-
Travel Medicine and Infectious Disease 2024Ebola virus disease (Ebola) is highly pathogenic, transmissible, and often deadly, with debilitating consequences. Superspreading within a cluster is also possible. In... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ebola virus disease (Ebola) is highly pathogenic, transmissible, and often deadly, with debilitating consequences. Superspreading within a cluster is also possible. In this study, we aim to document Ebola basic reproduction number (R): the average number of new cases associated with an Ebola case in a completely susceptible population.
METHODS
We undertook a systematic review and meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published between 1976 and February 27, 2023. We also manually searched the reference lists of the reviewed studies to identify additional studies. We included studies that reported R during Ebola outbreaks in Africa. We excluded studies that reported only the effective reproduction number (R). Abstracting data from included studies was performed using a pilot-tested standard form. Two investigators reviewed the studies, extracted the data, and assessed quality. The pooled R was determined by a random-effects meta-analysis. R was stratified by country. We also estimated the theoretically required immunization coverage to reach herd-immunity using the formula of (1-1/R) × 100 %.
RESULTS
The search yielded 2042 studies. We included 53 studies from six African countries in the systematic review providing 97 Ebola mean R estimates. 27 (with 46 data points) studies were included in the meta-analysis. The overall pooled mean Ebola R was 1.95 (95 % CI 1.74-2.15), with high heterogeneity (I = 99.99 %; τ = 0.38; and p < 0.001) and evidence of small-study effects (Egger's statistics: Z = 4.67; p < 0.001). Mean Ebola R values ranged from 1.2 to 10.0 in Nigeria, 1.1 to 7 in Guinea, 1.14 to 8.33 in Sierra Leone, 1.13 to 5 in Liberia, 1.2 to 5.2 in DR Congo, 1.34 to 2.7 in Uganda, and from 1.40 to 2.55 for all West African countries combined. Pooled mean Ebola R was 9.38 (95 % CI 4.16-14.59) in Nigeria, 3.31 (95 % CI 2.30-4.32) in DR Congo, 2.0 (95 % CI 1.25-2.76) in Uganda, 1.83 (95 % CI 1.61-2.05) in Liberia, 1.73 (95 % CI 1.47-2.0) in Sierra Leonne, and 1.44 (95 % CI 1.29-1.60) in Guinea. In theory, 50 % of the population needs to be vaccinated to achieve herd immunity, assuming that Ebola vaccine would be 100 % effective.
CONCLUSIONS
Ebola R varies widely across countries. Ebola has a much wider R range than is often claimed (1.3-2.0). It is possible for an Ebola index case to infect more than two susceptible individuals.
Topics: Humans; Hemorrhagic Fever, Ebola; Ebolavirus; Basic Reproduction Number; Ebola Vaccines; Disease Outbreaks; Liberia; Nigeria
PubMed: 38181864
DOI: 10.1016/j.tmaid.2023.102685 -
Journal of Global Health Jan 2023Globally, the respiratory syncytial virus (RSV) is the most common etiologic agent of acute respiratory illnesses in children. However, its burden has not been well... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Globally, the respiratory syncytial virus (RSV) is the most common etiologic agent of acute respiratory illnesses in children. However, its burden has not been well addressed in developing countries. We aimed to estimate the molecular epidemiology of RSV in children less than 18 years of age with acute respiratory infections in Africa by conducting a systematic review and meta-analysis.
METHODS
We systematically searched PubMed, Scopus, CINAHL, and Global Index Medicus databases to identify studies published from January 1, 2002, to April 27, 2022, following the PRISMA 2020 guideline. We assessed the study quality using the Joanna Brigg's Institute (JBI) critical appraisal checklists. We conducted a qualitative synthesis by describing the characteristics of included studies and performed the quantitative synthesis with random effects model using STATA-14. We checked for heterogeneity with Q statistics, quantified by I, and determined the prediction interval. We performed subgroup analyses to explain the sources of heterogeneity and assessed publication biases by funnel plots augmented with Egger's test.
RESULTS
Eighty-eight studies with 105 139 participants were included in the review. The overall pooled prevalence of RSV in children <18 years of age was 23% (95% confidence interval (CI) = 20, 25%). Considerable heterogeneity was present across the included studies. The adjusted prediction interval was found to be 19%-27%. Heterogeneities were explained by subgroups analyses. The highest prevalence of RSV was found among inpatients, 28% (95% CI = 25, 31%) compared with inpatients/outpatients and outpatients, with statistically significant differences (P < 0.01). The RSV estimate was also highest among those with acute lower respiratory tract illnesses (ALRTIs), 28% (95% CI = 25, 31%) compared with acute upper respiratory tract illnesses (AURTIs) and both acute upper/lower respiratory manifestations, with statistically different prevalence (P < 0.01). RSV infection estimates in each sub-region of Africa were statistically different (P < 0.01). There were no statistically significant differences in RSV infections by designs, specimen types, and specimen conditions, despite them contributing to heterogeneity.
CONCLUSIONS
We found a high prevalence of RSV in pediatric populations with acute respiratory tract illnesses in Africa, highlighting that the prevention and control of RSV infections in children deserve more attention.
REGISTRATION
PROSPERO CRD42022327054.
Topics: Child; Humans; Infant; Molecular Epidemiology; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Africa; Respiratory Tract Infections
PubMed: 36637855
DOI: 10.7189/jogh.13.04001 -
Epidemics Jun 2021Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development...
BACKGROUND
Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development of RSV vaccines. Mathematical models of RSV will play an important role in assessing the relative value of these interventions. Our objectives were to provide an overview of the existing RSV modelling literature in LMIC and summarize available results on population-level effectiveness and cost-effectiveness.
METHODS
We searched MEDLINE from 2000 to 2020 for English language publications that employed a mathematical model of RSV calibrated to LMIC. Qualitative data were extracted on study and model characteristics. Quantitative data were collected on key model input assumptions and base case effectiveness and cost-effectiveness estimates for various immunization strategies.
FINDINGS
Of the 283 articles reviewed, 15 met inclusion criteria. Ten studies used modelling techniques to explore RSV transmission and/or natural history, while eight studies evaluated RSV vaccines and/or monoclonal antibodies, three of which included cost-effectiveness analyses. Six studies employed deterministic compartmental models, five studies employed individual transmission models, and four studies used different types of cohort models. Nearly every model was calibrated to at least one middle-income country, while four were calibrated to low-income countries.
INTERPRETATION
The mathematical modelling literature in LMIC has demonstrated the potential effectiveness of RSV vaccines and monoclonal antibodies. This review has demonstrated the importance of accounting for seasonality, social contact rates, immunity from prior infection and maternal antibody transfer. Future models should consider incorporating individual-level risk factors, subtype-specific effects, long-term sequelae of RSV infections, and out-of-hospital mortality.
Topics: Developing Countries; Humans; Models, Theoretical; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 33662812
DOI: 10.1016/j.epidem.2021.100444 -
The Lancet. Infectious Diseases Nov 2019Vaccinating infants with a first dose of measles-containing vaccine (MCV1) before 9 months of age in high-risk settings has the potential to reduce measles-related... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vaccinating infants with a first dose of measles-containing vaccine (MCV1) before 9 months of age in high-risk settings has the potential to reduce measles-related morbidity and mortality. However, there is concern that early vaccination might blunt the immune response to subsequent measles vaccine doses. We systematically reviewed the available evidence on the effect of MCV1 administration to infants younger than 9 months on their immune responses to subsequent MCV doses.
METHODS
For this systematic review and meta-analysis, we searched for randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We included studies reporting data on strength or duration of humoral and cellular immune responses, and on vaccine efficacy or vaccine effectiveness after two-dose or three-dose MCV schedules. Our outcome measures were proportion of seropositive infants, geometric mean titre, vaccine efficacy, vaccine effectiveness, antibody avidity index, and T-cell stimulation index. We used random-effects meta-analysis to derive pooled estimates of the outcomes, where appropriate. We assessed the methodological quality of included studies using Grading of Recommendation Assessment, Development and Evaluation (GRADE) guidelines.
FINDINGS
Our search retrieved 1156 records and 85 were excluded due to duplication. 1071 records were screened for eligibility, of which 351 were eligible for full-text screening and 21 were eligible for inclusion in the review. From 13 studies, the pooled proportion of infants seropositive after two MCV doses, with MCV1 administered before 9 months of age, was 98% (95% CI 96-99; I=79·8%, p<0·0001), which was not significantly different from seropositivity after a two-dose MCV schedule starting later (p=0·087). Only one of four studies found geometric mean titres after MCV2 administration to be significantly lower when MCV1 was administered before 9 months of age than at 9 months of age or later. There was insufficient evidence to determine an effect of age at MCV1 administration on antibody avidity. The pooled vaccine effectiveness estimate derived from two studies of a two-dose MCV schedule with MCV1 vaccination before 9 months of age was 95% (95% CI 89-100; I=12·6%, p=0·29). Seven studies reporting on measles virus-specific cellular immune responses found that T-cell responses and T-cell memory were sustained, irrespective of the age of MCV1 administration. Overall, the quality of evidence was moderate to very low.
INTERPRETATION
Our findings suggest that administering MCV1 to infants younger than 9 months followed by additional MCV doses results in high seropositivity, vaccine effectiveness, and T-cell responses, which are independent of the age at MCV1, supporting the vaccination of very young infants in high-risk settings. However, we also found some evidence that MCV1 administered to infants younger than 9 months resulted in lower antibody titres after one or two subsequent doses of MCV than when measles vaccination is started at age 9 months or older. The clinical and public-health relevance of this immunity blunting effect are uncertain.
FUNDING
WHO.
Topics: Age Factors; Antibodies, Viral; Female; Humans; Immunity, Cellular; Immunity, Humoral; Immunization Schedule; Infant; Male; Measles; Measles Vaccine; Measles virus; T-Lymphocytes; Treatment Outcome
PubMed: 31548081
DOI: 10.1016/S1473-3099(19)30396-2 -
PloS One 2021Viral outbreaks present a particular challenge in countries in Africa where there is already a high incidence of other infectious diseases, including malaria which can... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Viral outbreaks present a particular challenge in countries in Africa where there is already a high incidence of other infectious diseases, including malaria which can alter immune responses to secondary infection. Ebola virus disease (EVD) is one such problem; understanding how Plasmodium spp. and Ebolavirus (EBOV) interact is important for future outbreaks.
METHODS
We conducted a systematic review in PubMed and Web of Science to find peer-reviewed papers with primary data literature to determine 1) prevalence of EBOV/Plasmodium spp. coinfection, 2) effect of EBOV/Plasmodium spp. coinfection on EVD pathology and the immune response, 3) impact of EBOV/Plasmodium spp. coinfection on the outcome of EVD-related mortality. Random effects meta-analyses were conducted with the R package meta to produce overall proportion and effect estimates as well as measure between-study heterogeneity.
RESULTS
From 322 peer-reviewed papers, 17 were included in the qualitative review and nine were included in a meta-analysis. Prevalence of coinfection was between 19% and 72%. One study reported significantly lower coagulatory response biomarkers in coinfected cases but no difference in inflammatory markers. Case fatality rates were similar between EBOV(+)/Pl(+) and EBOV(+)/Pl(-) cases (62.8%, 95% CI 49.3-74.6 and 56.7%, 95% CI 53.2-60.1, respectively), and there was no significant difference in risk of mortality (RR 1.09, 95% CI 0.90-1.31) although heterogeneity between studies was high. One in vivo mouse model laboratory study found no difference in mortality by infection status, but another found prior acute Plasmodium yoeli infection was protective against morbidity and mortality via the IFN-γ signalling pathway.
CONCLUSION
The literature was inconclusive; studies varied widely and there was little attempt to adjust for confounding variables. Laboratory studies may present the best option to answer how pathogens interact within the body but improvement in data collection and analysis and in diagnostic methods would aid patient studies in the future.
Topics: Animals; Coinfection; Disease Outbreaks; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Malaria; Prevalence
PubMed: 34029352
DOI: 10.1371/journal.pone.0251101 -
BMC Infectious Diseases Oct 2022Respiratory syncytial virus (RSV) and influenza viruses are important global causes of morbidity and mortality. We evaluated the diagnostic accuracy of the Luminex NxTAG... (Meta-Analysis)
Meta-Analysis
Respiratory syncytial virus (RSV) and influenza viruses are important global causes of morbidity and mortality. We evaluated the diagnostic accuracy of the Luminex NxTAG respiratory pathogen panels (RPPs)™ (index) against other RPPs (comparator) for detection of RSV and influenza viruses. Studies comparing human clinical respiratory samples tested with the index and at least one comparator test were included. A random-effect latent class meta-analysis was performed to assess the specificity and sensitivity of the index test for RSV and influenza. Risk of bias was assessed using the QUADAS-2 tool and certainty of evidence using GRADE. Ten studies were included. For RSV, predicted sensitivity was 99% (95% credible interval [CrI] 96-100%) and specificity 100% (95% CrI 98-100%). For influenza A and B, predicted sensitivity was 97% (95% CrI 89-100) and 98% (95% CrI 88-100) respectively; specificity 100% (95% CrI 99-100) and 100% (95% CrI 99-100), respectively. Evidence was low certainty. Although index sensitivity and specificity were excellent, comparators' performance varied. Further research with clear patient recruitment strategies could ascertain performance across different populations.Protocol Registration: Prospero CRD42021272062.
Topics: Humans; Influenza A virus; Influenza B virus; Influenza, Human; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Sensitivity and Specificity
PubMed: 36229786
DOI: 10.1186/s12879-022-07766-9 -
The Lancet. Global Health Aug 2021Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global... (Meta-Analysis)
Meta-Analysis
Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis.
BACKGROUND
Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0-5 months, 6-11 months, and 12-59 months of age.
METHODS
We did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case-fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570).
FINDINGS
203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8-28·9) ALRI cases, 725 000 (433 000-1 260 000) ALRI hospital admissions, and 34 400 (16 400-73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0-5 months and 26% for 6-11 months) of the hospital admissions and 66% (42% for infants aged 0-5 months and 24% for 6-11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46-65% for the adjustment for health-care use, 59-77% for patient groups excluded, 54-93% for case definition, 42-93% for sampling strategy, and 67-77% for test methods. Heterogeneity in estimates was found between studies for each outcome.
INTERPRETATION
We report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4-14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Child, Preschool; Global Health; Humans; Infant; Infant, Newborn; Paramyxoviridae Infections; Paramyxovirinae; Respiratory Tract Infections
PubMed: 34166626
DOI: 10.1016/S2214-109X(21)00218-7 -
PLoS Neglected Tropical Diseases Oct 2020One of the leading challenges in the 2013-2016 West African Ebola virus disease (EVD) outbreak was how best to quickly identify patients with EVD, separating them from... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
One of the leading challenges in the 2013-2016 West African Ebola virus disease (EVD) outbreak was how best to quickly identify patients with EVD, separating them from those without the disease, in order to maximise limited isolation bed capacity and keep health systems functioning.
METHODOLOGY
We performed a systematic literature review to identify all published data on EVD clinical symptoms in adult patients. Data was dual extracted, and random effects meta-analysis performed for each symptom to identify symptoms with the greatest risk for EVD infection.
RESULTS
Symptoms usually presenting late in illness that were more than twice as likely to predict a diagnosis of Ebola, were confusion (pOR 3.04, 95% CI 2.18-4.23), conjunctivitis (2.90, 1.92-4.38), dysphagia (1.95, 1.13-3.35) and jaundice (1.86, 1.20-2.88). Early non-specific symptoms of diarrhoea (2.99, 2.00-4.48), fatigue (2.77, 1.59-4.81), vomiting (2.69, 1.76-4.10), fever (1.97, 1.10-4.52), muscle pain (1.65, 1.04-2.61), and cough (1.63, 1.24-2.14), were also strongly associated with EVD diagnosis.
CONCLUSIONS
The existing literature fails to provide a unified position on the symptoms most predictive of EVD, but highlights some early and late stage symptoms that in combination will be useful for future risk stratification. Confirmation of these findings across datasets (or ideally an aggregation of all individual patient data) will aid effective future clinical assessment, risk stratification tools and emergency epidemic response planning.
Topics: Adolescent; Adult; Diarrhea; Ebolavirus; Fatigue; Female; Fever; Hemorrhagic Fever, Ebola; Humans; Male; Middle Aged; Vomiting; Young Adult
PubMed: 33095771
DOI: 10.1371/journal.pntd.0008799 -
The Pediatric Infectious Disease Journal May 2024Acute lower respiratory infection (ALRI) caused by respiratory viruses is among the most common causes of hospitalization and mortality in children. We aimed to identify... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute lower respiratory infection (ALRI) caused by respiratory viruses is among the most common causes of hospitalization and mortality in children. We aimed to identify risk factors for poor outcomes in children <5 years old hospitalized with ALRI caused by respiratory syncytial virus (RSV), influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
METHODS
We searched Embase, Medline and Global Health databases and included observational studies reporting risk factors for poor outcomes (defined as use of supplemental oxygen, mechanical ventilation, intensive care unit admission, prolonged hospital stay and mortality) published between January 2011 and January 2023. Two authors independently extracted data on study characteristics, outcomes and risk factors. Due to limited data, meta-analyses were only conducted for RSV-ALRI poor outcome risk factors using random effects model when there were at least 3 studies.
RESULTS
We included 30 studies. For RSV-related ALRI, significant risk factors based on meta-analysis were: neurological disease [odds ratio (OR): 6.14; 95% confidence intervals (CIs): 2.39-15.77], Down's syndrome (5.43; 3.02-9.76), chronic lung disease (3.64; 1.31-10.09), immunocompromised status (3.41; 1.85-6.29), prematurity (2.98; 1.93-4.59), congenital heart disease (2.80; 1.84-4.24), underlying disease (2.45; 1.94-3.09), age <2 months (2.29; 1.78-2.94), age <6 months (2.08; 1.81-2.39), viral coinfection (2.01; 1.27-3.19), low birth weight (1.88; 1.19-2.95) and being underweight (1.80; 1.38-2.35). For influenza-related ALRI, chronic conditions and age 6-24 months were identified as risk factors for poor outcomes. Cardiovascular disease, immunosuppression, chronic kidney disease, diabetes and high blood pressure were reported as risk factors for mortality due to SARS-CoV-2 associated ALRI.
CONCLUSIONS
These findings might contribute to the development of guidelines for prophylaxis and management of ALRI caused by RSV, influenza and SARS-CoV-2.
Topics: Infant, Newborn; Child; Humans; Infant; Child, Preschool; Influenza, Human; Respiratory Tract Infections; Infant, Premature; Hospitalization; Risk Factors; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 38285519
DOI: 10.1097/INF.0000000000004258 -
International Journal of Infectious... Jan 2020The present study provides a comprehensive review of the recently published data on RSV epidemiology in adults and the elderly in Latin America. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The present study provides a comprehensive review of the recently published data on RSV epidemiology in adults and the elderly in Latin America.
METHODS
A systematic literature search was carried out in Medline, Scielo, Lilacs, and Cochrane Library. The search strategy aimed at retrieving studies focusing on RSV prevalence, burden, risk factors, and the routine clinical practice in the prevention and management of RSV infections in Latin American countries. Only articles published between January 2011 and December 2017 were considered.
RESULTS
Eighteen studies were included. Percentages of RSV detection varied highly across included studies for adult subjects with respiratory infections (0% to 77.9%), influenza-like illness (1.0% to 16.4%) and community-acquired pneumonia (1.3% to 13.5%). Considerable percentages of hospitalization were reported for RSV-infected adults with influenza-like illness (40.9% and 69.9%) and community-acquired pneumonia (91.7%).
CONCLUSIONS
Recent RSV data regarding adult populations in Latin America are scarce. RSV was documented as a cause of illness in adults and the elderly, being identified in patients with acute respiratory infections, influenza-like illness and community-acquired pneumonia. The studies suggest that RSV infections may be a significant cause of hospitalization in adult populations in Latin America, including younger adults.
Topics: Adult; Aged; Aged, 80 and over; Community-Acquired Infections; Female; Hospitalization; Humans; Latin America; Male; Middle Aged; Prevalence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Risk Factors; Young Adult
PubMed: 31669592
DOI: 10.1016/j.ijid.2019.10.025