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Plain Language SummaryWhat is the context?The WHO added the pneumococcal conjugate vaccine and the rotavirus vaccine in the recommended vaccination schedule of all countries in 2007 and 2009, respectively.Previous studies estimated the public health benefit of these vaccines by approximating the number of children who received them.What is new?We used an alternative approach to estimate the benefit based on actual number of doses of the vaccines, human rotavirus vaccine (HRV; Rotarix) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix) delivered to each country considered.The study analyzed data from children under 5 years of age in 60 Gavi-supported countries by identifying the number of vaccine doses delivered, estimating the number of children fully covered, applying the country-specific disease epidemiology, estimating the number of severe disease cases and deaths avoided.From 2009 to 2019, approximately 143 million children were vaccinated with HRV avoiding an estimated 18.7 million severe rotavirus disease cases and 153,000 deaths.From 2011 to 2019, about 146 million children were vaccinated with pneumococcal vaccine avoiding an estimated 5.0 million severe pneumococcal disease cases and 587,000 deaths.What is the impact?The benefit of HRV and PHiD-CV in Gavi-supported countries is often estimated based on assumptions of vaccine coverage rates.A modeling approach based on doses delivered by the vaccine manufacturer can provide an additional view on the potential vaccine benefits and improve planning, contribution, and sustainability of the immunization programs at a country level.In 2019, HRV and PHiD-CV together averted nine cases of severe disease each minute and one child death every 4 minutes. Vaccine impact models against rotavirus disease (RD) and pneumococcal disease (PD) in low- and middle-income countries assume vaccine coverage based on other vaccines. We propose to assess the impact on severe disease cases and deaths avoided based on vaccine doses delivered by one manufacturer to Gavi-supported countries. From the number of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) doses delivered, we estimated the averted burden of disease 1) in a specific year and 2) for all children vaccinated during the study period followed-up until 5 years (y) of age. Uncertainty of the estimated impact was assessed in a probabilistic sensitivity analysis using Monte-Carlo simulations to provide 95% confidence intervals. From 2009 to 2019, approximately 143 million children received HRV in 57 Gavi-supported countries, avoiding an estimated 18.7 million severe RD cases and 153,000, deaths. From 2011 to 2019, approximately 146 million children received PHiD-CV in 36 countries, avoiding an estimated 5.0 million severe PD cases and 587,000 deaths. The number of severe cases and deaths averted for all children vaccinated during the study period until 5 years of age were about 23.2 million and 190,000, respectively, for HRV, and 6.6 million and 749,000, respectively, for PHiD-CV. Models based on doses delivered help to assess the impact of vaccination, plan vaccination programs and understand public health benefits. In 2019, HRV and PHiD-CV doses delivered over a 5-y period may have, on average, averted nine severe disease cases every minute and one child death every 4 min. GlaxoSmithKline Biologicals SA funded this study and was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also paid all costs associated with the development and publication of this manuscript. The authors would like to thank Tathyana Giannotti Cousseau for her input regarding the initiation, collection of the actual sales volume per year and assessment of various methodologies adopted by Supranational agencies like Gavi and John Hopkins for “Lives Saved” model. The authors would also like to thank Business & Decision Life Sciences platform for editorial assistance and manuscript coordination, on behalf of GSK, and TVF communications platform for the design support for the digital illustration, on behalf of GSK. Mary Greenacre (An Sgriobhadair Ltd) provided writing support for this literature review.

ImportancePrevious studies have analyzed effectiveness of booster mRNA Covid-19 vaccination and compared it with 2-dose primary series for both Delta and Omicron variants. Observational studies that estimate effectiveness by comparing outcomes among vaccinated and unvaccinated individuals may suffer from residual confounding and exposure misclassification.ObjectiveTo estimate relative effectiveness of booster vaccination versus the 2-dose primary series with self-controlled study designDesign, Setting and ParticipantsWe used the Veterans Health Administration (VHA) Corporate Data Warehouse to identify U.S. Veterans enrolled in care ≥2 years who received the 2-dose primary mRNA Covid-19 vaccine series and a mRNA Covid-19 booster following expanded recommendation for booster vaccination, and who had a positive SARS-CoV-2 test during the Delta (9/23/2021-11/30/2021) or Omicron (1/1/22-3/1/22) predominant period. Among them, we conducted a self-controlled risk interval (SCRI) analysis to compare odds of SARS-CoV-2 infection during a booster exposure interval versus a control interval.Exposurescontrol interval (days 4-6 post-booster vaccination, presumably prior to gain of booster immunity), and booster exposure interval (days 14-16 post-booster vaccination, presumably following gain of booster immunity)Outcomes and MeasuresPositive PCR or antigen SARS-CoV-2 test. Separately for Delta and Omicron periods, we used conditional logistic regression to calculate odds ratios (OR) of a positive test for the booster versus control interval and calculated relative effectiveness of booster versus 2-dose primary series as (1-OR)*100. The SCRI approach implicitly controlled for time-fixed confounders.ResultsWe found 42 individuals with a positive SARS-CoV-2 test in the control interval and 14 in the booster exposure interval during Delta period, and 137 and 66, respectively, in Omicron period. For the booster versus 2-dose primary series, the odds of infection were 70% (95%CI: 42%, 84%) lower during the Delta period and 56% (95%CI: 38%, 67%) lower during Omicron. Results were similar for ages ConclusionsBooster vaccination was more effective relative to a 2-dose primary series, the relative effectiveness was consistent across age groups and was higher during the Delta predominant period than during the Omicron period.

Background Approximately 50 000 influenza-associated deaths occur annually in the United States, overwhelmingly among individuals aged ≥65 years. Although vaccination is the primary prevention tool, investigations have shown low vaccine effectiveness (VE) in recent years, particularly among the elderly. We analyzed the relative VE (RVE) of all influenza vaccines among Medicare beneficiaries aged ≥65 years to prevent influenza hospital encounters during the 2019–2020 season. Methods Retrospective cohort study using Poisson regression and inverse probability of treatment weighting (IPTW). Exposures included egg-based high-dose trivalent (HD-IIV3), egg-based adjuvanted trivalent (aIIV3), egg-based standard dose (SD) quadrivalent (IIV4), cell-based SD quadrivalent (cIIV4), and recombinant quadrivalent (RIV4) influenza vaccines. Results We studied 12.7 million vaccinated beneficiaries. Following IPTW, cohorts were well balanced for all covariates and health-seeking behavior indicators. In the adjusted analysis, RIV4 (RVE, 13.3%; 95% CI, 7.4–18.9%), aIIV3 (RVE, 8.2%; 95% CI, 4.2–12.0%), and HD-IIV3 (RVE, 6.8%; 95% CI, 3.3–10.1%) were significantly more effective in preventing hospital encounters than the reference egg-based SD IIV4, while cIIV4 was not significantly more effective than IIV4 (RVE, 2.8%; 95% CI, −2.8%, 8.2%). Our results were consistent across all analyses. Conclusions In this influenza B-Victoria and A(H1N1)–dominated season, RIV4 was moderately more effective than other vaccines, while HD-IIV3 and aIIV3 were more effective than the IIV4 vaccines, highlighting the contributions of antigen amount and adjuvant use to VE. Egg adaptation likely did not substantially affect our RVE evaluation. Our findings, specific to the 2019–2020 season, should be evaluated in other studies using virological case confirmation.

Community-acquired pneumonia (CAP) is a common infection with significant morbidity and mortality. In January 2017, Poland introduced pneumococcal conjugate vaccine (PCV) into their national immunisation programme to protect children against invasive pneumococcal disease. This study was designed to investigate pneumonia-related hospitalisation rates and trends from 2009 to 2016 prior to the introduction of nationally funded PCV vaccination.Using national public statistic data available from the National Institute of Public Health - National Institute of Hygiene, annual hospitalisation rates for pneumonia were analysed, categorised by aetiology and age (2, 2-3, 4-5, 6-19, 20-59, 60+ years). Trends over time were assessed, as well as in-hospital mortality.The overall hospitalisation rate due to pneumonia varied between 325.9 and 372.2/100,000 population. Higher rates of hospitalisation were seen in older adults and children ≤5 years. Trends were observed when analysing hospitalisations by pneumonia aetiology within age groups: between 2009 and 2016, Streptococcus pneumoniae hospitalisations significantly increased for children aged2, 2-3, and 4-5 years, from 5.3 to 12.4, 5.2 to 8.2, and 1.9 to 4.6/100,000 population respectively. Whereas hospitalisations due to Haemophilus influenzae pneumonia decreased significantly from 7.8 to 1.8 and 4.8 to 1.9/100,000 children aged2 and 2-3 years respectively. The numbers of in-hospital deaths increased from 5578 in 2009 to 8149 in 2016, with85% of deaths in the 60+ age group.This is the first national study of pneumonia hospitalisations in Poland, providing the baseline data from which to investigate the impact of the change in vaccination policy on pneumonia hospitalisations in Poland.

Otitis media (OM) is a common disease of childhood and available pneumococcal conjugate vaccines (PCVs), with different compositions, could have different impact on OM reduction. This systematic literature review evaluated available data describing the efficacy, effectiveness, and impact of 10-valent pneumococcalPlain Language Summary

Key Points Question What was the COVID-19 vaccination coverage and estimated mRNA COVID-19 vaccine effectiveness (VE) among US veterans in the first 3 months following vaccine rollout? Findings In this case-control study including 6 647 733 veterans, 23% of veterans received at least 1 COVID-19 vaccination during the first 3 months of vaccine rollout. VE against infection was estimated to be 95% for full vaccination; estimated VE against COVID-19-related hospitalization was 91%, and there were no COVID-19–related deaths among fully vaccinated veterans. Meaning These findings suggest that early vaccination rollout for veterans was efficient, and estimated VE was high for this diverse US population., This case-control study describes the scope of the mRNA COVID-19 vaccination rollout and estimates the association between vaccination and reductions in SARS-CoV-2 infections among veterans during the first 3 months of vaccine rollout., Importance Effectiveness of mRNA vaccinations in a diverse older population with high comorbidity is unknown. Objectives To describe the scope of the COVID-19 vaccination rollout among US veterans, and to estimate mRNA COVID-19 vaccine effectiveness (VE) as measured by rates of SARS-CoV-2 infection. Design, Setting, and Participants This matched test–negative case-control study was conducted using SARS-CoV-2 test results at Veterans Health Administration sites from December 14, 2020, to March 14, 2021. Vaccine coverage was estimated for all veterans. VE against SARS-CoV-2 infection and COVID-19–related hospitalization and death were estimated using electronic health records from veterans who routinely sought care at a VHA facility and had a test result positive for SARS-CoV-2 (cases) or negative for SARS-CoV-2 (controls). Cases and controls were matched on time of test and geographic region. Data were analyzed from May to July 2021. Exposures Vaccination status, defined as unvaccinated, partially vaccinated (≥14 days after first dose until second dose), or fully vaccinated (≥14 days after second dose), at time of test. Main Outcomes and Measures The main outcome of interest was a positive result for SARS-CoV-2 on a polymerase chain reaction or antigen test. Secondary outcomes included COVID-19–related hospitalization and death, defined by discharge data and proximity of event to positive test result. VE was estimated from odds ratios for SARS-CoV-2 infection with 95% CIs. Results Among 6 647 733 veterans included (3 350 373 veterans [50%] aged ≥65 years; 6 014 798 [90%] men and 632 935 [10%] women; 461 645 Hispanic veterans of any race [7%], 1 102 471 non-Hispanic Black veterans [17%], and 4 361 621 non-Hispanic White veterans [66%]), 1 363 180 (21%) received at least 1 COVID-19 vaccination by March 7, 2021. In this period, during which the share of SARS-CoV-2 variants Alpha, Epsilon, and Iota had started to increase in the US, estimates of COVID-19 VE against infection, regardless of symptoms, was 95% (95% CI, 93%-96%) for full vaccination and 64% (95% CI, 59%-68%) for partial vaccination. Estimated VE against COVID-19–related hospitalization for full vaccination was 91% (95% CI 83%-95%); there were no deaths among veterans who were fully vaccinated. VE against infection was similar across subpopulations (non-Hispanic Black, 94% [95% CI, 88%-97%]; Hispanic [any race], 83% [95% CI, 45%-95%]; non-Hispanic White, 92% [95% CI 88%-94%]; rural, 94% [95% CI, 89%-96%]; urban, 93% 95% CI, 89%-95%]). Conclusions and Relevance For veterans of all racial and ethnic subgroups living in urban or rural areas, mRNA vaccination was associated with substantially decreased risk of COVID-19 infection and hospitalization, with no deaths among fully vaccinated veterans.

Importance The scope of vaccination rollout and effectiveness of mRNA SARS-CoV-2 vaccines in the United States (US), and US Veterans specifically, has not been fully assessed. Objective To estimate receipt of SARS-CoV-2 vaccines, and vaccine effectiveness (VE) against SARS-CoV-2 infection, subsequent disease-related severity and mortality. Design, Setting, and Participants First, receipt of any SARS-CoV-2 vaccine by March 7, 2021 was described for all enrolled and alive Veterans within the Veterans Health Administration (VHA). Second, to evaluate mRNA SARS-CoV-2 VE, a matched test negative case-control evaluation was conducted across all VHA facilities utilizing SARS-CoV-2 positive (cases [n=16,690]) and negative (controls [n=61,610]) tests from Veterans aged ≥18 years old who routinely sought care at a VHA facility and were tested for SARS-CoV-2 from December 14, 2020, through March 14, 2021. Exposures Vaccination histories were obtained from pharmacy and medical records to determine if patients were unvaccinated, partially vaccinated (from 7 days after first dose until day of second dose of mRNA SARS-CoV-2 vaccine), or fully vaccinated (from 7 days after second dose of mRNA SARS-CoV-2 vaccine) at time of SARS-CoV-2 test. Main Outcome Measures Primary outcomes were (1) vaccine receipt among Veterans and specific subpopulations, (2) VE calculated from odds ratios (ORs) with 95% confidence intervals (95% CI) for the association between SARS-CoV-2 infection and full vs. no vaccination, and (3) VE against infection for partial vs. no vaccination. VE against COVID-19-related hospitalization and death were also estimated. Results By March 7, 2020, among 6,170,750 Veterans, 1,547,045 (23.1%) received at least one SARS-CoV-2 vaccine. Based on the analysis of mRNA SARS-CoV-2 vaccines, VE against infection was 93.7% (95% CI 92.0-95.0) and 57.7% (95% CI 53.5-61.5) for full and partial vaccination (vs. no vaccination), respectively. VE was similar for subpopulations. VE against COVID-19-related hospitalization and death for full vs. no vaccination was 90.7% (95% CI 90.0-91.3) and 94.7% (95% CI 91.3-98.1), respectively. Conclusion and Relevance Vaccines are effective in reducing SARS-CoV-2 infections and disease-related severity and mortality in the Veteran population. Effective vaccine, as well as their efficient and equitable distribution, are important for reducing COVID-19 disease burden among Veterans. Key Points Question What is the scope of VHA vaccination rollout and the impact of mRNA SARS-CoV-2 vaccination among Veterans? Findings Vaccination rollout reached all Veteran subpopulations in the first three months. Effectiveness of full vaccination with mRNA SARS-CoV-2 vaccines was 93.7% for preventing infection, comparable to that demonstrated in clinical trials. Effectiveness was similarly high for the elderly, ethnic and racial minorities, individuals with low income, homeless persons, and immunocompromised Veterans. Meaning Effective vaccines and their efficient and equitable distribution helped the VHA to reduce COVID-19 disease burden and disparities among Veterans within the first three months of vaccine distribution.

Background Guillain-Barre syndrome (GBS) is a serious acute demyelinating disease, an increased risk of which was found after the 1976 swine flu vaccinations. The U.S. Food and Drug Administration, in collaboration with the Centers for Medicare & Medicaid Services, has been conducting active surveillance for GBS after influenza vaccinations of Medicare Fee-For-Service beneficiaries since 2009. Methods We conducted active surveillance for GBS claims in the 2015–2016 and 2016–2017 influenza seasons using the Updating Sequential Probability Ratio Test (USPRT) to monitor for signals of GBS risk. We performed self-controlled risk interval (SCRI) analyses at the end of both seasons, including chart confirmation in the 2015–2016 season, to estimate the odds ratio of GBS risk. We used 1–42 and 8–21 days post-vaccination as primary and secondary risk windows, respectively, and 43–84 days post-vaccination as the control window. Results Over 13 million beneficiaries were vaccinated in each season. USPRT found a low magnitude signal for GBS in both seasons. SCRI analyses did not find excess GBS risk following any influenza vaccine for days 1–42 post-vaccination in either season. In the 2015–2016 season, for the 8–21 day window, our chart-confirmation showed an attributable GBS risk of 0.87 (95% CI: 0.16, 1.49) and 1.68 (95% CI: 0.69, 2.41) cases per million vaccinees after all seasonal and high dose (HD) vaccines, respectively, an elevated GBS risk for beneficiaries aged ≥75 years following all seasonal vaccines (OR: 2.25; 95% CI: 1.15, 4.39) and HD vaccine (OR: 3.67, 95% CI: 1.52, 8.85), and an elevated GBS risk for males who received seasonal vaccines (OR: 2.18; 95% CI: 1.15, 4.15) and HD vaccine (OR: 3.33; 95% CI: 1.35, 8.20). The finding of elevated GBS risk with advancing age and in males is consistent with literature; however, a distinction between HD and SD was a new finding. In the 2016–17 season, for the 8–21 day window, attributed cases showed an attributable GBS risk of 0.87 (95% CI: 0.03, 1.61) and 1.11 (95% CI: 0.00, 2.01) cases per million vaccinees after all seasonal and HD vaccines, respectively. We found no excess GBS risk for standard dose vaccines in the 8–21 day window in either season. Conclusions Our primary analysis finding of no excess GBS risk during both seasons was reassuring. The slightly elevated GBS risk, although in the expected range, in the 8–21 day window after all seasonal and high dose vaccines, but not after standard dose vaccines is hypothesis-generating because the difference may be due to vaccine factors such as antigen amount or strains in various seasons or due to host factors.

Background The low influenza vaccine effectiveness (VE) observed during the A(H3N2)-dominated 2017–2018 season may be due to vaccine virus adaptation to growth in eggs. We compared the effectiveness of cell-cultured and egg-based vaccines among Medicare beneficiaries. Methods Retrospective cohort study on Medicare beneficiaries aged ≥65 years who received an influenza vaccine (cell-cultured, egg-based quadrivalent; egg-based high-dose, adjuvanted, or standard-dose trivalent) during the 2017–2018 season. We used Poisson regression to evaluate relative VE (RVE) in preventing influenza-related hospital encounters. Results Of >13 million beneficiaries, RVE for cell-cultured vaccines relative to egg-based quadrivalent vaccines was 10% (95% confidence interval [CI], 7%–13%). In a midseason interim analysis, this estimate was 16.5% (95% CI, 10.3%–22.2%). In a 5-way comparison, cell-cultured (RVE, 11%; 95% CI, 8%–14%) and egg-based high-dose (RVE, 9%; 95% CI, 7%–11%) vaccines were more effective than egg-based quadrivalent vaccines. Conclusions The modest VE difference between cell-cultured and egg-based vaccines only partially explains the low overall VE reported by the Centers for Disease Control and Prevention, suggesting that egg adaptation was not the main contributor to the low VE found among individuals aged ≥65 years. The midseason interim analysis we performed demonstrates that our methods can be used to evaluate VE actively during the influenza season.

Streptococcus pneumoniae is a major cause of morbidity and mortality, especially amongst young children and the elderly. Childhood implementation of pneumococcal conjugate vaccines (PCVs) significantly reduced the incidence of invasive pneumococcal disease (IPD), while several nonvaccine serotypes remained substantial. Although there is evidence of the impact of higher-valent PCVs on serotype 19A, 19A IPD burden and antibiotic resistance remain a major concern post-vaccination. We performed a systematic literature review to analyze the frequency and clonal distribution of serotype 19A isolates in the pre– and post-PCV era worldwide providing a scientific background on the factors that influence multidrug resistance in pneumococcal isolates. Serotype 19A IPD incidence increased in all regions following the introduction of the 7-valent PCV. The higher-valent PCVs have reduced the rates of 19A IPD isolates, but several circulating strains with diverse antibiotic resistance prevailed. Heterogeneous clonal distribution in serotype 19A was observed within countries and regions, irrespective of higher-valent PCV used. An increase of 19A isolates from pre- to post-vaccination periods were associated with frequently occurring serotype switching events and with the prevalence of multidrug resistant strains. Rational antibiotic policies must be implemented to control the emergence of resistance. Plain Language Summary What is the context? Streptococcus pneumoniae is a major cause of pneumococcal diseases especially amongst young children and the elderly. Vaccination with pneumococcal conjugate vaccines has significantly reduced the incidence of invasive pneumococcal disease worldwide. However, the invasive pneumococcal disease remains an important health problem due to the increase of nonvaccine serotypes. Serotype 19A is predominant in many countries worldwide. Factors contributing to its prevalence include serotype replacement, the emergence of clones with multidrug resistance due to antibiotic overuse, and potential bacteria adaptation in response to the vaccine. What is new? We performed a systematic literature review to 1) analyze the incidence and clonal distribution of serotype 19A isolates pre- and post-vaccination worldwide, and to collect data evaluating antimicrobial resistance patterns displayed by the clones of serotype 19A. We found that 1) clonal distribution in serotype 19A was heterogeneous within countries and regions, irrespective of the vaccine used; 2) the diversity of 19A isolates increased after vaccination. It was associated with frequent serotype switching events and with the prevalence of multidrug resistant strains. What is the impact? Implementation of policies to educate on sustainable antibiotic use and infectious prevention measures may help control the emergence of antibiotic resistance. High-quality active surveillance and future molecular epidemiology studies are needed to understand rapid genetic changes.

Background Tens of millions of seniors are at risk of herpes zoster (HZ) and its complications. Live attenuated herpes zoster vaccine (HZV) reduces that risk, although questions regarding effectiveness and durability of protection in routine clinical practice remain. We used Medicare data to investigate HZV effectiveness (VE) and its durability. Methods This retrospective cohort study included beneficiaries ages ≥65 years during January 2007 through July 2014. Multiple adjustments to account for potential bias were made. HZV-vaccinated beneficiaries were matched to unvaccinated beneficiaries (primary analysis) and to HZV-unvaccinated beneficiaries who had received pneumococcal vaccination (secondary analysis). HZ outcomes in community and hospital settings were analyzed, including ophthalmic zoster (OZ) and postherpetic neuralgia (PHN). Results Among eligible beneficiaries (average age 77 years), the primary analysis found VE for community HZ of 33% (95% CI: 32%-35%) and 19% (95% CI: 17%-22%), for the first 3, and subsequent 4+ years postvaccination, respectively. In the secondary analysis, VE was, respectively, 37% (95% CI: 36%-39%) and 22% (95% CI: 20%-25%). In the primary analysis, VE for PHN was 57% (95% CI: 52%-61%) and 45% (95% CI: 36%-53%) in the first 3 and subsequent 4+ years, respectively; VE for hospitalized HZ was, respectively, 74% (95% CI: 67%-79%) and 55% (95% CI: 39%-67%). Differences in VE by age group were not significant. Conclusions In both the primary and secondary analyses, HZV provided protection against HZ across all ages, but effectiveness declined over time. VE was higher and better preserved over time for PHN and HZ-associated hospitalizations than for community HZ.

Background Stockpiling vaccine for deployment in the event of an influenza pandemic is an important mitigation strategy. A necessary aspect of stockpiling is to determine the shelf-life of the stored vaccine. Methods In this Phase II, open-label study we assessed the immunogenicity and safety of H5N1 A/Indonesia/5/2005 vaccine adjuvanted with AS03A. The AS03A-H5N1 vaccine was prepared from bulk antigen that had been stored for 4 years, and adjuvant that had been stored for 2.5 years. Both the antigen and adjuvant were filled in separate multi-dose vials within 4 months of use, and on the day of vaccination, the contents of antigen and adjuvant vials were mixed. Seventy-eight adults aged 18–64 years were scheduled to receive two doses of hemagglutinin-antigen (3.75 μg) given 21 days apart. Antibody responses were assessed by hemagglutination-inhibition (HI) assay according to age (18–30 years, 31–40 years, 41–50 years, and 51–64 years). Reactogenicity was assessed for 7 days after each vaccination, and safety was assessed for 385 days post-vaccination ( NCT01416571 ). Results The vaccine was immunogenic. Twenty-one days after the second dose of vaccine in the overall population, the HI seroconversion rate and seroprotection rate (SPR; titer ≥1:40) was 96.0% and 98.7%, respectively. At Day 182 after vaccination, the SPR was 76.7% in the overall population. Injection site pain was the most frequent solicited adverse event (91.0%), and no safety concerns were raised. Conclusion The immunogenicity and safety observed with AS03A-H5N1 vaccine formulated with bulk antigen which had been stockpiled before vialing and administration was consistent with that previously observed with newly manufactured AS03A-H5N1 vaccine. This suggests that stockpiling bulk antigen for 4 years does not compromise the immunogenicity or reactogenicity of the vaccine.

Background Statins are used to reduce cardiovascular disease risk. Recent studies suggest that statin use may be associated with an increased influenza risk among influenza vaccinees. We used Medicare data to evaluate associations between statins and risks of influenza-related encounters among vaccinees. Methods In this retrospective cohort study, we identified Medicare beneficiaries aged > 65 years who received high-dose (HD) or standard-dose (SD) influenza vaccines at pharmacies from 2010-2011 through 2014-2015. Statin users were matched to nonusers by vaccine type, demographics, prior medical encounters, and comorbidities. We used multivariable Poisson models to estimate associations between statin use around the time of vaccination and risk of influenza-related encounters. Study outcomes included influenza-related office visits with a rapid test followed by dispensing of oseltamivir and influenza-related hospitalizations (including emergency room visits) during high influenza circulation periods. Results The study included 1403651 statin users matched to nonusers. Cohorts were well balanced, with standardized mean differences ≤0.03 for all measured covariates. For statin users compared to nonusers, the adjusted relative risk was 1.086 (95% confidence interval [CI], 1.025-1.150) for influenza-related visits and 1.096 (95% CI, 1.013-1.185) for influenza-related hospitalizations. The risk difference ranged from ‒0.02 to 0.23 for influenza-related visits and from ‒0.04 to 0.13 for hospitalizations, depending on season severity. Results were similar for HD and SD vaccinees and for nonsynthetic and synthetic statin users. Conclusions Among 2.8 million Medicare beneficiaries, these results suggest that statin use around the time of vaccination does not substantially affect the risk of influenza-related medical encounters among older adults.

Background. This phase 2/3, randomized, placebo-controlled, observer-blinded study assessed the immunogenicity, reactogenicity, and safety of an inactivated, split-virion H5N1 influenza vaccine (A/Indonesia/5/2005) in children aged 6 months through 17 years. Methods. Children received 2 influenza vaccine doses 21 days apart, each containing 1.9 µg of hemagglutinin and AS03B adjuvant (5.93 mg of α-tocopherol). The randomization ratio was 8:3 for vaccine to placebo, with equal allocation between 3 age strata (6–35 months, 3–8 years, and 9–17 years). Immunogenicity against the vaccine strain was assessed 21 days after the first and second vaccine doses for all vaccinees, at day 182 for half, and at day 385 for the remaining half. Reactogenicity after each dose and safety up to 1 year after vaccination were evaluated. Results. Within each age stratum, the lower limit of the 98.3% confidence interval for the day 42 seroprotection rate was ≥70%, thus fulfilling the US and European licensure criteria. The immune responses elicited by vaccine persisted well above baseline levels for 1 year. The vaccine was more reactogenic than placebo, but no major safety concerns were identified. Conclusions. AS03B-adjuvanted H5N1 influenza vaccine was immunogenic and showed an acceptable safety profile in all age groups studied. Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT01310413","term_id":"NCT01310413"}}NCT01310413.

Avian influenza A(H5N1) was identified as a cause of death in poultry in 1996, with the first human cases of infection recorded in 1997 [1]. From 2003 until January 2014, influenza A(H5N1) has caused 650 cases of influenza in humans [2]. Around 90% of cases have occurred in individuals

With the advent of new vaccines targeted to highly endemic diseases in low- and middle-income countries (LMIC) and with the expansion of vaccine manufacturing globally, there is an urgent need to establish an infrastructure to evaluate the benefit-risk profiles of vaccines in LMIC. Fortunately the usual decade(s)-long time gap between introduction of new vaccines in high and low income countries is being significantly reduced or eliminated due to initiatives such as the Global Alliance for Vaccines and Immunizations (GAVI) and the Decade of Vaccines for the implementation of the Global Vaccine Action Plan. While hoping for more rapid disease control, this time shift may potentially add risk, unless appropriate capacity for reliable and timely evaluation of vaccine benefit-risk profiles in some LMIC's are developed with external assistance from regional or global level. An ideal vaccine safety and effectiveness monitoring system should be flexible and sustainable, able to quickly detect possible vaccine-associated events, distinguish them from programmatic errors, reliably and quickly evaluate the suspected event and its association with vaccination and, if associated, determine the benefit-risk of vaccines to inform appropriate action. Based upon the demonstrated feasibility of active surveillance in LMIC as shown by the Burkina Faso assessment of meningococcal A conjugate vaccine or that of rotavirus vaccine in Mexico and Brazil, and upon the proof of concept international GBS study, we suggest a sustainable, flexible, affordable and timely international collaborative vaccine safety monitoring approach for vaccines being newly introduced. While this paper discusses only the vaccine component, the same system could also be eventually used for monitoring drug effectiveness (including the use of substandard drugs) and drug safety. Published by Elsevier Ltd.

Estimating risks associated with the use of childhood vaccines is challenging. The authors propose a new approach for studying short-term vaccine-related risks. The method uses a cubic smoothing spline to flexibly estimate the daily risk of an event after vaccination. The predicted incidence rates from the spline regression are then compared with the expected rates under a log-linear trend that excludes the days surrounding vaccination. The 2 models are then used to estimate the excess cumulative incidence attributable to the vaccination during the 42-day period after vaccination. Confidence intervals are obtained using a model-based bootstrap procedure. The method is applied to a study of known effects (positive controls) and expected noneffects (negative controls) of the measles, mumps, and rubella and measles, mumps, rubella, and varicella vaccines among children who are 1 year of age. The splines revealed well-resolved spikes in fever, rash, and adenopathy diagnoses, with the maximum incidence occurring between 9 and 11 days after vaccination. For the negative control outcomes, the spline model yielded a predicted incidence more consistent with the modeled day-specific risks, although there was evidence of increased risk of diagnoses of congenital malformations after vaccination, possibly because of a "provider visit effect." The proposed approach may be useful for vaccine safety surveillance.

BACKGROUND: The risk of immune thrombocytopenic purpura (ITP) after childhood vaccines other than measles-mumps-rubella vaccine (MMR) is unknown. METHODS: Using data from 5 managed care organizations for 2000 to 2009, we identified a cohort of 1.8 million children ages 6 weeks to 17 years. Potential ITP cases were identified by using diagnostic codes and platelet counts. All cases were verified by chart review. Incidence rate ratios were calculated comparing the risk of ITP in risk (1 to 42 days after vaccination) and control periods. RESULTS: There were 197 chart-confirmed ITP cases out of 1.8 million children in the cohort. There was no elevated risk of ITP after any vaccine in early childhood other than MMR in the 12- to 19-month age group. There was a significantly elevated risk of ITP after hepatitis A vaccine at 7 to 17 years of age, and for varicella vaccine and tetanus-diphtheria-acellular pertussis vaccine at 11 to 17 years of age. For hepatitis A, varicella, and tetanus-diphtheria-acellular pertussis vaccines, elevated risks were based on one to two vaccine-exposed cases. Most cases were acute and mild with no long-term sequelae. CONCLUSIONS: ITP is unlikely after early childhood vaccines other than MMR. Because of the small number of exposed cases and potential confounding, the possible association of ITP with hepatitis A, varicella, and tetanus-diphtheria-acellular pertussis vaccines in older children requires further investigation.

The public health community faces increasing demands for improving vaccine safety while simultaneously increasing the number of vaccines available to prevent infectious diseases. The passage of the US Food and Drug Administration (FDA) Amendment Act of 2007 formalized the concept of life-cycle management of the risks and benefits of vaccines, from early clinical development through many years of use in large numbers of people. Harnessing scientific and technologic advances is necessary to improve vaccine-safety evaluation. The Office of Biostatistics and Epidemiology in the Center for Biologics Evaluation and Research is working to improve the FDA's ability to monitor vaccine safety by improving statistical, epidemiologic, and risk-assessment methods, gaining access to new sources of data, and exploring the use of genomics data. In this article we describe the current approaches, new resources, and future directions that the FDA is taking to improve the evaluation of vaccine safety.

Background The 1976–1977 swine influenza vaccine was associated with an elevated risk of Guillain-Barre Syndrome (GBS), especially within 6 weeks after vaccination. A 2004 IOM report concluded that evidence was inadequate to accept or reject a causal relationship between subsequent influenza vaccine formulations and GBS. Studies published after the IOM report have been limited by passively reported data or lack of validation of coded diagnoses. Purpose To evaluate whether influenza vaccine is associated with GBS. Methods Controlled observational study using national data from the Medicare program, which ensures a predominantly elderly population. People included had a Medicare claim for influenza vaccination during September–December in 2000 or 2001. Medical records were reviewed to classify definite, probable, or possible GBS (or not a case) using a standardized case definition. In a risk interval design, the incidence rate of GBS during Weeks 0–6 after vaccination (exposed period) was compared to Weeks 9–14 after vaccination (comparison period). Data collection occurred during 2003–2007, and analysis was conducted during 2007–2009. Results Primary analysis included 22.2 million vaccinees, among whom 164 definite or probable GBS cases with onset during Weeks 0–6 or 9–14 were identified. The incidence rate ratio (IRR [95% CIs]) based on the GBS rate in the vaccine-exposed versus comparison periods, was 1.04 (0.76, 1.43) for combined years; 0.86 (0.52, 1.41) among people vaccinated in 2000; and 1.21 (0.79, 1.86) among people vaccinated in 2001. Secondary analysis additionally included 74 possible GBS cases; results were similar. Conclusions Overall, the results do not support an association between influenza vaccine receipt and GBS among the elderly for the years studied (2000–2001 and 2001–2002 formulations).

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barré syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.

Kawasaki disease (KD) is a multisystemic vasculitis primarily affecting children5 years. A review of RotaTeq (rotavirus vaccine live) clinical trial data revealed higher, though not statistically significantly, KD rates among RotaTeq vaccines than placebo recipients. In June 2007, the RotaTeq label was revised accordingly.To describe and assess KD reported to Vaccine Adverse Event Reporting System (VAERS) for all US licensed vaccines.We reviewed all KD reports received by VAERS from 1990 through mid-October 2007. Cases were characterized by age, gender, onset interval, and vaccine type. Proportional reporting ratio (PRR) was used to evaluate KD reporting for each vaccine compared with all others. Reporting rates were calculated using number of doses distributed as denominator.Through October 14, 2007, 107 KD reports were received by VAERS: 26 were categorized as classic cases, 19 atypical, 52 possible, and 10 were noncases. Of the 97 cases, 91% were children5 years. There was no clustering of onset intervals after day 1 postvaccination. Before the RotaTeq label revision, the KD PRR was elevated only for Pediarix (DTaP, hepB, and IPV combined) but the KD reporting rate for Pediarix (0.59/100,000 person-years) was much lower than the background incidence rate (9-19/100,000 person-years) for children5 years in the United States. After the revision, reporting of KD for RotaTeq was stimulated but the reporting rate for RotaTeq (1.47/100,000 person-years) was still much lower than the background rate.Our review does not suggest an elevated KD risk for RotaTeq or other vaccines. Continued postmarketing monitoring for KD is ongoing.

BACKGROUND. In 1999, a previous rotavirus vaccine (RotaShield; Wyeth Laboratories, Marietta, PA) was withdrawn from the US market after postlicensure monitoring identified an association with intussusception. Although the new rotavirus vaccine (RotaTeq; Merck, West Point, PA) introduced in 2006 was not associated with intussusception in prelicensure trials, additional monitoring is important to ensure a complete safety profile. METHODS. We assessed intussusception reports after RotaTeq vaccination by using data from the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink, a cohort of children enrolled in managed care. Observed versus expected rate ratios were determined by using vaccine dose distribution data and Vaccine Safety Datalink background intussusception rates. RESULTS. Between February 1, 2006, and September 25, 2007, the Vaccine Adverse Event Reporting System received 160 intussusception reports after RotaTeq vaccination. With the assumptions that reporting completeness was 75% and that 75% of the distributed doses of RotaTeq were administered, the observed versus expected rate ratios were 0.53 and 0.91 for the 1–21 and 1–7 day interval after vaccination, respectively. In the Vaccine Safety Datalink, 3 intussusception cases occurred within 30 days after 111521 RotaTeq vaccinations, compared with 6 cases after 186722 non–RotaTeq vaccinations during the same period. If, like RotaShield, RotaTeq had a 37-fold increased risk of intussusception within 3 to 7 days after vaccination, then 8 intussusception cases would be expected within 3 to 7 days among the ∼84000 infants vaccinated with the first dose of RotaTeq in the Vaccine Safety Datalink (N = 49902) and the prelicensure trial (N = 34035) combined, whereas no cases have been observed. CONCLUSIONS. Available data do not indicate that RotaTeq is associated with intussusception. Although an intussusception risk similar in magnitude to that of RotaShield can be excluded, continued monitoring is necessary for complete assessment of the safety profile of RotaTeq.

On October 20, 1997, the U.S. Food and Drug Administration (FDA) licensed Purified Chick Embryo Cell (PCEC, RabAvert®) vaccine against rabies in humans following clinical trials demonstrating safety and efficacy. From October 1997 through December 2005, the Vaccine Adverse Event Reporting System (VAERS) received 336 reports of adverse events (AEs) following vaccination with PCEC vaccine in the U.S.; there were no death reports. Serious events, including 20 hospitalizations and 13 neurological events, were described in 24 (7%) reports. There was no pattern among the 13 neurological AEs suggesting a plausible relationship to vaccination. A total of 20 AEs, 3 serious, were classified as possible anaphylaxis. There were 312 non-serious AEs (93%). Nineteen reports (6%) described that the vaccination series was discontinued because of non-serious AEs. Most reported AEs are non-serious and consistent with pre-licensure safety data. The rabies risk must be carefully considered before vaccine discontinuation.

BACKGROUND Heterologous prime-boost vaccination is a pandemic response strategy utilizing subtype-matched vaccine at pandemic onset followed by strain-matched vaccine once available. Persistence of immune response and safety of influenza A (H5N1) vaccine adjuvanted with adjuvant system containing α-tocopherol and squalene in an oil-in-water emulsion (AS03B) were evaluated. METHODS An open phase 3 active-controlled study (www.clinicaltrials.gov NCT01379937) assessed immunogenicity and reactogenicity of a heterologous booster dose of A/turkey/Turkey/1/2005-H5N1-AS03B in children 3 to

Segun lo establecido por la Organizacion Panamericana de la Salud (OPS), conseguir una alta cobertura de vacunacion es una meta esencial para la Region de las Americas. Es indispensable lograr niveles de cobertura de 95% o mayores para poder alcanzar los objetivos de la OPS de eliminar el sarampion y la rubeola, controlar las enfermedades prevenibles mediante la vacunacion, y hacer perdurar la eliminacion de la poliomielitis en territorio americano. Para poder alcanzar esos niveles, es imprescindible que las estadisticas de vacunacion sean fiables y que las autoridades sanita- rias midan y monitoreen los niveles de cobertura a lo largo del tiempo. Los metodos elegidos por los directores de los programas de vacunacion para calcular la cobertura dependeran de la informacion que haga falta. En general, los directores del Programa Ampliado de Inmunizacion (PAI) necesitaran informacion acerca de la cobertura para poder: 1) determinar la verdadera cobertura en los niveles nacional y local, 2) determinar cuan adecuada es la cobertura en una zona determinada, 3) monitorear las tendencias a lo largo del tiempo, y 4) monitorear las actividades de vacunacion mientras se estan llevando a cabo. Para lograr lo primero -determinar cuales son los niveles verdaderos de cobertura-, los administradores tienen dos opciones: a) valerse de los datos acerca de las dosis administradas (es decir, el numero de dosis de la vacuna que se ha administrado, dividido por la poblacion que debio recibir una dosis) o b) llevar a cabo una encuesta para determinar la cobertura. Para lograr lo segundo -saber si la cobertura en una zona determinada es adecuada (por ej., mayor de 90%)-, se puede realizar un muestreo por lotes para garantizar la calidad (MLGC). El MLGC es una metodologia de encuesta basada en el uso de muestras pequenas que permite determinar si la cobertura en una zona determinada es adecuada o no, pero no sirve para estimar el nivel de cobertura. Para el tercer proposito -monitorear las tendencias a lo largo del tiempo-, se pueden usar los datos correspondientes al numero de dosis administradas. Para lograr el cuarto proposito -determinar si procede vacunar o llevar a cabo una campana de vacunacion u otra actividad afin-, la "herramienta de monitoreo rapido" creada por la OPS es una magnifica solucion. Cada uno de estos metodos posee ventajas y desventajas. Los datos sobre el numero de dosis administradas, mas la herramienta de monitoreo rapido, deben usarse para lograr las metas de vacunacion en las Americas. Ambos metodos son los preferidos actualmente por la OPS para estimar la cobertura de vacunacion.

The region of the Americas has shown extraordinary progress in its fight to interrupt measles transmission. The Pan American Health Organization's recommended strategy includes the following: a 1-time nationwide campaign targeting 1- to 14-year-old children; routine vaccination among 1-year-olds; and nationwide campaigns conducted every 4 years, targeting all 1- to 4-year-olds. Rapid house-to-house monitoring of vaccination and measles surveillance are other essential components of the strategy. During 2001, only 541 cases were confirmed in the region. In 2002, only Venezuela and Colombia had indigenous transmission. After important vaccination efforts in both countries, the last reported case occurred on 20 September 2002, in Venezuela. Since then, no confirmation exists of indigenous measles circulation anywhere else in the region. Nonetheless, important challenges remain, including insufficient coverage during routine and campaign vaccination and inadequate investigation of some cases.

Measles incidence in Bolivia declined after the introduction of campaign strategies in the 1980s. From 1990 to 1993, the peak incidence of measles (59 cases/100,000 population) was in 1992. In 1994, after the goal of interruption of measles transmission was adopted, a national vaccination campaign targeting children

On 8 March 2000 a case of laboratory-confirmed measles was detected in Haiti. Over the ensuing months, an explosive epidemic occurred that spread to 8 of the 9 departments of Haiti, including the nation's capital, Port au Prince. After peaking in the last half of November 2000, the epidemic began a rapid decline. The date of onset for the last confirmed case was 26 September 2001. During the 18 months of the epidemic, 1149 cases were confirmed. To control the epidemic, various strategies were employed, including vaccination campaigns that used fixed posts and door-to-door activities. Critical factors in the success of these campaigns were thorough training and supervision of field staff; a high-quality door-to-door vaccination strategy; multiple visits to homes; and monitoring of vaccine coverage by household during the course of the campaigns.

Since 1994, when the goal of interrupting indigenous measles transmission was adopted, important progress has been made toward the control of measles in the Americas. Thirty-nine (95%) of 41 countries reporting to the Pan American Health Organization (PAHO) conducted catch-up vaccination campaigns during 1989-1995 and follow-up measles campaigns every 4 years. Routine (keep-up) vaccination coverage in the Region increased from 80% in 1994 to 94% in 2000. Measles vaccination coverage ranged between 75% and 99% in 2000 and between 53% and 99% in 2001. As a result, in 2001, the total number of confirmed measles cases reached a record low of 537, 99% lower than the number reported in 1990. In 2002, only Venezuela and Colombia had known indigenous transmission. As of January 2003, no known indigenous measles transmission had occurred in the Region since November 2002. This is due to high political commitment and implementation of PAHO's recommendations, including strengthened supervision and monitoring to improve accountability at the local level.

This study characterizes a measles outbreak which occurred in Ecuador in 2011–2012, analyzing data from 3700 suspected cases of measles reported to Ecuador’s Ministry of Public Health. The study population had a large age range and included 333 confirmed cases of measles. The greatest number of cases were found in the

In a PLOS Medicine Review, Felicity Cutts and colleagues describe the challenges facing the estimation of vaccination coverage in low- and middle-income countries using surveys and recommend ways to improve the measurement of this important public health indicator., Vaccination coverage is an important public health indicator that is measured using administrative reports and/or surveys. The measurement of vaccination coverage in low- and middle-income countries using surveys is susceptible to numerous challenges. These challenges include selection bias and information bias, which cannot be solved by increasing the sample size, and the precision of the coverage estimate, which is determined by the survey sample size and sampling method. Selection bias can result from an inaccurate sampling frame or inappropriate field procedures and, since populations likely to be missed in a vaccination coverage survey are also likely to be missed by vaccination teams, most often inflates coverage estimates. Importantly, the large multi-purpose household surveys that are often used to measure vaccination coverage have invested substantial effort to reduce selection bias. Information bias occurs when a child's vaccination status is misclassified due to mistakes on his or her vaccination record, in data transcription, in the way survey questions are presented, or in the guardian's recall of vaccination for children without a written record. There has been substantial reliance on the guardian's recall in recent surveys, and, worryingly, information bias may become more likely in the future as immunization schedules become more complex and variable. Finally, some surveys assess immunity directly using serological assays. Sero-surveys are important for assessing public health risk, but currently are unable to validate coverage estimates directly. To improve vaccination coverage estimates based on surveys, we recommend that recording tools and practices should be improved and that surveys should incorporate best practices for design, implementation, and analysis.

Background: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barre syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination. Methods: The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach. Results: We found a relative incidence of GBS of 2.42(95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09(95% CI 1.28-3.42) using the meta-analytic approach. Conclusions: This study demonstrates that international collaboration to evaluate serious outcomes using a common protocol is feasible. The significance and consistency of our findings support a conclusion of an association between 2009 H1N1 vaccination and GBS. Given the rarity of the event the relative incidence found does not provide evidence in contradiction to international recommendations for the continued use of influenza vaccines. (C) 2013 Elsevier Ltd. All rights reserved.

Background. An outbreak of pertussis from July, 1993, to April, 1994, in Chicago was investigated to identify potential contributing factors. Methods. Surveillance was enhanced to identify cases. Information from a vaccination coverage survey was used to define a retrospective cohort to estimate vaccine effectiveness of three or more doses of pertussis vaccine. Results. The median age of 218 reported cases was 8 months, 46% had Hispanic surnames and cases were clustered geographically. Vaccination status was known for 173 of 191 (91%) children younger than 6 years of age. Of these 173, 90 (52%) were younger than 7 months, and 35 (20%) children at least 7 months of age had received fewer than 3 doses of pertussis vaccine. Pertussis vaccine effectiveness was 76% (95% confidence interval, 29 to 92). Conclusions. The limited ability of the current pertussis vaccination schedule to protect young infants accounted for 52% of cases, primary vaccine failure accounted for 28% of cases and failure to vaccinate children on time accounted for 20% of cases in young children. Low vaccine effectiveness did not appear to be a contributing factor.

Because young infants are at highest risk for severe pertussis and death and are also too young to have received the minimal protective series of three doses of diphtheria-tetanus-pertussis (DTP) vaccine, we conducted a matched case-control study to assess risk factors for pertussis among young infants during a pertussis outbreak in Chicago in 1993. We enrolled 39 cases7 months of age from a single teaching hospital and 96 controls, individually matched for age, from the well-child clinic at the same hospital. Demographic characteristics, immunization status, and opportunities for disease exposure were analyzed by means of conditional logistic regression. Cases and controls were similarly up to date with their DTP vaccinations (87% and 89%, respectively). Infants of adolescent mothers (matched odds ratio [OR], 6.4; 95% confidence interval [CI], 1.3-41.4) and infants of mothers who sufferedor = 7 days of cough during the child's incubation period (matched OR, 12.0; 95% CI, 1.4 to infinity) were significantly more likely to have pertussis. Young mothers and mothers with a cough lastingor = 7 days may be an important source of pertussis infection for their young infants.