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.

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.