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Summary Background In the USA, COVID-19 vaccines became available in mid-December, 2020, with adults aged 65 years and older among the first groups prioritised for vaccination. We estimated the national-level impact of the initial phases of the US COVID-19 vaccination programme on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 65 years and older. Methods We analysed population-based data reported to US federal agencies on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 50 years and older during the period Nov 1, 2020, to April 10, 2021. We calculated the relative change in incidence among older age groups compared with a younger reference group for pre-vaccination and post-vaccination periods, defined by the week when vaccination coverage in a given age group first exceeded coverage in the reference age group by at least 1%; time lags for immune response and time to outcome were incorporated. We assessed whether the ratio of these relative changes differed when comparing the pre-vaccination and post-vaccination periods. Findings The ratio of relative changes comparing the change in the COVID-19 case incidence ratio over the post-vaccine versus pre-vaccine periods showed relative decreases of 53% (95% CI 50 to 55) and 62% (59 to 64) among adults aged 65 to 74 years and 75 years and older, respectively, compared with those aged 50 to 64 years. We found similar results for emergency department visits with relative decreases of 61% (52 to 68) for adults aged 65 to 74 years and 77% (71 to 78) for those aged 75 years and older compared with adults aged 50 to 64 years. Hospital admissions declined by 39% (29 to 48) among those aged 60 to 69 years, 60% (54 to 66) among those aged 70 to 79 years, and 68% (62 to 73), among those aged 80 years and older, compared with adults aged 50 to 59 years. COVID-19 deaths also declined (by 41%, 95% CI –14 to 69 among adults aged 65–74 years and by 30%, –47 to 66 among those aged ≥75 years, compared with adults aged 50 to 64 years), but the magnitude of the impact of vaccination roll-out on deaths was unclear. Interpretation The initial roll-out of the US COVID-19 vaccination programme was associated with reductions in COVID-19 cases, emergency department visits, and hospital admissions among older adults. Funding None.

Previous infection with SARS-CoV-2 (the virus that causes COVID-19) or COVID-19 vaccination can provide immunity and protection from subsequent SARS-CoV-2 infection and illness. CDC used data from the VISION Network* to examine hospitalizations in adults with COVID-19-like illness and compared the odds of receiving a positive SARS-CoV-2 test result, and thus having laboratory-confirmed COVID-19, between unvaccinated patients with a previous SARS-CoV-2 infection occurring 90-179 days before COVID-19-like illness hospitalization, and patients who were fully vaccinated with an mRNA COVID-19 vaccine 90-179 days before hospitalization with no previous documented SARS-CoV-2 infection. Hospitalized adults aged ≥18 years with COVID-19-like illness were included if they had received testing at least twice: once associated with a COVID-19-like illness hospitalization during January-September 2021 and at least once earlier (since February 1, 2020, and ≥14 days before that hospitalization). Among COVID-19-like illness hospitalizations in persons whose previous infection or vaccination occurred 90-179 days earlier, the odds of laboratory-confirmed COVID-19 (adjusted for sociodemographic and health characteristics) among unvaccinated, previously infected adults were higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine with no previous documented infection (adjusted odds ratio [aOR] = 5.49; 95% confidence interval [CI] = 2.75-10.99). These findings suggest that among hospitalized adults with COVID-19-like illness whose previous infection or vaccination occurred 90-179 days earlier, vaccine-induced immunity was more protective than infection-induced immunity against laboratory-confirmed COVID-19. All eligible persons should be vaccinated against COVID-19 as soon as possible, including unvaccinated persons previously infected with SARS-CoV-2.

Background There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. Methods We conducted a study involving adults (≥50 years of age) with Covid-19–like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients’ vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. Results The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19–associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. Conclusions Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.)

Objective To evaluate if facility-level vaccination after an initial vaccination clinic was independently associated with COVID-19 incidence adjusted for other factors in January 2021 among nursing home residents. Design Ecological analysis of data from the CDC's National Healthcare Safety Network (NHSN) and from the CDC's Pharmacy Partnership for Long-Term Care Program. Setting and Participants CMS-certified nursing homes participating in both NHSN and the Pharmacy Partnership for Long-Term Care Program. Methods A multivariable, random intercepts, negative binomial model was applied to contrast COVID-19 incidence rates among residents living in facilities with an initial vaccination clinic during the week ending January 3, 2021 (n = 2843), vs those living in facilities with no vaccination clinic reported up to and including the week ending January 10, 2021 (n = 3216). Model covariates included bed size, resident SARS-CoV-2 testing, staff with COVID-19, cumulative COVID-19 among residents, residents admitted with COVID-19, community county incidence, and county social vulnerability index (SVI). Results In December 2020 and January 2021, incidence of COVID-19 among nursing home residents declined to the lowest point since reporting began in May, diverged from the pattern in community cases, and began dropping before vaccination occurred. Comparing week 3 following an initial vaccination clinic vs week 2, the adjusted reduction in COVID-19 rate in vaccinated facilities was 27% greater than the reduction in facilities where vaccination clinics had not yet occurred (95% confidence interval: 14%-38%, P Conclusions and Implications Vaccination of residents contributed to the decline in COVID-19 incidence in nursing homes; however, other factors also contributed. The decline in COVID-19 was evident prior to widespread vaccination, highlighting the benefit of a multifaced approach to prevention including continued use of recommended screening, testing, and infection prevention practices as well as vaccination to keep residents in nursing homes safe.

Nursing home and long-term care facility residents live in congregate settings and are often elderly and frail, putting them at high risk for infection with SARS-CoV-2, the virus that causes COVID-19, and severe COVID-19-associated outcomes; therefore, this population was prioritized for early vaccination in the United States (1). Following rapid distribution and administration of the mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) under an Emergency Use Authorization by the Food and Drug Administration (2), observational studies among nursing home residents demonstrated vaccine effectiveness (VE) ranging from 53% to 92% against SARS-CoV-2 infection (3-6). However, concerns about the potential for waning vaccine-induced immunity and the recent emergence of the highly transmissible SARS-CoV-2 B.1.617.2 (Delta) variant† highlight the need to continue to monitor VE (7). Weekly data reported by the Centers for Medicaid & Medicare (CMS)-certified skilled nursing facilities or nursing homes to CDC's National Healthcare Safety Network (NHSN)§ were analyzed to evaluate effectiveness of full vaccination (2 doses received ≥14 days earlier) with any of the two currently authorized mRNA COVID-19 vaccines during the period soon after vaccine introduction and before the Delta variant was circulating (pre-Delta [March 1-May 9, 2021]), and when the Delta variant predominated¶ (Delta [June 21-August 1, 2021]). Using 17,407 weekly reports from 3,862 facilities from the pre-Delta period, adjusted effectiveness against infection for any mRNA vaccine was 74.7% (95% confidence interval [CI] = 70.0%-78.8%). Analysis using 33,160 weekly reports from 11,581 facilities during an intermediate period (May 10-June 20) found that the adjusted effectiveness was 67.5% (95% CI = 60.1%-73.5%). Analysis using 85,593 weekly reports from 14,917 facilities during the Delta period found that the adjusted effectiveness was 53.1% (95% CI = 49.1%-56.7%). Effectiveness estimates were similar for Pfizer-BioNTech and Moderna vaccines. These findings indicate that mRNA vaccines provide protection against SARS-CoV-2 infection among nursing home residents; however, VE was lower after the Delta variant became the predominant circulating strain in the United States. This analysis assessed VE against any infection, without being able to distinguish between asymptomatic and symptomatic presentations. Additional evaluations are needed to understand protection against severe disease in nursing home residents over time. Because nursing home residents might remain at some risk for SARS-CoV-2 infection despite vaccination, multiple COVID-19 prevention strategies, including infection control, testing, and vaccination of nursing home staff members, residents, and visitors, are critical. An additional dose of COVID-19 vaccine might be considered for nursing home and long-term care facility residents to optimize a protective immune response.

ObjectiveTo determine the difference in rate of weight gain from birth to 5 years based on exposure to maternal group B streptococcal (GBS) intrapartum antibiotic prophylaxis (IAP).DesignRetrospective cohort study of 13 804 infants.SettingTwo perinatal centres and a primary paediatric care network in Philadelphia.ParticipantsTerm infants born 2007–2012, followed longitudinally from birth to 5 years of age.ExposuresGBS IAP defined as penicillin, ampicillin, cefazolin, clindamycin or vancomycin administered ≥4 hours prior to delivery to the mother. Reference infants were defined as born to mothers without (vaginal delivery) or with other (caesarean delivery) intrapartum antibiotic exposure.OutcomesDifference in rate of weight change from birth to 5 years was assessed using longitudinal rate regression. Analysis was a priori stratified by delivery mode and adjusted for relevant covariates.ResultsGBS IAP was administered to mothers of 2444/13 804 (17.7%) children. GBS IAP-exposed children had a significantly elevated rate of weight gain in the first 5 years among vaginally-born (adjusted rate difference 1.44% (95% CI 0.3% to 2.6%)) and caesarean-born (3.52% (95% CI 1.9% to 5.2%)) children. At 5 years, the rate differences equated to an additional 0.24 kg among vaginally-born children and 0.60 kg among caesarean-born children.ConclusionGBS-specific IAP was associated with a modest increase in rate of early childhood weight gain. GBS IAP is an effective intervention to prevent perinatal GBS disease-associated morbidity and mortality. However, these findings highlight the need to better understand effects of intrapartum antibiotic exposure on childhood growth and support efforts to develop alternate prevention strategies.

Psittacosis is typically a mild febrile respiratory illness caused by infection with the bacterium Chlamydia psittaci and usually transmitted to humans by infected birds (1). On average, 11 psittacosis cases per year were reported in the United States during 2000-2017. During August-October 2018, the largest U.S. psittacosis outbreak in 30 years (82 cases identified*) occurred in two poultry slaughter plants, one each in Virginia and Georgia, that shared source farms (2). CDC used C. psittaci real-time polymerase chain reaction (PCR) to test 54 human specimens from this outbreak. This was the largest number of human specimens from a single outbreak ever tested for C. psittaci using real-time PCR, which is faster and more sensitive than commercially available serologic tests. This represented a rare opportunity to assess the utility of multiple specimen types for real-time PCR detection of C. psittaci. C. psittaci was detected more frequently in lower respiratory specimens (59% [10 of 17]) and stool (four of five) than in upper respiratory specimens (7% [two of 28]). Among six patients with sputum and nasopharyngeal swabs tested, C. psittaci was detected only in sputum in five patients. Cycle threshold (Ct) values suggested bacterial load was higher in lower respiratory specimens than in nasopharyngeal swabs. These findings support prioritizing lower respiratory specimens for real-time PCR detection of C. psittaci. Stool specimens might also have utility for diagnosis of psittacosis.

Residents of long-term care facilities (LTCFs), particularly those in skilled nursing facilities (SNFs), have experienced disproportionately high levels of COVID-19-associated morbidity and mortality and were prioritized for early COVID-19 vaccination (1,2). However, this group was not included in COVID-19 vaccine clinical trials, and limited postauthorization vaccine effectiveness (VE) data are available for this critical population (3). It is not known how well COVID-19 vaccines protect SNF residents, who typically are more medically frail, are older, and have more underlying medical conditions than the general population (1). In addition, immunogenicity of the Pfizer-BioNTech vaccine was found to be lower in adults aged 65-85 years than in younger adults (4). Through the CDC Pharmacy Partnership for Long-Term Care Program, SNF residents and staff members in Connecticut began receiving the Pfizer-BioNTech COVID-19 vaccine on December 18, 2020 (5). Administration of the vaccine was conducted during several on-site pharmacy clinics. In late January 2021, the Connecticut Department of Public Health (CT DPH) identified two SNFs experiencing COVID-19 outbreaks among residents and staff members that occurred after each facility's first vaccination clinic. CT DPH, in partnership with CDC, performed electronic chart review in these facilities to obtain information on resident vaccination status and infection with SARS-CoV-2, the virus that causes COVID-19. Partial vaccination, defined as the period from >14 days after the first dose through 7 days after the second dose, had an estimated effectiveness of 63% (95% confidence interval [CI] = 33%-79%) against SARS-CoV-2 infection (regardless of symptoms) among residents within these SNFs. This is similar to estimated effectiveness for a single dose of the Pfizer-BioNTech COVID-19 vaccine in adults across a range of age groups in noncongregate settings (6) and suggests that to optimize vaccine impact among this population, high coverage with the complete 2-dose series should be recommended for SNF residents and staff members.

Background Intrapartum antibiotic prophylaxis (IAP) reduces a newborn’s risk of group B streptococcal infection (GBS) but may lead to an increased childhood body mass index (BMI). Methods This was a retrospective cohort study of infants (n = 223 431) born 2007–2015 in an integrated healthcare system. For vaginal delivery, we compared children exposed to GBS-IAP and to any other type or duration of intrapartum antibiotics to no antibiotic exposure. For cesarean delivery, we compared children exposed to GBS-IAP to those exposed to all other intrapartum antibiotics, including surgical prophylaxis. BMI over 5 years was compared using nonlinear multivariate models with B-spline functions, stratified by delivery mode and adjusted for demographics, maternal factors, breastfeeding, and childhood antibiotic exposure. Results In vaginal deliveries, GBS-IAP was associated with higher BMI from 0.5 to 5.0 years of age compared to no antibiotics (P Conclusions GBS-IAP was associated with a small but sustained increase in BMI starting at very early age. This association highlights the need to better understand the effects of perinatal antibiotic exposure on childhood health.

Background The prioritization of U.S. health care personnel for early receipt of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), allowed for the evaluation of the effectiveness of these new vaccines in a real-world setting. Methods We conducted a test-negative case–control study involving health care personnel across 25 U.S. states. Cases were defined on the basis of a positive polymerase-chain-reaction (PCR) or antigen-based test for SARS-CoV-2 and at least one Covid-19–like symptom. Controls were defined on the basis of a negative PCR test for SARS-CoV-2, regardless of symptoms, and were matched to cases according to the week of the test date and site. Using conditional logistic regression with adjustment for age, race and ethnic group, underlying conditions, and exposures to persons with Covid-19, we estimated vaccine effectiveness for partial vaccination (assessed 14 days after receipt of the first dose through 6 days after receipt of the second dose) and complete vaccination (assessed ≥7 days after receipt of the second dose). Results The study included 1482 case participants and 3449 control participants. Vaccine effectiveness for partial vaccination was 77.6% (95% confidence interval [CI], 70.9 to 82.7) with the BNT162b2 vaccine (Pfizer–BioNTech) and 88.9% (95% CI, 78.7 to 94.2) with the mRNA-1273 vaccine (Moderna); for complete vaccination, vaccine effectiveness was 88.8% (95% CI, 84.6 to 91.8) and 96.3% (95% CI, 91.3 to 98.4), respectively. Vaccine effectiveness was similar in subgroups defined according to age (

Evaluations of vaccine effectiveness (VE) are important to monitor as coronavirus disease 2019 (COVID-19) vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19–like illness or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, the VE of messenger RNA vaccines against COVID-19 was 91% (95% confidence interval, 83%–95%) for full vaccination and 75% (55%–87%) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care., With the test-negative design used to evaluate protection from messenger RNA vaccines, vaccine effectiveness against coronavirus disease 2019 among outpatients aged ≥16 years was 91% (95% confidence interval, 83%–95%) for full vaccination and 75% (55%–87%) for partial vaccination.

BackgroundPrisons and jails are high-risk settings for COVID-19 transmission, morbidity, and mortality. COVID-19 vaccines may substantially reduce these risks, but evidence is needed of their effectiveness for incarcerated people, who are confined in large, risky congregate settings.MethodsWe conducted a retrospective cohort study to estimate effectiveness of mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), against confirmed SARS-CoV-2 infections among incarcerated people in California prisons from December 22, 2020 through March 1, 2021. The California Department of Corrections and Rehabilitation provided daily data for all prison residents including demographic, clinical, and carceral characteristics, as well as COVID-19 testing, vaccination status, and outcomes. We estimated vaccine effectiveness using multivariable Cox models with time-varying covariates that adjusted for resident characteristics and infection rates across prisons.FindingsAmong 60,707 residents in the cohort, 49% received at least one BNT162b2 or mRNA-1273 dose during the study period. Estimated vaccine effectiveness was 74% (95% confidence interval [CI], 64−82%) from day 14 after first dose until receipt of second dose and 97% (95% CI, 88−99%) from day 14 after second dose. Effectiveness was similar among the subset of residents who were medically vulnerable (74% [95% CI, 62−82%] and 92% [95% CI, 74−98%] from 14 days after first and second doses, respectively), as well as among the subset of residents who received the mRNA-1273 vaccine (71% [95% CI, 58−80%] and 96% [95% CI, 67−99%]).ConclusionsConsistent with results from randomized trials and observational studies in other populations, mRNA vaccines were highly effective in preventing SARS-CoV-2 infections among incarcerated people. Prioritizing incarcerated people for vaccination, redoubling efforts to boost vaccination and continuing other ongoing mitigation practices are essential in preventing COVID-19 in this disproportionately affected population.FundingHorowitz Family Foundation, National Institute on Drug Abuse, Centers for Disease Control and Prevention, National Science Foundation, Open Society Foundation, Advanced Micro Devices.

Clinical trials of COVID-19 vaccines currently authorized for emergency use in the United States (Pfizer-BioNTech, Moderna, and Janssen [Johnson & Johnson]) indicate that these vaccines have high efficacy against symptomatic disease, including moderate to severe illness (1-3). In addition to clinical trials, real-world assessments of COVID-19 vaccine effectiveness are critical in guiding vaccine policy and building vaccine confidence, particularly among populations at higher risk for more severe illness from COVID-19, including older adults. To determine the real-world effectiveness of the three currently authorized COVID-19 vaccines among persons aged ≥65 years during February 1-April 30, 2021, data on 7,280 patients from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed with vaccination coverage data from state immunization information systems (IISs) for the COVID-NET catchment area (approximately 4.8 million persons). Among adults aged 65-74 years, effectiveness of full vaccination in preventing COVID-19-associated hospitalization was 96% (95% confidence interval [CI]=94%-98%) for Pfizer-BioNTech, 96% (95% CI=95%-98%) for Moderna, and 84% (95% CI=64%-93%) for Janssen vaccine products. Effectiveness of full vaccination in preventing COVID-19-associated hospitalization among adults aged ≥75 years was 91% (95% CI=87%-94%) for Pfizer-BioNTech, 96% (95% CI=93%-98%) for Moderna, and 85% (95% CI=72%-92%) for Janssen vaccine products. COVID-19 vaccines currently authorized in the United States are highly effective in preventing COVID-19-associated hospitalizations in older adults. In light of real-world data demonstrating high effectiveness of COVID-19 vaccines among older adults, efforts to increase vaccination coverage in this age group are critical to reducing the risk for COVID-19-related hospitalization.

Evaluations of vaccine effectiveness (VE) are important to monitor as COVID-19 vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or SARS-CoV-2 testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, VE of mRNA vaccines against COVID-19 was 91% (95% CI: 83-95) for full vaccination and 75% (95% CI: 55-87) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.

Recent studies have provided key information about SARS-CoV-2 vaccines’ efficacy and effectiveness (VE). One important question that remains is whether the protection conferred by vaccines wanes over time. However, estimates over time are subject to bias from differential depletion of susceptibles between vaccinated and unvaccinated groups. Here we examine the extent to which biases occur under different scenarios and assess whether serologic testing has the potential to correct this bias. By identifying non-vaccine antibodies, these tests could identify individuals with prior infection. We find in scenarios with high baseline VE, differential depletion of susceptibles creates minimal bias in VE estimates, suggesting that any observed declines are likely not due to spurious waning alone. However, if baseline VE is lower, the bias for leaky vaccines (that reduce individual probability of infection given contact) is larger and should be corrected by excluding individuals with past infection if the mechanism is known to be leaky. Conducting analyses both unadjusted and adjusted for past infection could give lower and upper bounds for the true VE. Studies of VE should therefore enroll individuals regardless of prior infection history but also collect information, ideally through serologic testing, on this critical variable.

BackgroundAs SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes.MethodsIn a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2.ResultsAmong 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%).ConclusionDuring March–May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

Background As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination coverage increases in the United States, there is a need to understand the real-world effectiveness against severe coronavirus disease 2019 (COVID-19) and among people at increased risk for poor outcomes. Methods In a multicenter case-control analysis of US adults hospitalized March 11–May 5, 2021, we evaluated vaccine effectiveness to prevent COVID-19 hospitalizations by comparing odds of prior vaccination with a messenger RNA (mRNA) vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with COVID-19 and hospital-based controls who tested negative for SARS-CoV-2. Results Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B0.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of 2 vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% confidence interval [CI], 80.7–91.3). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18–49 years (97.4%; 95% CI, 79.3–9.7). Among 45 patients with vaccine-breakthrough COVID hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI,20.8–82.6) than without immunosuppression (91.3%; 95% CI, 85.6–94.8). Conclusion During March–May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing COVID-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

BACKGROUND: Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands.METHODS: For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts.FINDINGS: 2258 children-1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)-were identified to have iGBS disease and followed up for a median of 14 years (IQR 7-18) in Denmark and 9 years (6-11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78-9·35] for Denmark and 6·73 [3·76-12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44-2·18]) and the Netherlands (2·28 [1·64-3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79-2·09], pINTERPRETATION: iGBS disease, especially meningitis, was associated with increased mortality and a higher risk of NDIs in later childhood. This previously unquantified burden underlines the case for a maternal GBS vaccine, and the need to track and provide care for affected survivors of iGBS disease.FUNDING: The Bill & Melinda Gates Foundation.TRANSLATIONS: For the Dutch and Danish translations of the abstract see Supplementary Materials section.

Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.

Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection.

The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) was a randomized, controlled trial of rVSVΔG-ZEBOV-GP vaccine in healthcare and frontline workers during the 2014–2016 Ebola epidemic. Overall safety findings have been previously reported; there were no vaccine-related serious adverse events (SAEs). Here we describe the safety monitoring system established for STRIVE and the health conditions that resulted in reported SAEs, as well as factors affecting SAE incidence. Participants were randomized to immediate (≤7 days) or deferred (18–24 weeks later) vaccination and were monitored for safety for 6 months (immediate-vaccinated group) or until vaccination (deferred [unvaccinated] group). Once vaccinated, the latter group was termed crossover-vaccinated and monitored for 6 additional months. Of the 8577 STRIVE participants with safety follow-up data, 4172 were in the immediate-vaccinated group and 4398 were in the unvaccinated group, of whom 3787 received crossover vaccination. Overall, 143 SAEs were reported among 132 participants. Of the 143 SAEs, 130 (90.9%) resulted in hospitalization, and 24 (18.2%) participants with an SAE died. Infections were the most common SAEs; malaria was the most common single diagnosis and the most common cause of death. STRIVE built local capacity for vaccine safety monitoring in future clinical trials and research and in the national immunization program. This information about serious health conditions that resulted in hospitalization or death among a population of relatively young, healthy adults in Sierra Leone could help inform improved delivery of preventive and therapeutic health services. Clinical Trials Registration ClinicalTrials.gov [{"type":"clinical-trial","attrs":{"text":"NCT02378753","term_id":"NCT02378753"}}NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

BackgroundStreptococcus agalactiae(Group B Streptococcus, GBS) serotypes, sequence types, and antimicrobial resistance profile vary across different geographic locations affecting disease patterns in newborns. These differences are important considerations for vaccine development efforts and data from large countries in Africa is limited. The aim of this study was to determine serotypes and genotypes of GBS isolates from pregnant women and their newborns in Ethiopia.MethodsA hospital based cross-sectional study was conducted at three hospitals in Ethiopia from June 2014 to September 2015. Out of 225 GBS isolates, 121 GBS were recovered, confirmed and characterized at CDC’s Streptococcus Laboratory using conventional microbiology methods and whole genome sequencing.ResultsOf the 121 isolates, 87 were from rectovaginal samples of pregnant women, 32 from different body parts of their newborns and 2 from blood of newborns with suspected sepsis. There were 25 mother-infant pairs and 24 pairs had concordant strains. The most prevalent serotypes among mothers and/or their babies were II, Ia and V (41.5, 20.6, 19.5 and 40.6%, 25 and 15.6%, respectively). Multilocus sequence typing (MLST) on 83 isolates showed ST10 (24; 28.9%) and ST2 (12; 14.5%) as most predominant sequence types. All GBS strains were susceptible to penicillin, cefotaxime and vancomycin, which correlated to the presence of wildtype PBP2x types and the lack of known vancomycin-resistance genes. Tetracycline resistance was high (73; 88%, associated primarily withtetM, but alsotetOandtetL). Five isolates (6%) were resistant to erythromycin and clindamycin and 3 isolates were fluoroquinolone-resistant, containing associated mutations ingyrAandparCgenes. All isolates were positive for one of four homologous Alpha/Rib family determinants and 1–2 of the three main pilus types.ConclusionsPredominant serotypes were II, Ia, and V. A limited number of clonal types were identified with two STs accounting for about half of the isolates. All strains collected in this study were susceptible to beta-lactam antibiotics and vancomycin. Typical of most GBS, these isolates were positive for single alpha-like family protein, serine-rich repeat gene, as well as 1–2 pilus determinants.

Highlights • There is a major public health need for GBS vaccines for maternal immunization. • Important obstacles lie in the way of a pivotal clinical efficacy trial for licensure. • A vaccine development pathway based on an immune correlate of protection is envisaged. • Key considerations and priority activities for success are presented, based on WHO consultations., The development of a group B Streptococcus (GBS) vaccine for maternal immunization constitutes a global public health priority, to prevent GBS-associated early life invasive disease, stillbirth, premature birth, maternal sepsis, adverse neurodevelopmental consequences, and to reduce perinatal antibiotic use. Sample size requirements for the conduct of a randomized placebo-controlled trial to assess vaccine efficacy against the most relevant clinical endpoints, under conditions of appropriate ethical standards of care, constitute a significant obstacle on the pathway to vaccine availability. Alternatively, indirect evidence of protection based on immunologic data from vaccine and sero-epidemiological studies, complemented by data from opsonophagocytic in vitro assays and animal models, could be considered as pivotal data for licensure, with subsequent confirmation of effectiveness against disease outcomes in post-licensure evaluations. Based on discussions initiated by the World Health Organization we present key considerations about the potential role of correlates of protection towards an accelerated pathway for GBS vaccine licensure and wide scale use. Priority activities to support progress to regulatory and policy decision are outlined.

The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSV∆G-ZEBOV-GP vaccine, was conducted during an unprecedented Ebola epidemic. More than 8600 eligible healthcare and frontline response workers were individually randomized to immediate (within 7 days) or deferred (within 18–24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola virus infection. Key challenges included limited infrastructure to support trial activities, unreliable electricity, and staff with limited clinical trial experience. Study staff made substantial infrastructure investments, including renovation of enrollment sites, laboratories, and government cold chain facilities, and imported equipment to store and transport vaccine at ≤−60oC. STRIVE built capacity by providing didactic and practical research training to >350 staff, which was reinforced with daily review and feedback meetings. The operational challenges of safety follow-up were addressed by issuing mobile telephones to participants, making home visits, and establishing a nurse triage hotline. Before the Ebola outbreak, Sierra Leone had limited infrastructure and staff to conduct clinical trials. Without interfering with the outbreak response, STRIVE responded to an urgent need and helped build this capacity. Clinical Trials Registration. ClinicalTrials.gov [{"type":"clinical-trial","attrs":{"text":"NCT02378753","term_id":"NCT02378753"}}NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

The West Africa Ebola epidemic stimulated rapid implementation of Ebola vaccine trials in the 3 highly affected countries. In Sierra Leone, we studied the recombinant vesicular stomatitis virus Ebola vaccine (rVSV∆G-ZEBOV-GP) safety and efficacy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) was a randomized, unblinded Phase 2/3 trial with phased vaccine introduction, no placebo, and concurrent evaluation of vaccine safety and efficacy. Healthcare and frontline response workers in 5 districts were randomized to immediate or deferred (18–24 weeks later) vaccination and followed for 6 months postvaccination. We enrolled 8651 participants from April through August 2015; 7998 were vaccinated. No participants developed Ebola virus disease so an efficacy assessment was not possible. Overall, 132 (1.5%) participants experienced serious adverse events (SAEs); none were vaccine-related. In a detailed safety substudy (N = 436), vaccinated participants reported significantly more systemic adverse events (AEs) within 7 days than unvaccinated participants including fever higher than 38°C (20.5% vs 3.9%), headache (71.2% vs 22.1%), fatigue (50.7% vs 10.4%), and joint pain (31.7% vs 6.5%); most AEs were mild to moderate severity and resolved within 5 days. During days 5-28, vaccinated participants more commonly reported joint pain (17.0% vs 4.8%) and rash (7.8% vs 1.7%) (P

The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE), a clinical trial of the investigational recombinant vesicular stomatitis virus–based Ebola virus vaccine (rVSV∆ZEBOV-GP; Merck), provided an opportunity to assess health conditions in a cohort of healthy Sierra Leonean adults before vaccination. Of the 8793 healthcare and frontline Ebola response workers screened for study enrollment, 7 (0.1%) self-reported human immunodeficiency virus infection or another significant immunodeficiency disorder and 11 of 3190 (0.3%) women 18–49 years old had a positive urine pregnancy test. Of the 440 participants included in a safety substudy, 124 (28.2%) reported at least 1 medical condition at baseline, most commonly drug hypersensitivity (11.6%), arthralgia (3.9%), arthropathy (2.7%), or gastric (3.0%) or peptic (2.7%) ulcer disease. We calculated the incidence per 100 person-years (PY) and 95% confidence intervals (CIs) of new medical conditions among the 4297 participants followed for 18–24 weeks from enrollment to scheduled vaccination. The most commonly reported conditions were headache (32.4 PY [95% CI, 29.7–35.3 PY]), pain (unspecified) (17.3 PY [95% CI, 15.4–19.4 PY]), arthralgia (9.3 PY [95% CI, 7.9–10.8 PY]), and abdominal pain (9.1 PY [95% CI, 7.7–10.7 PY]). Nasopharyngitis (7.0 PY [95% CI, 5.8–8.4 PY]) and malaria (1.9 PY [95% CI, 1.3–2.7 PY]) were the most commonly reported infectious conditions. Several cases of hypertension, diabetes mellitus, and cancer were also reported. Clinical Trials Registration ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Perinatal group B Streptococcus (GBS) disease prevention guidelines in 2010 allowed for processing of screening specimens by nucleic acid amplification tests (NAATs); however, the extent of NAAT use is unknown. A 2016 laboratory survey sent to 10 surveillance sites found that 18.7% of responding laboratories offered NAAT for GBS screening (antenatal only: 7.3%; intrapartum only: 4.1%; both: 3.4%).

Complications of preterm birth are the leading cause of deaths in children aged, Background Preterm birth complications are the leading cause of deaths among children

Background Early-onset group B streptococcal disease (EOGBS) occurs in neonates (days 0–6) born to pregnant women who are rectovaginally colonized with group B Streptococcus (GBS), but the risk of EOGBS from vertical transmission has not been systematically reviewed. This article, the seventh in a series on the burden of GBS disease, aims to estimate this risk and how it varies with coverage of intrapartum antibiotic prophylaxis (IAP), used to reduce the incidence of EOGBS. Methods We conducted systematic reviews (Pubmed/Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on maternal GBS colonization and neonatal outcomes. We included articles with ≥200 GBS colonized pregnant women that reported IAP coverage. We did meta-analyses to determine pooled estimates of risk of EOGBS, and examined the association in risk of EOGBS with IAP coverage. Results We identified 30 articles including 20328 GBS-colonized pregnant women for inclusion. The risk of EOGBS in settings without an IAP policy was 1.1% (95% confidence interval [CI], .6%–1.5%). As IAP increased, the risk of EOGBS decreased, with a linear association. Based on linear regression, the risk of EOGBS in settings with 80% IAP coverage was predicted to be 0.3% (95% CI, 0–.9). Conclusions The risk of EOGBS among GBS-colonized pregnant women, from this first systematic review, is consistent with previous estimates from single studies (1%–2%). Increasing IAP coverage was linearly associated with decreased risk of EOGBS disease.

Background Neonatal encephalopathy (NE) is a leading cause of child mortality and longer-term impairment. Infection can sensitize the newborn brain to injury; however, the role of group B streptococcal (GBS) disease has not been reviewed. This paper is the ninth in an 11-article series estimating the burden of GBS disease; here we aim to assess the proportion of GBS in NE cases. Methods We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups reporting GBS-associated NE. Meta-analyses estimated the proportion of GBS disease in NE and mortality risk. UK population-level data estimated the incidence of GBS-associated NE. Results Four published and 25 unpublished datasets were identified from 13 countries (N = 10436). The proportion of NE associated with GBS was 0.58% (95% confidence interval [CI], 0.18%–.98%). Mortality was significantly increased in GBS-associated NE vs NE alone (risk ratio, 2.07 [95% CI, 1.47–2.91]). This equates to a UK incidence of GBS-associated NE of 0.019 per 1000 live births. Conclusions The consistent increased proportion of GBS disease in NE and significant increased risk of mortality provides evidence that GBS infection contributes to NE. Increased information regarding this and other organisms is important to inform interventions, especially in low- and middle-resource contexts.

Background Legionnaires’ disease, a severe pneumonia, is typically acquired through inhalation of aerosolized water containing Legionella bacteria. Legionella can grow in the complex water systems of buildings, including health care facilities. Effective water management programs could prevent the growth of Legionella in building water systems. Methods Using national surveillance data, Legionnaires’ disease cases were characterized from the 21 jurisdictions (20 U.S. states and one large metropolitan area) that reported exposure information for ≥90% of 2015 Legionella infections. An assessment of whether cases were health care–associated was completed; definite health care association was defined as hospitalization or long-term care facility residence for the entire 10 days preceding symptom onset, and possible association was defined as any exposure to a health care facility for a portion of the 10 days preceding symptom onset. All other Legionnaires’ disease cases were considered unrelated to health care. Results A total of 2,809 confirmed Legionnaires’ disease cases were reported from the 21 jurisdictions, including 85 (3%) definite and 468 (17%) possible health care–associated cases. Among the 21 jurisdictions, 16 (76%) reported 1–21 definite health care–associated cases per jurisdiction. Among definite health care–associated cases, the majority (75, 88%) occurred in persons aged ≥60 years, and exposures occurred at 72 facilities (15 hospitals and 57 long-term care facilities). The case fatality rate was 25% for definite and 10% for possible health care–associated Legionnaires’ disease. Conclusions and Implications for Public Health Practice Exposure to Legionella from health care facility water systems can result in Legionnaires’ disease. The high case fatality rate of health care–associated Legionnaires’ disease highlights the importance of case prevention and response activities, including implementation of effective water management programs and timely case identification.

Background In the United States, approximately 30,000 invasive group B Streptococcus (iGBS) infections occur annually; beta-lactam antibiotics (BL) are the first choice for prevention in young infants and treatment in all age groups. We obtained phenotypic and genotypic data for iGBS isolates from U.S. population-based surveillance sites to describe the emergence and characteristics of strains with reduced beta-lactam susceptibility (RS) over a 20-year period. Methods We analyzed RS iGBS isolates from eight Active Bacterial Core surveillance sites from 1998–2017. Through 2014, minimum inhibitory concentrations (MIC) for six BL were determined by broth microdilution, followed by whole genome sequencing (WGS) of RS isolates exceeding pre-defined breakpoints (Table 1). In 2015, WGS and MIC testing were performed for all isolates. After 2015, all isolates underwent WGS. MIC testing was continued on approximately 25% of isolates; otherwise, only those with modified penicillin binding protein (PBP) 2x transpeptidase amino acid sequence types or suboptimal WGS (< 1 % of isolates) underwent MIC testing. Clinical information on RS cases was abstracted from medical charts. Results Of 26,058 out of 27,269 iGBS isolates (95.6%) tested to date, 107 (0.4%) exhibited RS, increasing from 0% in 1998 to a peak of 1.1% in 2016 (P< 0.05 for trend) (Figure 1). Seven (6.5%) RS strains were from infants aged < 90 days; the rest were from adults aged ≥30 years (Table 2). RS strains consisted of 52 PBP2x types with diverse susceptibility patterns (Table 1). Seven RS strains (6.5%) had wild-type (non-modified) PBP2x; all met the RS criteria based on a single cephalosporin with a confirmed (repeated) MIC value at the break point (Table 1). Compared to non-RS strains, RS strains were more common in patients who presented with cellulitis and osteomyelitis and with underlying conditions such as diabetes or chronic skin breakdown (Table 2). Of 82 (85.4%) patients with RS strains and additional clinical information, 8.3% had known prior GBS infection; 26.8% had known BL exposure in the preceding year. Conclusion Preliminary results show that RS increased in recent years; strains RS to penicillin and ampicillin remain low. Variable pbp2x mutations have emerged and predominant strains have not yet been identified. Disclosures Nisha B. Alden, MPH, CDC (Grant/Research Support) Lee Harrison, MD, Dynavax (Consultant)GSK (Consultant)Merck (Consultant)OMVax (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant)

BackgroundGroup B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development.MethodsUsing whole genome sequencing, a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6340 invasive GBS isolates recovered during 2015–2017 through population-based Active Bacterial Core surveillance (ABCs) in 8 states.ResultsSix serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in 11 clonal complexes (CCs) comprised of multilocus sequence types identical or closely related to sequence types 1, 8, 12, 17, 19, 22, 23, 28, 88, 452, and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with nonsusceptibility to 1 or more β-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin nonsusceptible (minimum inhibitory concentration = 2 µg/mL). Nearly all isolates possessed capsule genes, 1–2 of the 3 main pilus gene clusters, and 1 of 4 homologous alpha/Rib family determinants. Presence of the hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed.ConclusionsThis first comprehensive, population-based quantitation of strain features in the United States suggests that current vaccine candidates should have good coverage. The β-lactams remain appropriate for first-line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring.

Group B Streptococcus (GBS) is an important cause of disease in young infants, stillbirths, pregnant and post-partum women. GBS vaccines for maternal immunization are in development aiming to reduce this burden. Standardisation of case definitions and ascertainment methodologies for GBS disease is needed to support future trials of maternal GBS vaccines. Considerations presented here may also serve to promote consistency in observational studies and surveillance, to better establish disease burden. The World Health Organization convened a working group to provide consensus guidance for case ascertainment and case definitions of GBS disease in stillbirths, infants, pregnant and post-partum women, with feedback sought from external stakeholders. In intervention studies, case capture and case ascertainment for GBS disease should be based on antenatal recruitment of women, with active follow-up, systematic clinical assessment, standardised sampling strategies and optimised laboratory methods. Confirmed cases of invasive GBS disease in stillbirths or infants should be included in a primary composite endpoint for vaccine efficacy studies, with GBS cultured from a usually sterile body site (may be post-mortem). For additional endpoints, or observational studies, confirmed cases of GBS sepsis in pregnant and post-partum women should be assessed. Culture independent diagnostic tests (CIDTs) may detect additional presumed cases, however, the use of these diagnostics needs further evaluation. Efficacy of vaccination against maternal and neonatal GBS colonisation, and maternal GBS urinary tract infection could be included as additional, separate, endpoints and/or in observational studies. Whilst the focus here is on specific GBS disease outcomes, intervention studies also present an opportunity to establish the contribution of GBS across adverse perinatal outcomes, including all-cause stillbirth, preterm birth and neonatal encephalopathy.

IMPORTANCE: Group B Streptococcus (GBS) is an important cause of invasive bacterial disease. Previous studies have shown a substantial and increasing burden of GBS infections among nonpregnant adults, particularly older adults and those with underlying medical conditions. OBJECTIVE: To update trends of invasive GBS disease among US adults using population-based surveillance data. DESIGN, SETTING, AND PARTICIPANTS: In this population-based surveillance study, a case was defined as isolation of GBS from a sterile site between January 1, 2008, and December 31, 2016. Demographic and clinical data were abstracted from medical records. Rates were calculated using US Census data. Antimicrobial susceptibility testing and serotyping were performed on a subset of isolates. Case patients were residents of 1 of 10 catchment areas of the Active Bacterial Core surveillance (ABCs) network, representing approximately 11.5% of the US adult population. Patients were included in the study if they were nonpregnant, were 18 years or older, were residents of an ABCs catchment site, and had a positive GBS culture from a normally sterile body site. MAIN OUTCOMES AND MEASURES: Trends in GBS cases overall and by demographic characteristics (sex, age, and race), underlying clinical conditions of patients, and isolate characteristics are described. RESULTS: The ABCs network detected 21 250 patients with invasive GBS among nonpregnant adults from 2008 through 2016. The GBS incidence in this population increased from 8.1 cases per 100 000 population in 2008 to 10.9 in 2016 (P = .002 for trend). There were 3146 cases reported in 2016 (59% male; median age, 64 years; age range, 18-103 years). The GBS incidence was higher among men than women and among blacks than whites and increased with age. Projected to the US population, an estimated 27 729 cases of invasive disease and 1541 deaths occurred in the United States in 2016. Ninety-five percent of cases in 2016 occurred in someone with at least 1 underlying condition, most commonly obesity (53.9%) and diabetes (53.4%). Resistance to clindamycin increased from 37.0% of isolates in 2011 to 43.2% in 2016 (P = .02). Serotypes Ia, Ib, II, III, and V accounted for 86.4% of isolates in 2016; serotype IV increased from 4.7% in 2008 to 11.3% in 2016 (P

Neonatal infections are estimated to account for a quarter of the 2·8 million annual neonatal deaths, as well as approximately 3% of all disability-adjusted life-years. Despite this burden, few data are available on incidence, aetiology, and outcomes, particularly regarding impairment. We aimed to develop guidelines for improved scientific reporting of observational neonatal infection studies, to increase comparability and to strengthen research in this area. This checklist, Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE- NI), is an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. STROBE-NI was developed following systematic reviews of published literature (1996-2015), compilation of more than 130 potential reporting recommendations, and circulation of a survey to relevant professionals worldwide, eliciting responses from 147 professionals from 37 countries. An international consensus meeting of 18 participants (with expertise in infectious diseases, neonatology, microbiology, epidemiology, and statistics) identified priority recommendations for reporting, additional to the STROBE statement. Implementation of these STROBE-NI recommendations, and linked checklist, aims to improve scientific reporting of neonatal infection studies, increasing data utility and allowing meta-analyses and pathogen-specific burden estimates to inform global policy and new interventions, including maternal vaccines.

Background The number of reported cases of Legionnaires’ disease, a severe pneumonia caused by the bacterium Legionella, is increasing in the United States. During 2000–2014, the rate of reported legionellosis cases increased from 0.42 to 1.62 per 100 000 persons; 4% of reported cases were outbreak-associated. Legionella is transmitted through aerosolization of contaminated water. A new industry standard for prevention of Legionella growth and transmission in water systems in buildings was published in 2015. CDC investigated outbreaks of Legionnaires’ disease to identify gaps in building water system maintenance and guide prevention efforts. Methods Information from summaries of CDC Legionnaires’ disease outbreak investigations during 2000–2014 was systematically abstracted, and water system maintenance deficiencies from land-based investigations were categorized as process failures, human errors, equipment failures, or unmanaged external changes. Results During 2000–2014, CDC participated in 38 field investigations of Legionnaires’ disease. Among 27 land-based outbreaks, the median number of cases was 10 (range = 3–82) and median outbreak case fatality rate was 7% (range = 0–80%). Sufficient information to evaluate maintenance deficiencies was available for 23 (85%) investigations. Of these, all had at least one deficiency; 11 (48%) had deficiencies in ≥2 categories. Fifteen cases (65%) were linked to process failures, 12 (52%) to human errors, eight (35%) to equipment failures, and eight (35%) to unmanaged external changes. Conclusions and Implications for Public Health Practice Multiple common preventable maintenance deficiencies were identified in association with disease outbreaks, highlighting the importance of comprehensive water management programs for water systems in buildings. Properly implemented programs, as described in the new industry standard, could reduce Legionella growth and transmission, preventing Legionnaires’ disease outbreaks and reducing disease.