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Background: There is arguing evidence regarding the association between maternal infections during pregnancy and the risk of intellectual disability (ID) in children. This systematic review and meta-analysis are essential to determine and address inconsistent findings between maternal infections during pregnancy and the risk of ID in children., Methods: The MOOSE and PRISMA guidelines were followed to perform and report on this study. The Medline/PubMed, Web of Science, Embase, and Scopus databases were searched from inception up to March 15, 2023, to identify potentially eligible studies. Inclusion and exclusion criteria were applied, as well as the Newcastle-Ottawa Scale was used to assess the methodological quality of studies included. The included studies were divided into two types based on the participants: (1) ID-based studies, which involved children with ID as cases and healthy children as controls and evaluated maternal infection in these participants; (2) infection-based studies, which assessed the prevalence or incidence of ID in the follow-up of children with or without exposure to maternal infection. We used Random-effects models (REM) to estimate the overall pooled odds ratio (OR) and 95% confidence intervals (CIs). The between-studies heterogeneity was assessed with the χ2-based Q-test and I2 statistic. Subgroup and sensitivity analyses were applied to explore the source of heterogeneity and results consistency., Results: A total of eight studies including 1,375,662 participants (60,479 cases and 1,315,183 controls) met the eligibility criteria. The REM found that maternal infection significantly increased the risk of ID in children (OR, 1.33; 95% CI, 1.21-1.46; I2 = 64.6). Subgroup analysis showed a significant association for both infection-based (OR, 1.27; 95%CI, 1.15-1.40; I2 = 51.2) and ID-based (OR, 1.44; 95%CI, 1.19-1.74; I2 = 77.1) studies. Furthermore, subgroup analysis based on diagnostic criteria revealed a significant association when maternal infection or ID were diagnosed using ICD codes (OR, 1.33; 95% CI, 1.20-1.48; I2 = 75.8)., Conclusion: Our study suggests that maternal infection during pregnancy could be associated with an increased risk of ID in children. This finding is consistent across different types of studies and diagnostic criteria. However, due to the heterogeneity and limitations of the included studies, we recommend further longitudinal studies to confirm the causal relationship and the underlying mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rezaeinejad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The role of infectious agents, including Chlamydia pneumoniae (Cpn), in the development of multiple sclerosis (MS), is still a matter of major contention., Objective: This meta-analysis study aimed to assess the actual involvement of Cpn in MS development., Methods: We undertook a search of international scientific databases to identify eligible studies. We used a random-effects meta-analysis model (REM) to generate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Heterogeneity was calculated using the I 2 statistic. Sensitivity and subgroup analyses were applied to assess the effects of study characteristics and socio-demographic variables on the pooled OR., Results: We identified 37 studies comprising 51 datasets that satisfied the inclusion criteria. Considering diagnostic methods for Cpn, 26 and 25 datasets used PCR- and serological-based methods, respectively. In PCR-based datasets, REM showed a significant positive association between Cpn infection and the development of MS (OR, 5.29; 95% CI, 3.12-8.97), while a non-significant positive association was achieved in serological-based datasets (OR, 1.34; 95% CI, 0.88-2.03). In subgroup analyses on PCR-based datasets, results were significant for both CSF (OR, 5.70) and serum (OR, 4.84) samples; both healthy (OR, 16.11) and hospital-based (OR, 2.88) controls; and both moderate (OR, 5.14) and high (OR, 5.48) quality studies. In serological-based datasets, only those that used CSF samples yielded significant results (OR, 3.41)., Conclusions: Our findings verify the significant positive relationship between Cpn infection and MS. We advocate prospective cohort studies with lifelong follow-ups and also experimental studies to better understand the role of Cpn in MS development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The higher hospitalisation rates of those aged 0-19 years (referred to herein as 'children') observed since the emergence of the immune-evasive SARS-CoV-2 Omicron variant and subvariants, along with the persisting vaccination disparities highlighted a need for in-depth knowledge of SARS-CoV-2 sero-epidemiology in children. Here, we conducted this systematic review to assess SARS-CoV-2 seroprevalence and determinants in children worldwide., Methods: In this systematic review and meta-analysis study, we searched international and preprinted scientific databases from December 1, 2019 to July 10, 2022. Pooled seroprevalences were estimated according to World Health Organization (WHO) regions (at 95% confidence intervals, CIs) using random-effects meta-analyses. Associations with SARS-CoV-2 seroprevalence and sources of heterogeneity were investigated using sub-group and meta-regression analyses. The protocol used in this study has been registered in PROSPERO (CRD42022350833)., Findings: We included 247 studies involving 757,075 children from 70 countries. Seroprevalence estimates varied from 7.3% (5.8-9.1%) in the first wave of the COVID-19 pandemic to 37.6% (18.1-59.4%) in the fifth wave and 56.6% (52.8-60.5%) in the sixth wave. The highest seroprevalences in different pandemic waves were estimated for South-East Asia (17.9-81.8%) and African (17.2-66.1%) regions; while the lowest seroprevalence was estimated for the Western Pacific region (0.01-1.01%). Seroprevalence estimates were higher in children at older ages, in those living in underprivileged countries or regions, and in those of minority ethnic backgrounds., Interpretation: Our findings indicate that, by the end of 2021 and before the Omicron wave, around 50-70% of children globally were still susceptible to SARS-CoV-2 infection, clearly emphasising the need for more effective vaccines and better vaccination coverage among children and adolescents, particularly in developing countries and minority ethnic groups., Funding: None., Competing Interests: All authors declare no competing interests. Prof. Hotez is a co-inventor of a COVID-19 recombinant protein vaccine technology owned by Baylor College of Medicine (BCM) that was recently licensed by Baylor Ventures non-exclusively and with no patent restrictions to several companies committed to advance vaccines for low- and middle-income countries. These include Biological E (India–CORBEVAX) and BioFarma (Indonesia–INDOVAC), Incepta (Bangladesh). He has no involvement in license negotiations conducted by BCM. Similar to other research universities, a long-standing BCM policy provides its faculty and staff, who make discoveries and that result in a commercial license, a share of any royalty income. To date, BCM has not distributed any royalty income to the co-inventors on the COVID-19 recombinant protein vaccine technology., (© 2022 The Author(s).)

Background: There is considerable controversy around the question as to whether Helicobacter pylori (H. pylori) infection has a protective or causative role in the development of multiple sclerosis (MS). This study evaluated published information to assess the association between H. pylori infection and MS., Methods: We conducted a comprehensive systematic review of relevant observational studies in international databases. A random-effects model was used to calculate pooled odds ratio (OR) and 95% confidence interval (CI). I 2 statistic was used to assess the between-study heterogeneity. Subgroup and meta-regression analyses were applied to identify the source of heterogeneity., Results: In total, 22 studies (25 datasets) were eligible for the meta-analysis: 17 datasets had prevalence data and eight datasets had data on the mean titer of anti-H. pylori IgG. The pooled prevalence of H. pylori was 44.1% (908/2606) in the MS patients and 46.1% (1016/2200) in the controls, indicating a non-significant protective effect of H. pylori on MS (OR, 0.82; 95%CI, 0.58-1.17). In the subgroup analysis, studies that used ELISA yielded a significant protective association (OR, 0.59; 95%CI, 0.46-0.77), while a positive non-significant association (OR, 1.33; 95%CI, 0.83-2.15) was found from studies that used other serological methods; interestingly, a significant positive association (OR, 6.64; 95%CI, 2.40-13.76) was found from studies that used histological methods to detect H. pylori infection., Conclusions: Our findings do not support the hypothesis that H. pylori infection represents a protective factor against the development of MS; however, the results varied depending on the diagnostic method(s). Particularly, a significant positive association was identified when studies introduced results based on histological examination, suggesting that active H. pylori infection might be a risk factor for development of MS. Thus, further studies are needed utilizing accurate diagnostic methods to elucidate the association between active H. pylori infection and MS., (© 2022 John Wiley & Sons Ltd.)

Previous epidemiologic evidence suggests a protective effect of Toxoplasma gondii infection against multiple sclerosis (MS) development; however, inconsistent findings have been reported in this regard. Therefore, we performed an updated meta-analysis of observational studies to investigate the association of To. gondii infection with MS development. We searched all articles published in PubMed, Scopus, Embase and Web of Science databases as of 20 December 2021. A random effects meta-analysis model was used to generate the pooled OR at 95% CIs. The heterogeneity between studies was assessed using I2 and Cochran's Q statistics. Moreover, the likelihood of publication bias was determined by Egger's regression test. A total of 11 studies were eligible for meta-analysis, including 1172 MS cases and 1802 controls. Our findings indicated that 29.8% (95% CI 22.8 to 37.2%) of MS patients were seropositive for To. gondii infection, compared with 34.2% (95% CI 21.9 to 47.6%) of control subjects. The estimated pooled OR was 0.79 (95% CI 0.49 to 1.26), suggesting a non-significant negative association between To. gondii infection and MS development (p>0.05). The current study does not support the significant protective role of To. gondii infection on MS development. Our findings imply that further well-designed epidemiological and mechanistic studies are warranted to ascertain the possible association between To. gondii infection and MS and to exclude the potential confounders., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Brain tumors are among the most fatal cancers with substantial morbidity and mortality worldwide. Epidemiologic evidence suggests that infectious agents, especially, protozoan parasite Toxoplasma gondii could be a possible risk factor or contributor. Here, we performed a systematic review and meta-analysis to evaluate the possible association between T. gondii infection/exposure and risk of brain tumors., Methods: We searched the PubMed, Embase, Scopus, and Web of Science collection databases from inception through 1st of December 2021. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were generated using random effects models. We did the subgroup analysis according to tumor types. Statistical tests for heterogeneity and sensitivity analyses were applied., Results: A total of seven eligible studies comprising 2323 patients diagnosed with brain tumors and 5131 healthy controls were included in the meta-analysis. T. gondii infection/exposure prevalence was 24.2% (95%CI, 12.7%-41.2) in cases and 12.9% (95%CI, 7.0-22.6%) in control subjects. Pooled analysis showed an overall OR of 1.96 (95%CI, 1.37-2.80), indicating a significant increased risk of brain tumors associated with T. gondii infection/exposure. In subgroup analysis T. gondii infection/exposure was significantly associated with gliomas (OR: 1.64, 95%CI, 1.15-2.33), meningioma (OR: 2.30, 95%CI, 1.0-5.27) and other types of brain tumors (OR: 2.19, 95%CI, 1.02-4.71)., Conclusion: This study provides suggestive evidence for an association between T. gondii infection/exposure and brain tumors. Our findings should be further confirmed by well-designed cohort studies with strict control of confounders. Moreover, we suggest that future studies also focus on the effect of T. gondii infection/exposure to the types of brain tumors., (Copyright © 2022 Elsevier Ltd. All rights reserved.)