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Frontiers in Immunology 2023Evidence has demonstrated inferior humoral immune responses after SARS-CoV-2 vaccination in kidney transplant recipients compared to the general population. However,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence has demonstrated inferior humoral immune responses after SARS-CoV-2 vaccination in kidney transplant recipients compared to the general population. However, data on cellular immune responses in this population have not been established.
METHODS
We searched the MEDLINE, Scopus, and Cochrane databases and included studies reporting cellular immune response rates in kidney transplant recipients after receiving SARS-CoV-2 vaccines. Studies that reported factors associated with cellular immune responders or non-responders were also included (PROSPERO: CRD42022375544).
RESULTS
From a total of 1,494 articles searched, 53 articles were included in the meta-analysis. In all, 21 studies assessed cellular immune response by interferon-γ enzyme-linked immunosorbent spot (IFN-γ ELISPOT), 22 studies used interferon-γ release assay (IGRA), and 10 studies used flow cytometric analysis. The pooled response rate after two doses (standard regimen) and three doses of vaccination was 47.5% (95%CI 38.4-56.7%) and 69.1% (95%CI 56.3-80.6%) from IFN-γ ELISPOT, 25.8% (95%CI 19.7-32.4%) and 14.7% (95%CI 8.5-22.2%) from IGRA, and 73.7% (95%CI 55.2-88.8%) and 86.5% (95%CI 75.3-94.9%) from flow cytometry, respectively. Recipients with seroconversion were associated with a higher chance of having cellular immune response (OR 2.58; 95%CI 1.89-3.54). Cellular immune response in kidney transplant recipients was lower than in dialysis patients (OR 0.24; 95%CI 0.16-0.34) and the general population (OR 0.10; 95%CI 0.07-0.14). Age and immunosuppressants containing tacrolimus or corticosteroid were associated with inferior cellular immune response.
CONCLUSION
Cellular immune response after SARS-CoV-2 vaccination in kidney transplant recipients was lower than in dialysis patients and the general population. Age, tacrolimus, and corticosteroid were associated with poor response. Cellular immune response should also be prioritized in vaccination studies.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022375544.
Topics: Humans; COVID-19; COVID-19 Vaccines; Kidney Transplantation
PubMed: 37575225
DOI: 10.3389/fimmu.2023.1220148 -
Pathogens (Basel, Switzerland) Aug 2023Sub-Saharan Africa (SSA) carries the highest burden of high-risk human papillomavirus (HR-HPV) in the world, driven by, and together with, HIV infection. This systematic... (Review)
Review
BACKGROUND
Sub-Saharan Africa (SSA) carries the highest burden of high-risk human papillomavirus (HR-HPV) in the world, driven by, and together with, HIV infection. This systematic review aimed to identify HR-HPV genotypes and their associated factors among women in SSA.
METHODS
A systematic review and meta-analysis of studies conducted in SSA on HR-HPV was conducted. Standard electronic databases were searched. R software version 3.6.0 was used for meta-analysis, with < 0.05 considered statistically significant.
RESULTS
We included 28 articles with a total of 22,652 participants. The overall pooled prevalence of HR-HPV genotypes was 55.13%, albeit high heterogeneity between studies. The overall pooled prevalence of HR-HPV genotypes in HIV-positive individuals was 75.51%, compared to 52.97% in HIV-negatives (OR = 4.68 (0.71-30.76)). HPV 16 (18%), 35 (10.12%), 52 (9.98%), 18 (9.7%) and 45 (6.82%) genotypes were the most prevalent. Twelve studies identified the most frequently reported risk factors associated with HR-HPV, with HIV infection (66.66%), multiple sexual partners (41.66%) and young age (41.66%) being the most reported risk factors.
CONCLUSIONS
The combined prevalence of HR-HPV genotypes among women in general and HIV-infected women in particular remains high in SSA. The presence of several genotypes not covered by the vaccine is remarkable and suggests the need for revision of current vaccination policies to prevent HR-HPV infections.
PubMed: 37623992
DOI: 10.3390/pathogens12081032 -
EClinicalMedicine Feb 2023The 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...
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.
PubMed: 36590788
DOI: 10.1016/j.eclinm.2022.101786 -
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 -
EClinicalMedicine Oct 2022Vaccines have been demonstrated to protect against high-risk human papillomavirus infection (HPV), including HPV-16/18, and cervical lesions among HIV negative women....
BACKGROUND
Vaccines have been demonstrated to protect against high-risk human papillomavirus infection (HPV), including HPV-16/18, and cervical lesions among HIV negative women. However, their efficacy remains uncertain for people living with HIV (PLHIV).We systematically reviewed available evidence on HPV vaccine on immunological, virological, or other biological outcomes in PLHIV.
METHODS
We searched five electronic databases (PubMed, Medline and Embase, clinicaltrials.gov and the WHO clinical trial database) for longitudinal prospective studies reporting immunogenicity, virological, cytological, histological, clinical or safety endpoints following prophylactic HPV vaccination among PLHIV. We included studies published by February 11th, 2021. We summarized results, assessed study quality, and conducted meta-analysis and subgroup analyses, where possible.
FINDINGS
We identified 43 publications stemming from 18 independent studies ( =18), evaluating the quadrivalent ( =15), bivalent ( =4) and nonavalent ( =1) vaccines. A high proportion seroconverted for the HPV vaccine types. Pooled proportion seropositive by 28 weeks following 3 doses with the bivalent, quadrivalent, and nonavalent vaccines were 0.99 (95% confidence interval: 0.95-1.00, =1), 0.99 (0.98-1.00, =9), and 1.00 (0.99-1.00, =1) for HPV-16 and 0.99 (0.96-1.00, =1), 0.94 (0.91-0.96, =9), and 1.00 (0.99-1.00, =1) for HPV-18, respectively. Seropositivity remained high among people who received 3 doses despite some declines in antibody titers and lower seropositivity over time, especially for HPV-18, for the quadrivalent than the bivalent vaccine, and for HIV positive than negative individuals. Seropositivity for HPV-18 at 29-99 weeks among PLHIV was 0.72 (0.66-0.79, =8) and 0.96 (0.92-0.99, =2) after 3 doses of the quadrivalent and bivalent vaccine, respectively and 0.94 (0.90-0.98, =3) among HIV-negative historical controls. Evidence suggests that the seropositivity after vaccination declines over time but it can lasts at least 2-4 years. The vaccines were deemed safe among PLHIV with few serious adverse events. Evidence of HPV vaccine efficacy against acquisition of HPV infection and/or associated disease from the eight trials available was inconclusive due to the low quality.
INTERPRETATION
PLHIV have a robust and safe immune response to HPV vaccination. Antibody titers and seropositivity rates decline over time but remain high. The lack of a formal correlate of protection and efficacy results preclude definitive conclusions on the clinical benefits. Nevertheless, given the burden of HPV disease in PLHIV, although the protection may be shorter or less robust against HPV-18, the robust immune response suggests that PLHIV may benefit from receiving HPV vaccination after acquiring HIV. Better quality studies are needed to demonstrate the clinical efficacy among PLHIV.
FUNDING
World Health Organization. MRC Centre for Global Infectious Disease Analysis, Canadian Institutes of Health Research, UK Medical Research Council (MRC).
PubMed: 35936024
DOI: 10.1016/j.eclinm.2022.101585 -
Viruses Dec 2022Defective interfering particles (DIPs) are particles containing defective viral genomes (DVGs) generated during viral replication. DIPs have been found in various RNA... (Review)
Review
Defective interfering particles (DIPs) are particles containing defective viral genomes (DVGs) generated during viral replication. DIPs have been found in various RNA viruses, especially in influenza viruses. Evidence indicates that DIPs interfere with the replication and encapsulation of wild-type viruses, namely standard viruses (STVs) that contain full-length viral genomes. DIPs may also activate the innate immune response by stimulating interferon synthesis. In this review, the underlying generation mechanisms and characteristics of influenza virus DIPs are summarized. We also discuss the potential impact of DIPs on the immunogenicity of live attenuated influenza vaccines (LAIVs) and development of influenza vaccines based on NS1 gene-defective DIPs. Finally, we review the antiviral strategies based on influenza virus DIPs that have been used against both influenza virus and SARS-CoV-2. This review provides systematic insights into the theory and application of influenza virus DIPs.
Topics: Humans; Antiviral Agents; Influenza Vaccines; Defective Interfering Viruses; Defective Viruses; COVID-19; SARS-CoV-2; Orthomyxoviridae; Virus Replication
PubMed: 36560777
DOI: 10.3390/v14122773 -
PloS One 2020Data on the variation in the medical resource utilization rate of Human Respiratory Syncytial Virus (HRSV) infected children by gestational age have recently been made... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of health care resource utilization among preterm and term infants hospitalized with Human Respiratory Syncytial Virus infections: A systematic review and meta-analysis of retrospective cohort studies.
INTRODUCTION
Data on the variation in the medical resource utilization rate of Human Respiratory Syncytial Virus (HRSV) infected children by gestational age have recently been made available. This review aimed to determine whether prematurity is independently associated with the use of medical resources in hospitalized children for HRSV infections.
METHODS
We conducted this systematic review on cohort studies published on the medical resources use in preterm and full-term patients hospitalized for confirmed HRSV infections. We searched PubMed, Embase, and Global Index medicus for eligible studies. The standardized mean difference (SMD) and Risk Ratio (RR) with their 95% confidence intervals (95% CI) were estimated as summary statistics with random effects meta-analysis. The overall results were adjusted to the common confounders by stratified analyses.
RESULTS
A total of 14 articles (20 studies) were included. Compared to full-term, preterm hospitalized with HRSV infections had more frequent intensive care unit admission (RR = 2.6, 95% CI = 1.9-3.5), increased length of stay in hospital (SMD = 0.6, 95% CI = 0.5-0.8) and intensive care unit (SMD = 0.6, 95% CI = 0.4-0.8) and increased case fatality rate (RR = 6.9, 95% CI = 2.0-23.8). Mechanical ventilation utilization was more frequent in preterm children ≤ 2 years (RR = 15.5, 95% CI = 8.9-26.4) and those who did not receive prophylaxis against HRSV (RR = 15.9, 95% CI = 9.1-27.9)] than in full-term children. No differences were identified in the frequency of emergency department visits, oxygen utilization, and the age at the first HRSV episode between preterm and full-term infants.
CONCLUSIONS
Regardless of gestational age, preterm infants hospitalized for HRSV infections, especially those ≤ 2 years, have an increased frequency of use of health resources and poor outcomes compared to full-term infants. HRSV vaccine development programs for pregnant women should be accelerated.
CLINICAL TRIALS REGISTRATION
Review registration PROSPERO, CRD42019124375.
Topics: Child Health Services; Delivery of Health Care; Gestational Age; Hospitalization; Humans; Infant; Infant, Premature; Infant, Premature, Diseases; Patient Acceptance of Health Care; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Retrospective Studies
PubMed: 32084214
DOI: 10.1371/journal.pone.0229357 -
PharmacoEconomics May 2023Considerable evidence on the costs and cost-effectiveness of biomedical, non-surgical interventions to prevent human immunodeficiency virus (HIV) transmission has been...
BACKGROUND
Considerable evidence on the costs and cost-effectiveness of biomedical, non-surgical interventions to prevent human immunodeficiency virus (HIV) transmission has been generated over the last decade. This study aims to synthesize findings and identify remaining knowledge gaps to suggest future research priorities.
METHODS
A systematic literature review was carried out in August 2020 using the MEDLINE, Embase, Global Health and EconLit databases to retrieve economic evaluations and costing studies of oral pre-exposure prophylaxis (PrEP), injectable long-acting PrEP, vaginal microbicide rings and gels, HIV vaccines and broadly neutralizing antibodies. Studies reporting costs from the provider or societal perspective were included in the analysis. Those reporting on behavioural methods of prevention, condoms and surgical approaches (voluntary medical male circumcision) were excluded. The quality of reporting of the included studies was assessed using published checklists.
RESULTS
We identified 3007 citations, of which 87 studies were retained. Most were set in low- and middle-income countries (LMICs; n = 53) and focused on the costs and/or cost-effectiveness of oral PrEP regimens (n = 70). Model-based economic evaluations were the most frequent study design; only two trial-based cost-effectiveness analyses and nine costing studies were found. Less than half of the studies provided practical details on how the intervention would be delivered by the health system, and only three of these, all in LMICs, explicitly focused on service integration and its implication for delivery costs. 'Real-world' programme delivery mechanisms and costs of intervention delivery were rarely considered. PrEP technologies were generally found to be cost-effective only when targeting high-risk subpopulations. Single-dose HIV vaccines are expected to be cost-effective for all groups despite substantial uncertainty around pricing.
CONCLUSIONS
A lack of primary, detailed and updated cost data, including above-service level costs, from a variety of settings makes it difficult to evaluate the cost-effectiveness of specific delivery modes at scale, or to evaluate strategies for services integration. Closing this evidence gap around real-world implementation is vital, not least because the strategies targeting high-risk groups that are recommended by PrEP models may incur substantially higher costs and be of limited practical feasibility in some settings.
Topics: Female; Humans; Male; Cost-Benefit Analysis; HIV; HIV Infections; AIDS Vaccines; Cost-Effectiveness Analysis
PubMed: 36529838
DOI: 10.1007/s40273-022-01223-w -
BMC Infectious Diseases Aug 2019HIV-infected children are at a higher risk of Invasive Pneumococcal Disease (IPD) and its mortality, even in the era of antiretroviral therapy. Therefore, an effective... (Meta-Analysis)
Meta-Analysis
Effectiveness of pneumococcal conjugate vaccination against invasive pneumococcal disease among children with and those without HIV infection: a systematic review and meta-analysis.
BACKGROUND
HIV-infected children are at a higher risk of Invasive Pneumococcal Disease (IPD) and its mortality, even in the era of antiretroviral therapy. Therefore, an effective vaccination strategy would be beneficial. To investigate the effectiveness of Pneumococcal Conjugate Vaccination (PCV) against IPD among HIV-Infected and HIV-Uninfected Children through a systematic review and meta-analysis.
METHODS
Observational studies and randomized trials on 7 years old or older children were searched in the Cochrane Library, Web of Science core collection, Embase, Medline/PubMed, and Google Scholar. Critical appraisal was done using the Cochrane risk of bias tool and the Newcastle-Ottawa quality assessment form. Effectiveness and efficacy of at least one dose of PCV was investigated among children with and without HIV considering subgroups of pneumococcal serotypes. We meta-analyzed the effect sizes using random-effects modeling.
RESULTS
Efficacy of PCV was estimated as 45.0% (31.2, 56.1) and 52.6% (25.7, 69.8) among HIV-infected and HIV-uninfected children, respectively. Effectiveness of PCV among HIV-infected children as - 6.2% (- 67.6, 32.7) was significantly lower than HIV-uninfected children 65.1% (47.3, 76.9). Effectiveness of PCV among HIV-infected children for IPDs caused by vaccine serotypes was estimated as 7.7(- 66.7, 48.9), and for IPDs caused by non-vaccine serotypes was estimated as - 402.8(- 1856, - 29.2).
CONCLUSION
Unlike the evidence on the efficacy of PCV against IPD among both of HIV-infected and HIV-uninfected children, its effectiveness against IPD among HIV-infected children is much less limited.
REVIEW REGISTRATION
The study protocol was registered at PROSPERO (registration ID: CRD42018108187).
Topics: AIDS-Related Opportunistic Infections; Child; Child, Preschool; Humans; Infant; Observational Studies as Topic; Pneumococcal Infections; Pneumococcal Vaccines; Randomized Controlled Trials as Topic; Vaccination; Vaccines, Conjugate
PubMed: 31382917
DOI: 10.1186/s12879-019-4325-4 -
International Journal of Medical... Jan 2021Orientia tsutsugamushi (OT), the causative agent of the vector-borne Scrub typhus zoonotic disease in humans, is a unique microorganism that exists in the Asia-Pacific...
Orientia tsutsugamushi (OT), the causative agent of the vector-borne Scrub typhus zoonotic disease in humans, is a unique microorganism that exists in the Asia-Pacific region since a long time. In spite of its occurrence, the organism had been neglected until recent years. Humans are the accidental dead-end hosts of O. tsutsugamushi and display manifestations which are both severe and misleading. The vast antigenic diversity of OT and non-pathognomic symptoms of Scrub typhus, create hurdles in the clinical management of the disease and impede the OT-research. Many countries in the Asia-Pacific region have reported the resurgence of OT- infections and have raised concerns for its expanding distribution. This has triggered the development of advanced techniques for diagnosis and research on exploring a successful vaccine candidate to reduce the burden of the disease. Thus, the aim of this systematic review is to provide an update on the recent advances in the OT-research and highlight the key areas that have remained obscure and demand attention.
Topics: Antigenic Variation; Asia; Humans; Orientia tsutsugamushi; Scrub Typhus
PubMed: 33338890
DOI: 10.1016/j.ijmm.2020.151467