Background A 10-valent Pneumococcal Conjugate Vaccine (PCV10 Synflorix) was introduced in Kenya in 2011 but the long-term impact of PCV10 in Africa is unknown. We evaluated PCV10 impact over 12 years in Kilifi, Kenya. Methods Surveillance for Invasive Pneumococcal Disease (IPD) was conducted among residents of the Kilifi Health and Demographic Surveillance System. We estimated the trend of IPD incidence during the post-vaccine period and used age- and serotype-group-specific rate ratios, adjusted for pre-defined confounders (surveillance year for children aged <5 years and proportion investigated among patients with an indication for blood culture), to compare IPD incidence in the post-vs pre-vaccine period. Findings Three-dose coverage of PCV10 among children aged 12–23 months varied from 79.2% to 94.6% annually. There were no significant trends in IPD incidence in the post-vaccine period (all p-values >0.05). Among children aged <5 years, IPD incidence (all serotypes) was 12.7 per 100,000 in the post-vaccine period (2012–2022), significantly lower than in the pre-vaccine period (1999–2010) (adjusted incidence rate ratio [IRR] 0.32; 95% CI 0.18–0.58). It also declined among children aged 5–14 years (aIRR 0.42; 95% CI 0.23–0.77) and persons aged ≥15 years (aIRR 0.62; 95% CI 0.35–1.10). The incidence of vaccine serotype (VT) IPD declined in persons aged <5 years (aIRR 0.09; 95% CI 0.03–0.21), 5–14 years (aIRR 0.20; 95% CI 0.09–0.45) and ≥15 years (aIRR 0.17; 95% CI 0.06–0.45). Among children aged <5 years in the post-vaccine period, 25%, 29%, and 39% of IPD was caused, respectively, by the additional serotypes included in Pneumosil, PCV13/15 and PCV20. Interpretation A wide-ranging catch-up campaign at PCV10 introduction accelerated reductions in VT-IPD incidence which were sustained over the long-term using a three-dose with no booster (3 + 0) infant schedule. There was a considerable residual burden of IPD of which only a minority is covered by currently available higher-valency PCVs, underscoring the need for effective vaccines with greater coverage. Ongoing, high-quality IPD surveillance will be essential to inform future policy deliberations on optimizing the cost-efficiency and impact of the PCV program. Funding Gavi, the Vaccine Alliance (EPIDZO76/M&E73201018) and the Wellcome Trust (203077/Z/16/Z).

Serosurveillance for vaccine-preventable diseases (VPDs) can inform public health strategies by identifying gaps in immunization programs. However, venous blood sampling, though reliable and sensitive for serosurveillance, presents logistical challenges in resource-limited settings. Capillary microsampling using dried blood spots (DBS) offers a simpler, less invasive alternative that reduces cold-chain and personnel requirements. This study evaluated the performance and stability of DBS collected on filter paper and Mitra microsamplers compared with venous plasma. IgG antibody levels against diphtheria, tetanus, pertussis, measles, mumps, rubella, and varicella were quantified using a validated fluorescent bead-based multiplex immunoassay. At baseline, strong agreement was observed between DBS and plasma, with ≥ 93% of observations within the 95% limits of agreement. Sensitivity was high (≥ 95.8%) for all pathogens except pertussis (72.2-77.8%). For DBS stored at - 20 °C with desiccants, agreement remained high at 90 days, with gradual declines observed beyond one year. At room temperature, IgG levels declined, with sensitivity ≥ 91.2% at 7 and 30 days but dropping below 90% by 90 days for several analytes. Beyond one year, IgG recovery was minimal, with sensitivity < 50% for most pathogens. These findings support DBS utility for VPD serosurveillance, with stability up to 90 days at - 20 °C and 30 days at room temperature.

BACKGROUND:Mass azithromycin distribution reduces child mortality in some settings, potentially through reductions in nasopharyngeal carriage of Streptococcus pneumoniae, but has been associated with increased antimicrobial resistance. Individual-level data are lacking on the impact of azithromycin on antimicrobial resistance over time. METHODS:We analyzed data from a double-blind, randomized placebo-controlled trial (ClinicalTrials.gov; NCT02414399) which followed 1398 hospitalized Kenyan children to evaluate the impact of a 5-day course of oral azithromycin at discharge from hospital on pneumococcal carriage and the proportion of isolates (among a random sample) resistant to azithromycin. Randomization to azithromycin or placebo (1:1) was stratified by enrollment county (Kisii or Homa Bay). Using generalized estimating equations, we calculated prevalence ratios (PRs) and 95% CIs for the intervention, adjusting for enrollment site. RESULTS:Overall, 1253/1398 (89.6%) enrolled children received antibiotics during their hospitalization. Pneumococcal carriage at discharge was similar among children randomized to the azithromycin group (158/702 [22.5%]) compared with the placebo group (171/696 [24.6%]; P = .4) and did not differ at month 3 (65.6% versus 67.0%; PR: 0.98 [0.90, 1.06]) or month 6 (66.7% versus 66.5%; PR: 1.00 [0.92, 1.08]). At discharge, 15.7% of isolates were resistant to azithromycin and there was no difference between azithromycin-treated and placebo groups at month 3 (35/266 [13.2%] versus 32/256 [12.5%]; PR: 1.06 [0.86, 1.66]) or month 6 (41/245 [16.7%] versus 43/243 [17.6%]; PR: 1.01 [0.69, 1.49]). CONCLUSIONS:Azithromycin treatment did not effect pneumococcal carriage or antimicrobial resistance 3- or 6-months post-randomization. High inpatient antibiotic use in this recently discharged population may have reduced any further impact of azithromycin.

There is limited epidemiologic data on varicella zoster virus (VZV) infections from low- and middle-income countries including Kenya. We aimed to describe the seroepidemiology of VZV in Kilifi, Kenya, where varicella vaccine is not included in the national infant immunization program, in order to generate evidence to inform vaccine policy. We conducted a retrospective serosurvey utilizing archived plasma and serum samples from cross-sectional population-based serosurveys conducted within the Kilifi Health and Demographic Surveillance System between 2009 and 2021. We assayed immunoglobulin G (IgG) for VZV using a validated Luminex multiplex immunoassay and applied a seropositivity cutoff of ≥0.26 International Units per millilitre (IU/mL), as determined by the assay developer. We calculated Bayesian-adjusted age-specific seroprevalence and tested differences in seroprevalence between groups using Chi square. We used a multivariable logistic regression model to estimate associations with VZV IgG antibody seropositivity. We fitted an age-dependent catalytic model to estimate the force of infection (FOI) in children aged 0.5-4, 5-9 and 10-14 years. A total of 2639 samples from children aged <15 years and 546 samples from persons aged ≥15 years were tested. The overall population-weighted seroprevalence of VZV IgG antibodies among children aged 0-14 years was 38.4% (95% CI 27.5-49.5). Age-specific seroprevalence rose from 13.3% (95% CI 5.8-21.6) in children aged 0-4 years to 60.9% (95% CI 45.0-76.2) in those aged 10-14 years. Survey year and age were associated with VZV IgG antibody seropositivity. Children aged 5-9 years had the highest FOI (0.098; 95% CI 0.077-0.120) per susceptible year while mean age of infection was 24.3 years (95% CrI 17.6-30.1). Approximately 40% of individuals entering adulthood in Kenya remain susceptible to VZV infection, suggesting a substantial and underappreciated risk of severe VZV disease in older population including pregnant women. An infant varicella immunization program might avert disease across both paediatric and adult populations.

OBJECTIVES:In Kilifi, pentavalent coverage remains below the 90% target, with no reported diphtheria or tetanus cases and sporadic pertussis. However, absence of disease does not guarantee immunity. To characterize age-specific gaps and waning protection not captured by routine surveillance, we conducted serial seroprevalence studies of diphtheria, pertussis, and tetanus. METHODS:We analyzed randomly selected participants from multiple cross-sectional surveys within the Kilifi Health and Demographic Surveillance System. Immunoglobulin G antibodies were measured using a fluorescent bead-based multiplex immunoassay applying protective thresholds ≥0.011 IU/ml for diphtheria and tetanus. Pertussis antibodies were grouped by time since infection. Bayesian multilevel regression with post-stratification adjusted estimates for population structure and assay performance; associations with age and year were assessed using logistic regression. RESULTS:Diphtheria seroprotection was low; only 5% of children had long-term seroprotection, with full protection ranging from 11% to 34% and minimal seroprotection from 40% to 52%. Minimal seroprotection increased over time (τ = 0.68, P = 0.04). Tetanus protection was higher, with long-term seroprotection ranging from 10% to 39% and susceptibility <1%; trends were not significant. Older age was associated with lower seroprevalence. Among adults, <1% had long-term diphtheria seroprotection vs 36% for tetanus. Pertussis circulation was minimal, with 5% of children and <1% of adults, with antibody concentrations consistent with recent infection. CONCLUSIONS:Although conventional serological thresholds suggest immunity gaps, particularly, for diphtheria, no diphtheria or tetanus outbreaks have occurred in Kilifi over the past decade. This indicates that antibody concentrations below standard thresholds may not equate to immediate susceptibility, but they do reflect a narrower margin of population immunity. Although this has not yet translated into disease, it could become relevant if transmission conditions change, underscoring the need to sustain high vaccination coverage and sensitive surveillance. Serology should, therefore, be viewed as a complementary tool, useful for tracking emerging vulnerability and informing future booster decisions if susceptibility increases.

BACKGROUND:Measles and rubella have been targeted for elimination by the World Health Organization. Age-specific population immunity to measles and rubella is important to assess progress towards elimination but data are scarce. We conducted seroprevalence surveys to identify disease-specific population immunity profiles in children and adults in Kilifi. METHODS:Sera from cross-sectional surveys in the Kilifi Health Demographic Surveillance System (2009-2021) were analysed using a fluorescent bead-based multiplex immunoassay. Bayesian multilevel regression with post stratification was used to obtain seroprevalence estimates adjusted for the underlying population and assay performance. Associations between seropositivity and age, sex, location and ethnic group were assessed using a mixed effects logistic regression. RESULTS:Measles-adjusted seroprevalence showed a significant increase from 88 % in 2009 to 93 % in 2021 (τ = 0.875, P = 0.01). Seropositivity was significantly higher in all age groups compared to those under 9 months. Seroprevalence among children ineligible for the first measles vaccine dose (MCV1) remained low (10-57 %), whereas MCV1-eligible children (9-17 months) had higher seroprevalence (68-91 %). Adult measles seroprevalence exceeded 96 %. Rubella seroprevalence followed a similar pattern, with adults above 88 %. Following the MR campaign, measles seroprevalence increased from 92 % to 96 % in eligible children, while rubella seroprevalence rose from 45 % to 82 %. CONCLUSION:Population immunity for measles significantly increased over the 12-year period suggesting improvement in immunisation program performance. To reduce reliance on frequent SIAs, efforts should focus on optimizing both the timing and coverage of routine doses, particularly ensuring higher coverage of MCV2. The introduction of rubella vaccination has positively impacted immunity in children. Sustaining this immunity is essential to prevent potential gaps in older age groups, which could increase the risk of Congenital Rubella Syndrome (CRS) in infants.

The Kenya Multi Site Serosurveillance (KEMIS) collaboration set out to implement an integrated, nationally representative, population-based program of serological surveillance for past infection for a number of important infectious diseases in Kenya. The project started in December 2021 and built on a portfolio of SARS-CoV-2 research conducted in 2020 and 2021. In this profile paper, we describe the background of the KEMIS collaboration, its aim and objectives, the Health and Demographic Surveillance System sites that were involved in data collection, and the key activities undertaken. We also explain how we established governance and management of the KEMIS collaboration, and reflect on opportunities, challenges, lessons learned, and future directions.

BackgroundMeasles outbreaks continue to cause a large burden of disease in Africa including Kenya. We used information from regular serological surveys in Kilifi Health and Demographic Surveillance System (KHDSS) in combination with mathematical modelling to estimate the relative contribution of the vaccination programme to current measles immunity.MethodsWe developed a static birth cohort model to track the proportion of children who are either measles naïve or seroconverted due to natural infection or vaccination through first dose of measles-containing vaccine (MCV1), the second dose (MCV2), or supplementary immunisation activities (SIAs). We fitted the model to biennial paediatric serological survey and case notification data and used vaccination coverage estimates from the KHDSS to estimate the relative contributions of vaccination and infection to measles immunity in Kilifi.ResultsWe estimated that between 2009 and 2021, 60% (95%CI 55-64%) of measles seroconversion in Kilifi was attributable to MCV1, with MCV2 contributing 1.0% (95%CI 0.9-1.1%) since its introduction. Natural infection and SIAs accounted for 24% (95%CI 17-31%) and 16% (95%CI 14-19%), respectively. A hypothetical 10% increase in MCV1 coverage increased the seroconversion attributed to MCV1 to 67% (95%CI 63-71%), with concurrent reductions in seroconversion from natural infection and SIAs to 13% (95%CI 9-18%) and 10% (95%CI 9-12%), respectively. Importantly, this same 10% increase in MCV1, if administered promptly at 9 months, could potentially reduce seroconversion from natural infection further from 24% to 11% (95%CI 07-15%) and reliance on SIAs from 16% to 8% (95% CI 7-10%).ConclusionOptimizing routine coverage timing and uptake is crucial for reducing SIAs dependence and measles susceptibility. A 10% MCV1 coverage increase could have halved susceptibility and lessened SIA demand, highlighting the potential of minor improvements in coverage to alleviate measles and reduce costly SIAs.

Background: A substantial fraction of the population-level impact of Pneumococcal Conjugate Vaccines (PCVs) on Invasive Pneumococcal Disease (IPD) is mediated through indirect effects, i.e., their capacity to protect against carriage acquisition of vaccine serotypes (VTs) among vaccinees, thereby proportionately reducing transmission and indirectly averting invasive disease in the whole population. Therefore, by relying on the consequent near elimination of VT carriage, early carriage-based models successfully captured the impact of seven-valent PCV (PCV7) in high-income settings. We sought to determine the applicability of three published statistical carriage-based models for the evaluation of PCV10 impact in Nigeria, where carriage prevalence data are available from urban and rural sites. Methods: We applied external data, with assumptions, to empirical carriage prevalence data to predict IPD incidence rate ratios (IRRs). The models assume PCV has no effect on serotype invasiveness among carriers because VT carriage is eliminated. Model 1 uses estimates of relative proportions of pre-PCV VT-IPD to predict IRRs. Model 2 uses pre-PCV serotype IPD incidence, while Model 3 uses measures of serotype invasiveness, the case-carrier ratio (CCR). Results: Model 1 estimates the largest PCV10 impact on overall IPD (IRR:0.38 and 0.50) in the urban and rural sites, respectively. Whereas estimates from Model 2 (IRR:0.69 and 0.78) and Model 3 (IRR:0.63 and 0.70) were more conservative. Conclusions: VT carriage was not eliminated in our setting, so Model 1 estimates the hypothetical maximum impact. Relying entirely on indirect effects, Models 2 and 3 represent the minimum impact of PCV. Predictions would be more accurate if they accounted for direct effects among vaccinated VT carriers. This study illustrates the importance of capturing vaccination data on individuals sampled in carriage prevalence surveys designed to estimate IPD burden at population level.

Background The InBios SCoV-2 Detect™ IgG ELISA (InBios) and the in-house KWTRP ELISA (KWTRP) have both been used in the estimation of SARS-CoV-2 seroprevalence in Kenya. Whereas the latter has been validated extensively using local samples, the former has not. Such validation is important for informing the comparability of data across the sites and populations where seroprevalence has been reported. Methods We compared the assays directly using pre-pandemic serum/plasma collected in 2018 from 454 blood donors and 173 malaria cross-sectional survey participants, designated gold standard negatives. As gold standard SARS-CoV-2 positive samples: we assayed serum/plasma from 159 SARS-CoV-2 PCR-positive patients and 166 vaccination-confirmed participants. Results The overall agreement on correctly classified samples was >0.87 for both assays. The overall specificity was 0.89 (95% CI, 0.87–0.91) for InBios and 0.99 (95% CI, 0.97–0.99) for KWTRP among the gold standard negative samples while the overall sensitivity was 0.97 (95% CI, 0.94–0.98) and 0.93 (95% CI, 0.90– 0.95) for InBios and KWTRP ELISAs respectively, among the gold standard positive samples. In all, the positive predictive value for InBios was 0.83 (95% CI, 0.79-0.87) and 0.98 (95% CI, 0.96-0.99) for KWTRP while the negative predictive value was 0.98 (95% CI, 0.97- 0.99) and 0.97 (95% CI, 0.95-0.98) for InBios and KWTRP respectively. Conclusions Overall, both assays showed sufficient sensitivity and specificity to estimate SARS-CoV-2 antibodies in different populations in Kenya.

Although active vaccine safety surveillance (VSS) can complement passive VSS while overcoming the inherent limitations of spontaneous safety monitoring, it remains rare in sub-Saharan Africa. We conducted post-authorization active VSS of COVID-19 vaccines in Kilifi, Kenya using a cohort event monitoring study design. Participants were followed weekly over 13 weeks for adverse events. A subset was followed daily for one week for solicited systemic reactogenicity events (chills, fatigue, fever, headache, joint pain, malaise, muscle aches, nausea). The daily prevalence of reactogenicity events was compared to the 3-day pre-vaccine average using McNemar's test. The association of baseline characteristics with reactogenicity events was assessed using logistic regression. Between 28th September 2022 and 30th June 2023, 2,440 participants were enrolled into the cohort; 1,000 systematically sampled participants were included in the reactogenicity sub-study. Most were aged 17-39 years (1683; 69.0%) and were female (1895; 77.7%); 535 (28.2%) female participants were pregnant. The three most frequently reported reactogenicity events were fatigue (422; 44.1%), headache (370; 38.7%), and malaise (346; 36.2%); the proportion of severe events ranged from 2.3% (22; nausea) to 5.0% (48; malaise). Except for headache, the prevalence of systemic reactogenicity events was significantly higher in the first two days post-vaccination than pre-vaccination (p-values <0.05). The odds of reactogenicity events were higher among non-pregnant women (adjusted odds ratio [aOR] 1.81; 95% CI 1.28-2.55) and pregnant women (aOR 1.69; 1.03-2.78) than among men, and higher among Johnson & Johnson (aOR 2.05; 1.40-3.00) and Moderna (aOR 4.19; 2.34-7.51) vaccine recipients than among Pfizer vaccine recipients. The prevalence of pregnancy complications was 2.6% (95% CI 1.4-3.5%) against a background prevalence of 3-49%. Reactogenicity events following COVID-19 vaccination were generally non-severe and transient. There was no elevated risk of pregnancy-related complications. Addressing operational barriers is essential for enhancing the utility and feasibility of future active VSS.

The Kenya Multi Site Serosurveillance (KEMIS) collaboration set out to implement an integrated, nationally representative, population-based program of serological surveillance for past infection for a number of important infectious diseases in Kenya. The project started in December 2021 and built on a portfolio of SARS-CoV-2 research conducted in 2020 and 2021. In this profile paper, we describe the background of the KEMIS collaboration, its aim and objectives, the Health and Demographic Surveillance System sites that were involved in data collection, and the key activities undertaken. We also explain how we established governance and management of the KEMIS collaboration, and reflect on opportunities, challenges, lessons learned, and future directions.

Background:The InBios SCoV-2 Detect™ IgG ELISA (InBios) and the in-house KWTRP ELISA (KWTRP) have both been used in the estimation of SARS-CoV-2 seroprevalence in Kenya. Whereas the latter has been validated extensively using local samples, the former has not. Such validation is important for informing the comparability of data across the sites and populations where seroprevalence has been reported. Methods:We compared the assays directly using pre-pandemic serum/plasma collected in 2018 from 454 blood donors and 173 malaria cross-sectional survey participants, designated gold standard negatives. As gold standard SARS-CoV-2 positive samples: we assayed serum/plasma from 159 SARS-CoV-2 PCR-positive patients and 166 vaccination-confirmed participants. Results:The overall agreement on correctly classified samples was >0.87 for both assays. The overall specificity was 0.89 (95% CI, 0.87-0.91) for InBios and 0.99 (95% CI, 0.97-0.99) for KWTRP among the gold standard negative samples while the overall sensitivity was 0.97 (95% CI, 0.94-0.98) and 0.93 (95% CI, 0.90- 0.95) for InBios and KWTRP ELISAs respectively, among the gold standard positive samples. In all, the positive predictive value for InBios was 0.83 (95% CI, 0.79-0.87) and 0.98 (95% CI, 0.96-0.99) for KWTRP while the negative predictive value was 0.98 (95% CI, 0.97- 0.99) and 0.97 (95% CI, 0.95-0.98) for InBios and KWTRP respectively. Conclusions:Overall, both assays showed sufficient sensitivity and specificity to estimate SARS-CoV-2 antibodies in different populations in Kenya.

Increased immune evasion by emerging and highly mutated SARS-CoV-2 variants is a key challenge to the control of COVID-19. The majority of these mutations mainly target the spike protein, allowing the new variants to escape the immunity previously raised by vaccination and/or infection by earlier variants of SARS-CoV-2. In this study, we investigated the neutralizing capacity of antibodies against emerging variants of interest circulating between May 2023 and March 2024 using sera from representative samples of the Kenyan population. From our genomics data, we identified the most prevalent Kenyan and global variants and performed pseudoviruses neutralization assays with the most recent SARS-CoV-2 variants. Our data show that antibodies from individuals in the general population in Kenya were less effective against the recent prevalent SARS-CoV-2 omicron variants (i.e. EG.5.1, FY.4, BA.2.86, JN.1, and JN.1.4) compared to the ancestral wildtype strain. Although there was increased neutralization following multiple doses of vaccine, antibodies from >40% of the vaccinated individuals did not neutralize the omicron variants, suggesting that individuals were susceptible to infection by these variants. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Wellcome Trust (grants 226141/Z/22/Z, 226130/Z/22/Z, 227131/Z/23/Z & 227131/B/23/Z 226141/Z/22/Z and 226002/A/22/Z), MRC (MR/W005611/1, MR/Y004205/1), BBSRC (BBS/E/I/COV07001, BBS/E/I/00007031), and Bill and Melinda Gates Foundation (INV-039626). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Kenya Medical Research Institute, Scientific Ethics Review Unit gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Add data produced are available online at https://doi.org/10.7910/DVN/6DSHMB

Background There are only a few long-term PCV impact assessments in sub-Saharan Africa, and these have been confined to settings using a 13-valent PCV. A 10-valent PCV was introduced in Kenya in 2011 with catchup vaccination among children aged <5 years in Kilifi. We evaluated the impact of PCV10 introduction in Kilifi through 2022. Methods Surveillance for IPD among residents of the Kilifi Health and Demographic Surveillance System was conducted at the Kilifi County Referral Hospital. Identification of pneumococcus isolated from blood or cerebrospinal fluid and pneumococcal serotyping were conducted according to WHO recommendations. Age– and serotype-specific incidence rate ratios, adjusted for pre-defined confounders (aIRRs), were used to compare annual IPD incidence in the pre-vaccine period to that in 2017-2019 (late post-vaccine) and 2020-2022 (COVID-19). Findings Compared to the pre-vaccine period, the incidence of vaccine serotype (VT) IPD among children aged <5 years was significantly lower in 2017-2019 (aIRR 0.14; 95%CI 0.04-0.49) and in 2020-2022 (aIRR 0.03; 95%CI 0.00-0.25). It also declined among older children and adults. The incidence of non-VT (NVT) IPD among children aged <15 years was higher during the post-vaccine period. All serotype IPD incidence declined across all age groups. Among individuals with NVT-IPD, serotypes included in new-generation PCVs accounted for about one-third and about one-half of disease among individuals aged <5 years and ≥5 years, respectively. Interpretation Despite potential waning of the effects of catchup vaccination during introduction, reductions in VT-IPD incidence were sustained through 12 years of PCV10 use. All serotype IPD incidence declined across all ages despite serotype replacement among children. New-generation PCVs may enhance IPD control. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Gavi, The Vaccine Alliance. EWK was funded by the Foreign Commonwealth & Development Office and the Bill & Melinda Gates Foundation ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval to conduct the study was granted by Kenya Medical Research Institute Scientific Ethics Review Unit (SSC 1433) and the Oxford Tropical Research Ethics Committee (30-10). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

Increased immune evasion by emerging and highly mutated SARS-CoV-2 variants is a key challenge to the control of COVID-19. The majority of these mutations mainly target the spike protein, allowing the new variants to escape the immunity previously raised by vaccination and/or infection by earlier variants of SARS-CoV-2. In this study, we investigated the neutralizing capacity of antibodies against emerging variants of interest circulating between May 2023 and October 2024 using sera from representative samples of the Kenyan population. From our genomics data, we identified the most prevalent Kenyan and global variants and performed pseudoviruses neutralization assays with the most recent SARS-CoV-2 variants. Our data show that antibodies from individuals in the general population in Kenya were less effective against the recent prevalent SARS-CoV-2 omicron variants (i.e. EG.5.1, FY.4, BA.2.86, JN.1, JN.1.4, and KP.3.1.1) compared to the ancestral wildtype strain. Although there was increased neutralization following multiple doses of vaccine, antibodies from > 40

Background In Kilifi (Kenya), a pneumococcal conjugate vaccine (PCV10) was introduced in 2011 in infants (aged <1 year, 3 + 0 schedule) with a catch-up campaign in children aged 1-4 years. We aimed to measure the effect of PCV10 on population immunity. Methods In this observational study, repeated cross-sectional serosurveys were conducted in independent random samples of 500 children younger than 15 years every 2 years between 2009 and 2017. During these surveys, blood samples were collected by venesection. Concentrations of anti-capsular IgGs against vaccine serotypes (VTs) 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F, and against serotypes 6A and 19A, were assayed by ELISA. We plotted the geometric mean concentrations (GMCs) by birth year to visualise age-specific antibody profiles. In infants, IgG concentrations of 0 center dot 35 pg/mL or higher were considered protective.Findings Of 3673 volunteers approached, 2152 submitted samples for analysis across the five surveys. Vaccine introduction resulted in an increase in the proportion of young children with protective IgG concentrations, compared with before vaccine introduction (from 0-33% of infants with VT-specific levels over the correlate of protection in 2009, to 60-94% of infants in 2011). However, among those vaccinated in infancy, GMCs of all ten VTs had waned rapidly by the age of 1, but rose again later in childhood. GMCs among children aged 10-14 years were consistently high over time (eg, the range of GMCs across survey rounds were between 045 mu g/mL and 100 mu g/mL for VT 23F and between 200 mu g/mL and 311 mu g/mL for VT 19F).Interpretation PCV10 in a 3 + 0 schedule elicited protective IgG levels during infancy, when disease risk is high. The high antibody levels in children aged 10-14 years might indicate continued exposure to vaccine serotypes due to residual carriage or to memory responses to cross-reactive antigens. Despite rapid waning of IgG after vaccination, disease incidence among young children in this setting remains low, suggesting that lower thresholds of antibody, or other markers of immunity (eg, memory B cells), may be needed to assess population protection among children who have aged past infancy.Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Bacteriocins are antimicrobial peptides produced by bacteria to inhibit other bacteria in the surrounding environment. Streptococcus pneumoniae is a leading cause of disease worldwide and colonises the healthy human nasopharynx, where it competes for space and nutrients. Pneumococcal conjugate vaccines have reduced the incidence of disease, but they also restructure the bacterial population, and this restructuring likely alters the nasopharyngeal competition dynamics. Here, the distribution of bacteriocins was examined in over 5000 carriage and disease-causing pneumococci from Iceland and Kenya, recovered before and after the introduction of pneumococcal vaccination. Overall, up to eleven different bacteriocin gene clusters were identified per pneumococcus. Significant differences in the prevalence of bacteriocins were observed before and after vaccine introduction, and among carriage and disease-causing pneumococci, which were largely explained by the bacterial population structure. Genetically similar pneumococci generally harboured the same bacteriocins although sometimes different repertoires of bacteriocins were observed, which suggested that horizontal transfer of bacteriocin clusters had occurred. These findings demonstrated that vaccine-mediated changes in the pneumococcal population altered the prevalence and distribution of bacteriocins. The consequences of this for pneumococcal colonisation and disease remain to be determined.

Pneumococcal conjugate vaccines (PCVs) protect against invasive pneumococcal disease (IPD) among vaccinees. However, at population level, this protection is driven by indirect effects. PCVs prevent nasopharyngeal acquisition of vaccine-serotype (VT) pneumococci, reducing onward transmission. Each disease episode is preceded by infection from a carrier, so vaccine impacts on carriage provide a minimum estimate of disease reduction in settings lacking expensive IPD surveillance. We documented carriage prevalence and vaccine coverage in two settings in Nigeria annually (2016–2020) following PCV10 introduction in 2016. Among 4,684 rural participants, VT carriage prevalence fell from 21 to 12% as childhood (<5 years) vaccine coverage rose from 7 to 84%. Among 2,135 urban participants, VT carriage prevalence fell from 16 to 9% as uptake rose from 15 to 94%. Within these ranges, carriage prevalence declined with uptake. Increasing PCV10 coverage reduced pneumococcal infection at all ages, implying at least a comparable reduction in IPD.