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Journal of Neurology Mar 2024Case-reports/series and cohorts of Guillain-Barré syndrome (GBS) associated with COVID-19 vaccination have been reported. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Case-reports/series and cohorts of Guillain-Barré syndrome (GBS) associated with COVID-19 vaccination have been reported.
METHODS
A systematic review and meta-analysis of cohort studies of GBS after COVID-19 vaccination was carried out. Incidence and incidence rate ratio for a number of vaccine doses and risk of GBS, also considering the specific vaccine technology, were calculated in a random-effects model.
RESULTS
Of 554 citations retrieved, 518 were discarded as irrelevant. We finally included 15 studies. The random effect model yielded, regardless of the vaccine technology, 1.25 (95%CI 0.21; 2.83) GBS cases per million of COVID-19 vaccine doses, 3.93 (2.54; 5.54) cases per million doses for adenovirus-vectored vaccines and 0.69 (0.38; 1.06) cases per million doses for mRNA vaccines. The GBS risk was 2.6 times increased with the first dose. Regardless of the vaccine technology, the GBS risk was not increased but disaggregating the data it was 2.37 (1.67; 3.36) times increased for adenovirus-vectored vaccines and 0.32 (0.23; 0.47) for mRNA vaccines. Mortality for GBS after vaccination was 0.10 per million doses and 4.6 per GBS cases.
CONCLUSIONS
Adenovirus-vectored vaccines showed a 2.4 times increased risk of GBS that was about seven times higher compared with mRNA-based vaccines. The decreased GBS risk associated with mRNA vaccines was possibly due to an elicited reduction of infections, including SARS-CoV-2, associated with GBS during the vaccination period. How adenovirus-vectored COVID-19 vaccines may trigger GBS is unclear and further studies should investigate the relationship between vaccine technologies and GBS risk.
Topics: Humans; COVID-19; COVID-19 Vaccines; Guillain-Barre Syndrome; mRNA Vaccines; Vaccination
PubMed: 38233678
DOI: 10.1007/s00415-024-12186-7 -
Virology Journal Nov 2023The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation on the basis of preclinical trial reports.
METHODS
Publicly available databases (PubMed, Embase, Medline, Web of Science and Cochrane Library.) and register (Clinicaltrials.gov) were searched to collect treatment outcomes of oncolytic virotherapies (including herpes simplex virus type 1 (HSV), coxsackievirus A21 (CVA21), adenovirus, poxvirus and reovirus) for advanced/unresectable melanoma. Comparisons of treatment response, adverse events (AEs) and survival analyses for different virotherapies were performed by R software based on the extracted data from eligible studies.
RESULTS
Finally, thirty-four eligible studies were analysed and HSV virotherapy had the highest average complete response (CR, 24.8%) and HSV had a slightly higher average overall response rate (ORR) than CVA21 (43.8% vs 42.6%). In the pooled results of comparing talimogene laherparepve (T-VEC) with or without GM-CSF/ICIs (immune checkpoint inhibitors) to GM-CSF/ICIs monotherapy suggested virotherapy was more efficient in subgroups CR (RR = 1.80, 95% CI [1.30; 2.51], P < 0.01), ORR (RR = 1.17, 95% CI [1.02; 1.34], P < 0.05), and DCR (RR = 1.27, 95% CI [1.15; 1.40], P < 0.01). In patients treated with T-VEC+ICIs, 2-year overall survival (12.1 ± 6.9 months) and progression-free survival (9.9 ± 6.9) were significantly longer than those treated with T-VEC alone. Furthermore, we found that AEs occurred frequently in virotherapy but decreased in a large cohort of enrolled patients, some of which, such as abdominal distension/pain, injection site pain and pruritus, were found to be positively associated with disease progression in patients treated with T-VEC monotherapy.
CONCLUSION
Given the relative safety and tolerability of oncolytic viruses, and the lack of reports of dose-limiting-dependent toxicities, more patients treated with T-VEC with or without ICIs should be added to future assessment analyses. There is still a long way to go before it can be used as a first-line therapy for patients with advanced or unresectable melanoma.
Topics: Humans; Oncolytic Virotherapy; Granulocyte-Macrophage Colony-Stimulating Factor; Immunotherapy; Melanoma; Oncolytic Viruses; Pain
PubMed: 37919738
DOI: 10.1186/s12985-023-02220-x -
The Journal of Infection Jan 2024The sudden outbreak of severe acute hepatitis of unknown aetiology (SAHUA) in the first half of 2022 affected more than 1010 children in 35 countries worldwide. Dire... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The sudden outbreak of severe acute hepatitis of unknown aetiology (SAHUA) in the first half of 2022 affected more than 1010 children in 35 countries worldwide. Dire clinical outcomes, such as acute liver failure necessitating transplantation, neurological symptoms, long-term sequelae, and death, highlight the need to determine the pathogenesis of this condition. Hypotheses on the aetiology include adenovirus and SARS-CoV-2 infections and an aberrant immune response to multiple pathogen exposure following lifting of lockdown measures but further investigation is required to reach an informed consensus.
METHODS
A literature search was performed on MEDLINE and EMBASE in accordance with PRISMA guidelines for systematic reviews. Primary studies reporting data on severe acute hepatitis of unknown aetiology in children from the COVID-19 era were selected for inclusion in our review. Data on patient demographics, clinical presentation and outcomes, and diagnostic testing for coinfection were extracted. Meta-analysis used a random-effects model.
RESULTS
The 33 included studies (30 case series and 3 case-control studies) described a total of 3636 cases of SAHUA (reported 1 January, 2019-31 December, 2022), with a median age of 3.5 years. Of these, 214 children (5.9%) received a liver transplant and 66 (1.8%) died. Whilst data on diagnostic testing was incomplete, the most frequently detected coinfections were with adenovirus and/or adeno-associated virus 2 (AAV2). Other common childhood respiratory and enteric pathogens, such as enterovirus, rhinovirus, and herpesviruses (EBV and HHV-6), were also identified.
CONCLUSION
Coinfection with AAV2 and other common childhood pathogens may predispose children to develop this novel severe hepatitis. Altered susceptibility and response to such pathogens may be a consequence of immunological naivety following pandemic restrictions. Further investigations are needed to generate high-quality evidence on aetiology for different patient demographics and geographical areas.
Topics: Child; Humans; Child, Preschool; Coinfection; COVID-19; Disease Outbreaks; Pandemics; Hepatitis; Acute Disease
PubMed: 38007049
DOI: 10.1016/j.jinf.2023.11.011 -
Frontiers in Pediatrics 2023In April 2022, the World Health Organization (WHO) declared a global outbreak of acute hepatitis of unknown etiology (AHUE) with a high risk of severe outcomes, for... (Review)
Review
In April 2022, the World Health Organization (WHO) declared a global outbreak of acute hepatitis of unknown etiology (AHUE) with a high risk of severe outcomes, for which various etiologies have been proposed by the literature. This study examines primary reports of pediatric AHUE cases and summarizes the proposed etiologies. This systematic review collected and evaluated published peer-reviewed articles, official data, and clinical reports of AHUE cases that met the WHO working case definition. 19 hypothesized etiologies for AHUE were identified from 36 sources, which fell into eight categories. While human adenovirus (HAdV) infection, viral infection, and immune-mediated responses were commonly suspected as causes of AHUE, no definitive etiology or epidemiological link has been established. However, recent evidence implicates adeno-associated virus-2 (AAV2) as a likely significant contributor. Conducting a comprehensive literature review following outbreaks is necessary for developing responsive strategies and protocols.
PubMed: 38089685
DOI: 10.3389/fped.2023.1285348 -
The Lancet. Global Health Jun 2024Information on the causes of deaths from diarrhoea in children younger than 5 years is needed to design improved preventive and therapeutic approaches. We aimed to...
BACKGROUND
Information on the causes of deaths from diarrhoea in children younger than 5 years is needed to design improved preventive and therapeutic approaches. We aimed to conduct a systematic analysis of studies to report estimates of the causes of deaths from diarrhoea in children younger than 5 years at global and regional levels during 2000-21.
METHODS
For this systematic review and Bayesian multinomial analysis, we included 12 pathogens with the highest attributable incidence in the Global Enteric Multicenter Study. We searched PubMed, Scopus, Embase, Web of Science, Global Health Index Medicus, Global Health OVID, IndMed, Health Information Platform for the Americas (PLISA), Africa-Wide Information, and Cochrane Collaboration for articles published between Jan 1, 2000, and Dec 31, 2020, using the search terms "child", "hospital", "diarrhea", "diarrhoea", "dysentery", "rotavirus", "Escherichia coli", "salmonella", "shigella", "campylobacter", "Vibrio cholerae", "cryptosporidium", "norovirus", "astrovirus", "sapovirus", and "adenovirus". To be included, studies had to have a patient population of children younger than 5 years who were hospitalised for diarrhoea (at least 90% of study participants), at least a 12-month duration, reported prevalence in diarrhoeal stools of at least two of the 12 pathogens, all patients with diarrhoea being included at the study site or a systematic sample, at least 100 patients with diarrhoea, laboratory tests done on rectal swabs or stool samples, and standard laboratory methods (ie, quantitative PCR [qPCR] or non-qPCR). Studies published in any language were included. Studies were excluded if they were limited to nosocomial, chronic, antibiotic-associated, or outbreak diarrhoea or to a specific population (eg, only children with HIV or AIDS). Each article was independently reviewed by two researchers; a third arbitrated in case of disagreement. If both reviewers identified an exclusion criterion, the study was excluded. Data sought were summary estimates. Data on causes from published studies were adjusted when necessary to account for the poor sensitivity of non-qPCR methods and for attributable fraction based on quantification of pathogens in children who are ill or non-ill. The causes of deaths from diarrhoea were modelled on the causes of hospitalisations for diarrhoea. We separately modelled studies reporting causes of diarrhoea in children who were hospitalised in low-income and middle-income countries (LMICs) and in high-income countries (HICs).
FINDINGS
Of 74 282 papers identified in the initial database search, we included 138 studies (91 included data from LMICs and 47 included data from HICs) from 73 countries. We modelled estimates for 194 WHO member states (hereafter referred to as countries), including 42 HICs and 152 LMICs. We could attribute a cause to 1 003 448 (83·8%) of the estimated 1 197 044 global deaths from diarrhoea in children younger than 5 years in 2000 and 360 730 (81·3%) of the estimated 443 833 global deaths from diarrhoea in children younger than 5 years in 2021. The cause with the largest estimated global attribution was rotavirus; in LMICs, the proportion of deaths from diarrhoea due to rotavirus in children younger than 5 years appeared lower in 2021 (108 322 [24·4%] of 443 342, 95% uncertainty interval 21·6-29·5) than in 2000 (316 382 [26·5%] of 1 196 134, 25·7-28·5), but the 95% CIs overlapped. In 2000, the second largest estimated attribution was norovirus GII (95 817 [8·0%] of 1 196 134 in LMICs and 225 [24·7%] of 910 in HICs); in 2021, Shigella sp had the second largest estimated attribution in LMICs (36 082 [8·1%] of 443 342), but norovirus remained with the second largest estimated attribution in HICs (84 [17·1%] of 490).
INTERPRETATION
Our results indicate progress in the reduction of deaths from diarrhoea caused by 12 pathogens in children younger than 5 years in the past two decades. There is a need to increase efforts for prevention, including with rotavirus vaccine, and treatment to eliminate further deaths.
FUNDING
Bill & Melinda Gates Foundation via Johns Hopkins University and the University of Virginia.
Topics: Humans; Diarrhea; Bayes Theorem; Infant; Child, Preschool; Global Health; Cause of Death; Infant, Newborn
PubMed: 38648812
DOI: 10.1016/S2214-109X(24)00078-0 -
Epidemiologia (Basel, Switzerland) May 2024Respiratory diseases, including respiratory syncytial virus (RSV) infections, are common reasons for seeking healthcare among refugees and asylum seekers. A systematic... (Review)
Review
Respiratory diseases, including respiratory syncytial virus (RSV) infections, are common reasons for seeking healthcare among refugees and asylum seekers. A systematic review with meta-analysis was designed to appraise all the available evidence on RSV infections among individuals in refugee camps. Three medical databases (PubMed, Embase, and Scopus) as well as the preprint repository medRxiv.org were searched for eligible observational studies, and the collected cases were pooled in a random-effects meta-analysis model. Heterogeneity was assessed using the I statistics. Funnel plots and a regression analysis were calculated for analyzing reporting bias. Eventually, six studies were retrieved from three areas (Bangladesh, Thailand, and Kenya), with pooled estimates of 129.704 cases per 1000 samples (95% CI 66.393 to 237.986) for RSV compared to 110.287 per 1000 people for influenza A (95% CI 73.186 to 162.889), 136.398 cases per 1000 people (95% CI 84.510 to 212.741) for human adenovirus (HAdV), 69.553 per 1000 people (95% CI 49.802 to 96.343) for parainfluenzavirus (PIFV), and 60.338 per 1000 people (95% CI 31.933 to 111.109) for human metapneumovirus (hMPV). Using influenza A as a reference group, the risk for a positive specimen was greater for RSV (relative risk [RR] 1.514, 95% CI 1.396 to 1.641) and HAdV (RR 1.984, 95% CI 1.834 to 2.146) and lower for influenza B (RR 0.276, 95% CI: 0.239 to 0.319), PIFV (RR: 0.889, 95% CI 0.806 to 0.981), and hMPV (RR 0.594, 95% CI 0.534 to 0.662). In summary, high rates of RSV infections were documented among individuals sheltered in refugee camps, stressing the importance of specifically designed preventive strategies.
PubMed: 38920751
DOI: 10.3390/epidemiologia5020016 -
The Journal of Infection Jun 2024Gastroenteritis viruses are the leading etiologic agents of diarrhea in children worldwide. We present data from thirty-three (33) eligible studies published between... (Meta-Analysis)
Meta-Analysis Review
Gastroenteritis viruses are the leading etiologic agents of diarrhea in children worldwide. We present data from thirty-three (33) eligible studies published between 2003 and 2023 from African countries bearing the brunt of the virus-associated diarrheal mortality. Random effects meta-analysis with proportion, subgroups, and meta-regression analyses were employed. Overall, rotavirus with estimated pooled prevalence of 31.0 % (95 % CI 24.0-39.0) predominated in all primary care visits and hospitalizations, followed by norovirus, adenovirus, sapovirus, astrovirus, and aichivirus with pooled prevalence estimated at 15.0 % (95 % CI 12.0-20.0), 10 % (95 % CI 6-15), 4.0 % (95 % CI 2.0-6.0), 4 % (95 % CI 3-6), and 2.3 % (95 % CI 1-3), respectively. Predominant rotavirus genotype was G1P[8] (39 %), followed by G3P[8] (11.7 %), G9P[8] (8.7 %), and G2P[4] (7.1 %); although, unusual genotypes were also observed, including G3P[6] (2.7 %), G8P[6] (1.7 %), G1P[6] (1.5 %), G10P[8] (0.9 %), G8P[4] (0.5 %), and G4P[8] (0.4 %). The genogroup II norovirus predominated over the genogroup I-associated infections (84.6 %, 613/725 vs 14.9 %, 108/725), with the GII.4 (79.3 %) being the most prevalent circulating genotype. In conclusion, this review showed that rotavirus remains the leading driver of viral diarrhea requiring health care visits and hospitalization among under-five years children in Africa. Thus, improved rotavirus vaccination in the region and surveillance to determine the residual burden of rotavirus and the evolving trend of other enteric viruses are needed for effective control and management of cases.
Topics: Humans; Gastroenteritis; Child, Preschool; Infant; Africa; Prevalence; Diarrhea; Rotavirus; Infant, Newborn; Genotype; Virus Diseases; Rotavirus Infections; Viruses
PubMed: 38697269
DOI: 10.1016/j.jinf.2024.106169 -
Infectious Disease Reports Mar 2024Human Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infections. Usually associated with infants and children, an increasing amount of evidence... (Review)
Review
Human Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infections. Usually associated with infants and children, an increasing amount of evidence suggests that RSV can cause substantial morbidity and mortality in immunocompromised individuals, including recipients of bone marrow transplantation (BMT). The present systematic review was therefore designed in accordance with the PRISMA guidelines to collect available evidence about RSV infections in BMT recipients. Three medical databases (PubMed, Embase, and MedRxiv) were therefore searched for eligible observational studies published up to 30 September 2023 and collected cases were pooled in a random-effects model. Heterogeneity was assessed using I statistics. Reporting bias was assessed by means of funnel plots and regression analysis. Overall, 30 studies were retrieved, including 20,067 BMT cases and 821 RSV infection episodes. Of them, 351 were lower respiratory tract infections, and a total of 78 RSV-related deaths were collected. A pooled attack rate of 5.40% (95% confidence interval [95%CI] 3.81 to 7.60) was identified, with a corresponding incidence rate of 14.77 cases per 1000 person-years (95%CI 9.43 to 20.11), and a case fatality ratio (CFR) of 7.28% (95%CI 4.94 to 10.60). Attack rates were higher in adults (8.49%, 95%CI 5.16 to 13.67) than in children (4.79%, 95%CI 3.05 to 7.45), with similar CFR (5.99%, 95%CI 2.31 to 14.63 vs. 5.85%, 95%CI 3.35 to 10.02). By assuming RSV attack rates as a reference group, influenza (RR 0.518; 95%CI 0.446 to 0.601), adenovirus (RR 0.679, 95%CI 0.553 to 0.830), and human metapneumovirus (RR 0.536, 95%CI 0.438 to 0.655) were associated with a substantially reduced risk for developing corresponding respiratory infection. Despite the heterogeneous settings and the uneven proportion of adult and pediatric cases, our study has identified high attack rates and a substantial CFR of RSV in recipients of BMT, stressing the importance of specifically tailored preventive strategies and the need for effective treatment options.
PubMed: 38667752
DOI: 10.3390/idr16020026 -
Alternative Therapies in Health and... Apr 2024Cervical cancer remains a major health concern globally, and combined modality treatment often includes radiotherapy or concurrent chemoradiotherapy. Recently,...
Efficacy and Safety of Recombinant Human p53 Adenovirus Injection Combined with Radiotherapy or Concurrent Chemoradiotherapy in the Treatment of Cervical Cancer: A Systematic Review and Meta-analysis.
OBJECTIVE
Cervical cancer remains a major health concern globally, and combined modality treatment often includes radiotherapy or concurrent chemoradiotherapy. Recently, recombinant human adenovirus-p53 (rAd-p53) has been introduced as a promising agent in treatment of cervical cancer.
METHODS
We conducted a systematic review and meta-analysis following the PRISMA guidelines. RCTs were identified through electronic databases without limitations on time or language. The studies should include patients diagnosed with cervical cancer receiving either rAd-p53 combined with radiotherapy or concurrent chemoradiotherapy (RT/CRT) or RT/CRT alone. Primary outcome measures were complete response rate (CRR) and objective response rate (ORR), as defined by WHO's criteria for solid tumor therapeutic evaluation. Secondary outcome measures included adverse reaction incidence.
RESULTS
We included 9 RCTs in the analysis. Meta-analysis revealed that rAd-p53 combined with radiotherapy or concurrent chemoradiotherapy significantly improved the CRR [OR = 1.67, 95%CI (1.29, 2.16), P < .0001] and ORR [OR = 1.26, 95%CI (1.15,1.37), P < .001] compared to radiotherapy or concurrent chemoradiotherapy alone. The incidence of fever was higher in the combination therapy group [OR = 2.80, 95%CI (1.40, 5.62), P < .001], but no significant differences were observed in the incidence of other adverse reactions.
CONCLUSIONS
The combination of rAd-p53 with radiotherapy or concurrent chemoradiotherapy exhibits enhanced therapeutic efficacy in the treatment of cervical cancer without a significant increase in severe adverse reactions. However, multicenter, large-scale, randomized clinical trials are warranted for further validation.
PubMed: 38639607
DOI: No ID Found -
BMC Infectious Diseases May 2024Human adenoviruses (HAdVs) have always been suggested as one of the main causes of gastroenteritis in children. However, no comprehensive report on the global... (Meta-Analysis)
Meta-Analysis
PURPOSE
Human adenoviruses (HAdVs) have always been suggested as one of the main causes of gastroenteritis in children. However, no comprehensive report on the global epidemiology of these viruses in pediatric gastroenteritis is available.
METHODS
A systematic search was conducted to obtain published papers from 2003 to 2023 in three main databases PubMed, Scopus, and Web of Science.
RESULTS
The estimated global pooled prevalence of HAdV infection in children with gastroenteritis was 10% (95% CI: 9-11%), with a growing trend after 2010. The highest prevalence was observed in Africa (20%, 95% CI: 14-26%). The prevalence was higher in inpatients (11%; 95% CI: 8-13%) and patients aged 5 years old and younger (9%; 95% CI: 7-10%). However, no significant difference was observed between male and female patients (P = 0.63). The most prevalent species was found to be the species F (57%; 95% CI: 41-72%). The most common HAdVs observed in children with gastroenteritis were types 40/41, 38, and 2. Analysis of case-control studies showed an association between HAdV and gastroenteritis in children (OR: 2.28, 95% CI; 1.51-3.44).
CONCLUSION
This study provided valuable insights into the importance of HAdVs in children with gastroenteritis, especially in hospitalized and younger children. The results can be used in future preventive measurements and the development of effective vaccines.
Topics: Humans; Gastroenteritis; Adenoviruses, Human; Adenovirus Infections, Human; Child, Preschool; Child; Infant; Prevalence; Female; Male
PubMed: 38724898
DOI: 10.1186/s12879-024-09386-x