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Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination. This study was designed as a systematic review and meta-regression. We did a systematic review of preprint and peer-reviewed published article databases from June 17, 2021, to Dec 2, 2021. Randomised controlled trials of COVID-19 vaccine efficacy and observational studies of COVID-19 vaccine effectiveness were eligible. Studies with vaccine efficacy or effectiveness estimates at discrete time intervals of people who had received full vaccination and that met predefined screening criteria underwent full-text review. We used random-effects meta-regression to estimate the average change in vaccine efficacy or effectiveness 1–6 months after full vaccination. Of 13 744 studies screened, 310 underwent full-text review, and 18 studies were included (all studies were carried out before the omicron variant began to circulate widely). Risk of bias, established using the risk of bias 2 tool for randomised controlled trials or the risk of bias in non-randomised studies of interventions tool was low for three studies, moderate for eight studies, and serious for seven studies. We included 78 vaccine-specific vaccine efficacy or effectiveness evaluations (Pfizer–BioNTech-Comirnaty, n=38; Moderna-mRNA-1273, n=23; Janssen-Ad26.COV2.S, n=9; and AstraZeneca-Vaxzevria, n=8). On average, vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21·0 percentage points (95% CI 13·9–29·8) among people of all ages and 20·7 percentage points (10·2–36·6) among older people (as defined by each study, who were at least 50 years old). For symptomatic COVID-19 disease, vaccine efficacy or effectiveness decreased by 24·9 percentage points (95% CI 13·4–41·6) in people of all ages and 32·0 percentage points (11·0–69·0) in older people. For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1–15·4) in people of all ages and 9·5 percentage points (5·7–14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time. COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20–30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy. Coalition for Epidemic Preparedness Innovations.

The global surge in the omicron (B.1.1.529) variant has resulted in many individuals with hybrid immunity (immunity developed through a combination of SARS-CoV-2 infection and vaccination). We aimed to systematically review the magnitude and duration of the protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against infection and severe disease caused by the omicron variant. For this systematic review and meta-regression, we searched for cohort, cross-sectional, and case–control studies in MEDLINE, Embase, Web of Science, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, the WHO COVID-19 database, and Europe PubMed Central from Jan 1, 2020, to June 1, 2022, using keywords related to SARS-CoV-2, reinfection, protective effectiveness, previous infection, presence of antibodies, and hybrid immunity. The main outcomes were the protective effectiveness against reinfection and against hospital admission or severe disease of hybrid immunity, hybrid immunity relative to previous infection alone, hybrid immunity relative to previous vaccination alone, and hybrid immunity relative to hybrid immunity with fewer vaccine doses. Risk of bias was assessed with the Risk of Bias In Non-Randomized Studies of Interventions Tool. We used log-odds random-effects meta-regression to estimate the magnitude of protection at 1-month intervals. This study was registered with PROSPERO (CRD42022318605). 11 studies reporting the protective effectiveness of previous SARS-CoV-2 infection and 15 studies reporting the protective effectiveness of hybrid immunity were included. For previous infection, there were 97 estimates (27 with a moderate risk of bias and 70 with a serious risk of bias). The effectiveness of previous infection against hospital admission or severe disease was 74·6% (95% CI 63·1–83·5) at 12 months. The effectiveness of previous infection against reinfection waned to 24·7% (95% CI 16·4–35·5) at 12 months. For hybrid immunity, there were 153 estimates (78 with a moderate risk of bias and 75 with a serious risk of bias). The effectiveness of hybrid immunity against hospital admission or severe disease was 97·4% (95% CI 91·4–99·2) at 12 months with primary series vaccination and 95·3% (81·9–98·9) at 6 months with the first booster vaccination after the most recent infection or vaccination. Against reinfection, the effectiveness of hybrid immunity following primary series vaccination waned to 41·8% (95% CI 31·5–52·8) at 12 months, while the effectiveness of hybrid immunity following first booster vaccination waned to 46·5% (36·0–57·3) at 6 months. All estimates of protection waned within months against reinfection but remained high and sustained for hospital admission or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection, and as a result might be able to extend the period before booster vaccinations are needed compared to individuals who have never been infected. WHO COVID-19 Solidarity Response Fund and the Coalition for Epidemic Preparedness Innovations.

Outbreaks of mumps virus infection are occurring with increased frequency, especially on college campuses. In this report, the use of a third dose of the MMR vaccine was shown to significantly contribute to outbreak control.

Objectives To estimate the proportion RSV-positive among children aged < 5 years hospitalized with ARI in low- and middle-income countries (LMIC), where 97% of RSV mortality occurs. Methods We conducted a systematic literature search for studies conducted pre-COVID-19 and published 2010—2022 (PROSPERO registration CRD42022361351). We estimated the RSV percent positivity and 95% confidence interval (CI) using random-effects meta-analyses. We assessed heterogeneity in RSV percent positivity using subgroup analyses and univariable meta-regression models. We assessed the influence of study sample size in sensitivity analyses. Results Seventy-three studies conducted in 37 LMICs were included. The summary estimate of percent RSV-positive from the meta-analysis of children < 5 years hospitalized with ARI was 26.2% (95% CI: 24.3–28.3%), ranging from 18.9% (16.4–21.6%) among children 6– < 60 months to 41.3% (36.4–46.4%) among children 0– < 6 months. Only five studies included children aged < 2 months, but RSV positivity was high among this group (40.2% [35.8–44.7%]). Percent positivity stratified by WHO region ranged from 23.6% in the Africa and Southeast Asian regions to 37.5% in the European region. RSV positivity was similar across country income groups. Univariable meta-regression models indicated that there was significant heterogeneity in RSV percent positivity across subgroups defined by mid-year of the study period, WHO region, number of study sites, recruitment method, hospital type, and specimen type ( p  < 0.05). Conclusions RSV detection was high among children aged < 5 years hospitalized with ARI in LMICs across all WHO regions, especially among infants aged < 6 months, among whom RSV may account for almost up to one-half of all ARI hospital admissions. Recent WHO-recommended RSV immunization for all countries may protect young infants aged < 6 months against severe RSV disease.

Vaccine probe studies have emerged in the past 15 years as a useful way to characterise disease. By contrast, traditional studies of vaccines focus on defining the vaccine effectiveness or efficacy. The underlying basis for the vaccine probe approach is that the difference in disease burden between vaccinated and unvaccinated individuals can be ascribed to the vaccine-specific pathogen. Vaccine probe studies can increase understanding of a vaccine's public health value. For instance, even when a vaccine has a seemingly low efficacy, a high baseline disease incidence can lead to a large vaccine-preventable disease burden and thus that population-based vaccine introduction would be justified. So far, vaccines have been used as probes to characterise disease syndromes caused by Haemophilus influenzae type b, pneumococcus, rotavirus, and early infant influenza. However, vaccine probe studies have enormous potential and could be used more widely in epidemiology, for example, to define the vaccine-preventable burden of malaria, typhoid, paediatric influenza, and dengue, and to identify causal interactions between different pathogens.

In Kenya, detailed data on the age-specific burden of influenza and RSV are essential to inform use of limited vaccination and treatment resources. We analyzed surveillance data from August 2009 to July 2012 for hospitalized severe acute respiratory illness (SARI) and outpatient influenza-like illness (ILI) at two health facilities in western Kenya to estimate the burden of influenza and respiratory syncytial virus (RSV). Incidence rates were estimated by dividing the number of cases with laboratory-confirmed virus infections by the mid-year population. Rates were adjusted for healthcare-seeking behavior, and to account for patients who met the SARI/ILI case definitions but were not tested. The average annual incidence of influenza-associated SARI hospitalization per 1,000 persons was 2.7 (95% CI 1.8-3.9) among children <5 years and 0.3 (95% CI 0.2-0.4) among persons ≥5 years; for RSV-associated SARI hospitalization, it was 5.2 (95% CI 4.0-6.8) among children <5 years and 0.1 (95% CI 0.0-0.2) among persons ≥5 years. The incidence of influenza-associated medically-attended ILI per 1,000 was 24.0 (95% CI 16.6-34.7) among children <5 years and 3.8 (95% CI 2.6-5.7) among persons ≥5 years. The incidence of RSV-associated medically-attended ILI was 24.6 (95% CI 17.0-35.4) among children <5 years and 0.8 (95% CI 0.3-1.9) among persons ≥5 years. Influenza and RSV both exact an important burden in children. This highlights the possible value of influenza vaccines, and future RSV vaccines, for Kenyan children.

Few comprehensive data exist on disease incidence for specific etiologies of acute respiratory illness (ARI) in older children and adults in Africa. From March 1, 2007, to February 28, 2010, among a surveillance population of 21,420 persons >5 years old in rural western Kenya, we collected blood for culture and malaria smears, nasopharyngeal and oropharyngeal swabs for quantitative real-time PCR for ten viruses and three atypical bacteria, and urine for pneumococcal antigen testing on outpatients and inpatients meeting a ARI case definition (cough or difficulty breathing or chest pain and temperature >38.0 °C or oxygen saturation <90% or hospitalization). We also collected swabs from asymptomatic controls, from which we calculated pathogen-attributable fractions, adjusting for age, season, and HIV-status, in logistic regression. We calculated incidence by pathogen, adjusting for health-seeking for ARI and pathogen-attributable fractions. Among 3,406 ARI patients >5 years old (adjusted annual incidence 12.0 per 100 person-years), influenza A virus was the most common virus (22% overall; 11% inpatients, 27% outpatients) and Streptococcus pneumoniae was the most common bacteria (16% overall; 23% inpatients, 14% outpatients), yielding annual incidences of 2.6 and 1.7 episodes per 100 person-years, respectively. Influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human metapneumovirus were more prevalent in swabs among cases (22%, 6%, 8% and 5%, respectively) than controls. Adenovirus, parainfluenza viruses, rhinovirus/enterovirus, parechovirus, and Mycoplasma pneumoniae were not more prevalent among cases than controls. Pneumococcus and non-typhi Salmonella were more prevalent among HIV-infected adults, but prevalence of viruses was similar among HIV-infected and HIV-negative individuals. ARI incidence was highest during peak malaria season. Vaccination against influenza and pneumococcus (by potential herd immunity from childhood vaccination or of HIV-infected adults) might prevent much of the substantial ARI incidence among persons >5 years old in similar rural African settings.

Shigella is an important cause of diarrheal morbidity and mortality globally. Data on disease burden across age groups, in different epidemiologic settings, and over time are needed to guide preventive strategies. We examined shigellosis in two sites in Kenya over a 10-year period. We used data from the Population-Based Infectious Disease Surveillance (PBIDS) platform in a rural (Asembo, population ~35,000) and urban (Kibera, population ~23,000) setting. PBIDS participants presenting to surveillance clinics with diarrhea (≥3 loose stools in 24-hour period) had stool collected and cultured; Shigella isolates underwent antimicrobial susceptibility testing. We estimated incidence by dividing Shigella cases by person-years- observation, adjusting for the proportion of diarrhea cases with stool collected and for care-seeking outside surveillance clinics. From January 1, 2010 to December 31, 2019, we isolated Shigella from 23% and 15% of 2,017 and 4,074 stool specimens collected in Asembo and Kibera, respectively; S. flexneri accounted for 61% and 67%, respectively. In Asembo, the adjusted shigellosis incidence was 684/100,000; it was highest in ages 12-23 months (1,873/100,000) and ≥50 years (1,502/100,000). In Kibera, the adjusted incidence was 647/100,000, highest in ages 12-23 (2,828/100,000) and 24-59 months (936/100,000). Incidence declined significantly in Asembo (p = 0.009), but not in Kibera (p = 0.53). Overall, ≥ 97% of isolates were susceptible to ciprofloxacin and ceftriaxone. The shigellosis burden was greatest among young toddlers in both urban and rural areas and was high among older adults in the rural setting. Although resistance to first-line antibiotics was infrequent, continued susceptibility monitoring is warranted.

The global response to COVID-19 saw the most rapid and extensive vaccination rollout in history. Yet there were large disparities in the introduction, scale-up, and evaluation of programmes. To systematically quantify these disparities, we generate linkages across public datasets containing country- and territory-level income data, COVID-19 vaccination rates, and COVID-19 vaccine effectiveness (VE). Our results show that, compared with high-income countries, lower-income countries introduced vaccines later, were less likely to achieve key coverage milestones, and were slower to do so where these milestones were achieved. The literature on primary series COVID-19 VE has been dominated by studies of mRNA vaccines from high-income countries, with data for other vaccines and lower-income countries appearing later and in substantially lower quantities. For vaccines with available VE data across multiple income settings (BNT162b2, mRNA-1273, and ChAdOx1-S), our meta-regression highlights robust protection against severe COVID-19, with no significant differences in primary series VE according to country-level income status during the Delta and Omicron periods. Our findings demonstrate the strong protection conferred by COVID-19 vaccines across diverse populations. Nonetheless, our results quantify the stark disparities that pervaded each stage of COVID-19 vaccine implementation, and highlight evidence gaps related to products and platforms being used across much of the globe. The COVID-19 vaccine rollout saw large global disparities in the introduction, scale-up, and evaluation of immunisation programmes. Here, the authors systematically quantify these disparities through linkage of public data sources.

Characterizing infectious disease burden in Africa is important for prioritizing and targeting limited resources for curative and preventive services and monitoring the impact of interventions. From June 1, 2006 to May 31, 2008, we estimated rates of acute lower respiratory tract illness (ALRI), diarrhea and acute febrile illness (AFI) among >50,000 persons participating in population-based surveillance in impoverished, rural western Kenya (Asembo) and an informal settlement in Nairobi, Kenya (Kibera). Field workers visited households every two weeks, collecting recent illness information and performing limited exams. Participants could access free high-quality care in a designated referral clinic in each site. Incidence and longitudinal prevalence were calculated and compared using Poisson regression. INCIDENCE RATES RESULTING IN CLINIC VISITATION WERE THE FOLLOWING: ALRI--0.36 and 0.51 episodes per year for children <5 years and 0.067 and 0.026 for persons ≥ 5 years in Asembo and Kibera, respectively; diarrhea--0.40 and 0.71 episodes per year for children <5 years and 0.09 and 0.062 for persons ≥ 5 years in Asembo and Kibera, respectively; AFI--0.17 and 0.09 episodes per year for children <5 years and 0.03 and 0.015 for persons ≥ 5 years in Asembo and Kibera, respectively. Annually, based on household visits, children <5 years in Asembo and Kibera had 60 and 27 cough days, 10 and 8 diarrhea days, and 37 and 11 fever days, respectively. Household-based rates were higher than clinic rates for diarrhea and AFI, this difference being several-fold greater in the rural than urban site. Individuals in poor Kenyan communities still suffer from a high burden of infectious diseases, which likely hampers their development. Urban slum and rural disease incidence and clinic utilization are sufficiently disparate in Africa to warrant data from both settings for estimating burden and focusing interventions.