Jennifer R. Verani

Effectiveness of ten-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in Brazil: a matched case-control study

BACKGROUND In March 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10), which was licensed based on non-inferiority of immunological correlates of protection compared with the seven-valent vaccine. The schedule comprised three primary doses at ages 2 months, 4 months, and 6 months, and a booster dose at age 12 months. A single catch-up dose was offered for children aged 12-23 months at the time of introduction. We assessed PCV10 effectiveness against invasive pneumococcal disease in Brazilian children. METHODS Invasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid, or another normally sterile site, was identified in children age-eligible for at least one PCV10 dose through laboratory-based and hospital-based surveillance in ten states in Brazil from March 1, 2010, until Dec 31, 2012. We aimed to identify four age-matched and neighbourhood-matched controls for each case. We used conditional logistic regression and calculated PCV10 effectiveness as (1-adjusted matched odds ratio) × 100% for vaccine-type and vaccine-related serotypes (ie, in the same serogroup as a vaccine serotype). FINDINGS In 316 cases (median age 13·2 months, range 2·6-53·1) and 1219 controls (13·3 months, 2·6-53·1), the adjusted effectiveness of an age-appropriate PCV10 schedule was 83·8% (95% CI 65·9-92·3) against vaccine serotypes, and 77·9% (41·0-91·7) against vaccine-related serotypes. Serotype-specific effectiveness was shown for the two most common vaccine serotypes-14 (87·7%, 60·8-96·1) and 6B (82·8%, 23·8-96·1)-and serotype 19A (82·2%, 10·7-96·4), a serotype related to vaccine serotype 19F. A single catch-up dose in children aged 12-23 months was effective against vaccine-type disease (68·0%, 17·6-87·6). No significant effectiveness was shown against non-vaccine serotypes for age-appropriate or catch-up schedules. INTERPRETATION In the routine immunisation programme in Brazil, PCV10 prevents invasive disease caused by vaccine serotypes. PCV10 might provide cross-protection against some vaccine-related serotypes. FUNDING Brazilian Ministry of Health, Pan-American Health Organization, and US Centers for Disease Control and Prevention.

Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: Experience in the United States and implications for a potential group B streptococcal vaccine

Group B Streptococcus (GBS) emerged as the leading cause of newborn infection in the United States in the 1970s. In the 1980s clinical trials demonstrated that giving intrapartum intravenous ampicillin or penicillin to mothers at risk was highly effective at preventing invasive GBS disease in the first week of life (early-onset). In 1996, the first national guidelines for the prevention of perinatal GBS disease were issued; these recommended either antenatal screening for GBS colonization and intrapartum antimicrobial prophylaxis (IAP) to colonized women, or targeting IAP to women with certain obstetric risk factors during labor. In 2002, revised guidelines recommended universal antenatal GBS screening. A multistate population-based review of labor and delivery records in 2003-2004 found 85% of women had documented antenatal GBS screening; 98% of screened women had a colonization result available at labor. However, missed opportunities for prevention were identified among women delivering preterm and among those with penicillin allergy, and more false negative GBS screening results were observed than expected. The incidence of invasive early-onset GBS disease decreased by more than 80% from 1.8 cases/1000 live births in the early 1990s to 0.26 cases/1000 live births in 2010; from 1994 to 2010 we estimate that over 70,000 cases of EOGBS invasive disease were prevented in the United States. IAP effectiveness is similar and high among term (91%) and preterm (86%) infants when first line therapy is received for at least 4h. However, early-onset disease incidence among preterm infants remains twice that of term infants; moreover disease among infants after the first week of life (late-onset disease) has not been impacted by IAP. The US experience demonstrates that universal screening and IAP for GBS-colonized women comprise a highly effective strategy against early-onset GBS infections. Maximizing adherence to recommended practices holds promise to further reduce the burden of early-onset GBS disease. Yet there are also inherent limitations to universal screening and IAP. Some of these could potentially be addressed by an efficacious maternal GBS vaccine.

Group B streptococcal disease in infants: Progress in prevention and continued challenges

The burden of early-onset disease caused by group B Streptococcus (GBS) has decreased dramatically in the United States over the past 20 years. Universal culture-based screening at 35 to 37 weeks gestational age and use of intrapartum antibiotic prophylaxis are the cornerstones of prevention measures that have led to this decline. GBS, however, remains the leading cause of early-onset neonatal sepsis in the United States. Revised guidelines for prevention of perinatal GBS are planned for issuance in 2010. This article discusses implementation challenges for clinicians caring for pregnant women and newborns and presents an updated algorithm for neonatal management.

Cost-effectiveness of a potential group B streptococcal vaccine program for pregnant women in South Africa

BACKGROUND In low- and middle-income countries neonatal infections are important causes of infant mortality. Group B streptococcus (GBS) is a major pathogen. A GBS polysaccharide-protein conjugate vaccine, the only option that has the potential to prevent both early- and late-onset GBS disease, has completed Phase II trials. Screening-based intrapartum antibiotic prophylaxis (IAP) for pregnant women, an effective strategy in high-income countries, is often not practical in these settings. Risk factor-based IAP (RFB-IAP) for women with risk factors at delivery has had limited success in preventing neonatal infection. We evaluated the cost and health impacts of maternal GBS vaccination in South Africa. METHODS AND FINDINGS We developed a decision-analytic model for an annual cohort of pregnant women that simulates the natural history of GBS disease in their infants. We compared four strategies: doing nothing, maternal GBS vaccination, RFB-IAP, and vaccination plus RFB-IAP. Assuming vaccine efficacy varies from 50% to 90% against covered serotypes and 75% of pregnant women are vaccinated, GBS vaccination alone prevents 30-54% of infant GBS cases compared to doing nothing. For vaccine prices between

Indirect cohort analysis of 10-valent pneumococcal conjugate vaccine effectiveness against vaccine-type and vaccine-related invasive pneumococcal disease.

10 and

Impact of vaccination against Haemophilus influenzae type b with and without a booster dose on meningitis in four South American countries

30, and mid-range efficacy, its cost ranges from

Cost-effectiveness of a potential group B streptococcal vaccine for pregnant women in the United States

676 to

Case-control vaccine effectiveness studies: Preparation, design, and enrollment of cases and controls

2390 per disability-adjusted life-year (DALY) averted (

Incidence of Hospitalized Pneumococcal Pneumonia among Adults in Guatemala, 2008-2012

US 2010), compared to doing nothing. RFB-IAP alone, compared to doing nothing, prevents 10% of infant GBS cases at a cost of

Case-control vaccine effectiveness studies: Data collection, analysis and reporting results

240/DALY. Vaccine plus RFB-IAP prevents 48% of cases at a cost of