤ 3 years was associated with an increased risk of subsequent development of wheezing (OR = 3.1, 95% CI = 2.4-3.9). The risk of developing subsequent wheezing was conserved when considering studies with comparable groups for socio-demographic and clinical confounders. CONCLUSIONS: When considering studies with comparable groups for most confounding factors, our results provided strong evidence for the association between neonatal viral LRTI and the subsequent wheezing development. Further studies, particularly from lower-middle income countries, are needed to investigate the role of non-bronchiolitis and non-HRSV LRTI in the association between viral LRTI in childhood and the wheezing development later. In addition, more studies are needed to investigate the causal effect between childhood viral LRTI and the wheezing development later. TRIAL REGISTRATION: Review registration: PROSPERO, CRD42018116955; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018116955.

Worldwide epidemiology of Crimean-Congo Hemorrhagic Fever Virus in humans, ticks and other animal species, a systematic review and meta-analysis.

There are uncertainties about the global epidemiological data of infections due to Crimean-Congo hemorrhagic fever virus (CCHFV). We estimated the global case fatality rate (CFR) of CCHFV infections and the prevalence of CCHFV in humans, ticks and other animal species. We also explored the socio-demographic and clinical factors that influence these parameters. In this systematic review with meta-analyses we searched publications from database inception to 03rd February 2020 in Pubmed, Scopus, and Global Index Medicus. Studies included in this review provided cross-sectional data on the CFR and/or prevalence of one or more targets used for the detection of CCHFV. Two independent investigators selected studies to be included. Data extraction and risk of bias assessment were conducted independently by all authors. Data collected were analysed using a random effect meta-analysis. In all, 2345 records were found and a total of 312 articles (802 prevalence and/or CFR data) that met the inclusion criteria were retained. The overall CFR was 11.7% (95% CI = 9.1-14.5), 8.0% (95% CI = 1.0-18.9), and 4.7% (95% CI = 0.0-37.6) in humans with acute, recent, and past CCHFV infections respectively. The overall CCHFV acute infections prevalence was 22.5% (95% CI = 15.7-30.1) in humans, 2.1% (95% CI = 1.3-2.9) in ticks, and 4.5% (95% CI = 1.9-7.9) in other animal species. The overall CCHFV recent infections seroprevalence was 11.6% (95% CI = 7.9-16.4) in humans and 0.4% (95% CI = 0.0-2.9) in other animal species. The overall CCHFV past infections seroprevalence was 4.3% (95% CI = 3.3-5.4) in humans and 12.0% (95% CI = 9.9-14.3) in other animal species. CFR was higher in low-income countries, countries in the WHO African, South-East Asia and Eastern Mediterranean regions, in adult and ambulatory patients. CCHFV detection rate in humans were higher in CCHFV suspected cases, healthcare workers, adult and hospitalized patients, ticks of the genus Ornithodoros and Amblyomma and in animals of the orders Perissodactyla and Bucerotiformes. This review highlights a significant disease burden due to CCHFV with a strong disparity according to country income levels, geographic regions, various human categories and tick and other animal species. Preventive measures in the light of these findings are expected.

Systematic review and meta-analysis of the epidemiology of Lassa virus in humans, rodents and other mammals in sub-Saharan Africa.

Accurate data on the Lassa virus (LASV) human case fatality rate (CFR) and the prevalence of LASV in humans, rodents and other mammals are needed for better planning of actions that will ultimately reduce the burden of LASV infection in sub-Saharan Africa. In this systematic review with meta-analysis, we searched PubMed, Scopus, Africa Journal Online, and African Index Medicus from 1969 to 2020 to obtain studies that reported enough data to calculate LASV infection CFR or prevalence. Study selection, data extraction, and risk of bias assessment were conducted independently. We extracted all measures of current, recent, and past infections with LASV. Prevalence and CFR estimates were pooled using a random-effect meta-analysis. Factors associated with CFR, prevalence, and sources of between-study heterogeneity were determined using subgroup and metaregression analyses. This review was registered with PROSPERO, CRD42020166465. We initially identified 1,399 records and finally retained 109 reports that contributed to 291 prevalence records from 25 countries. The overall CFR was 29.7% (22.3-37.5) in humans. Pooled prevalence of LASV infection was 8.7% (95% confidence interval: 6.8-10.8) in humans, 3.2% (1.9-4.6) in rodents, and 0.7% (0.0-2.3) in other mammals. Subgroup and metaregression analyses revealed a substantial statistical heterogeneity explained by higher prevalence in tissue organs, in case-control, in hospital outbreak, and surveys, in retrospective studies, in urban and hospital setting, in hospitalized patients, and in West African countries. This study suggests that LASV infections is an important cause of death in humans and that LASV are common in humans, rodents and other mammals in sub-Saharan Africa. These estimates highlight disparities between sub-regions, and population risk profiles. Western Africa, and specific key populations were identified as having higher LASV CFR and prevalence, hence, deserving more attention for cost-effective preventive interventions.