Cost-effectiveness of a potential group B streptococcal vaccine program for pregnant women in South Africa
Introduction
Group B streptococcal (GBS) infection is a major cause of neonatal mortality and morbidity in low- and middle-income countries, particularly in sub-Saharan Africa [1]. A recent meta-analysis reported GBS disease incidence in African infants aged 0–89 days at 1.21 per 1000 live births, with case fatality 22% [2]. In South Africa, an upper middle-income country, early-onset GBS disease (EOGBS, sepsis or meningitis caused by GBS in the first week of life) and late-onset disease (LOGBS, onset at 7–90 days of age) are associated with significant disease burden [3], [4], with approximately one third of the burden attributable to LOGBS [3]. Incidence of EOGBS plus LOGBS in a recent clinical trial there was 3 per 1000 live births [5], [6].
Sero-epidemiological studies have established a strong association between acquisition of maternal anti-capsular antibodies in utero and newborns’ risk of developing invasive GBS disease [7], [8]. Serotype-specific polysaccharide–protein conjugate GBS vaccines currently under evaluation would increase the concentration of anti-capsular antibodies transferred trans-placentally to newborns, preventing invasive GBS disease for those serotypes [9]. Since the 1980s, several candidate vaccines have been studied [10], but none is yet available for use in humans [11]. A trivalent (serotypes Ia, Ib, and III) conjugate GBS vaccine that may prevent both EOGBS and LOGBS has completed Phase II clinical trials in pregnant women in South Africa and other countries (no results were available as of December 2013) [12].
In countries like the U.S., antenatal screening for maternal GBS colonization, followed by intrapartum antibiotic prophylaxis (IAP), has significantly reduced EOGBS burden [11], [13], [14]. In South Africa, antenatal screening for GBS colonization, which requires sampling and culture, is not widely implemented [5]. Instead a risk factor-based approach (RFB-IAP) – antibiotics during labor for women with risk factors for EOGBS such as chorioamnionitis, prolonged rupture of membrane (PROM), or preterm delivery – is part of recommended obstetrical guidelines [4], [15]. Even when optimally implemented, RFB-IAP does not prevent LOGBS.
Given the difficulties of expanding IAP in middle- and low-income countries, experts convened by the Centers for Disease Control and Prevention in 2010 concluded that maternal vaccination to prevent GBS disease in newborns had “untapped potential” to reduce the toll from the disease [16]. They recommended that the investment case for maternal vaccination be explored now so that the information would be available even before Phase III trials, currently being planned, begin. In response to this recommendation, we evaluated the potential health and economic impacts of maternal GBS vaccination in South Africa, a country relatively rich in data, using a decision-analytic model, in order to provide policy makers with early insights into the value of vaccine development and introduction. We compared a potential GBS vaccine with the conventional comparator for vaccination, doing nothing, with RFB-IAP, and with a combination strategy using both RFB-IAP and vaccine.
Section snippets
Methods
The model is structured as a decision tree that describes the interventions offered to pregnant women, with embedded Markov nodes to model the consequences over the lifetimes of their babies, using TreeAge Pro 2012 (TreeAge Inc., Williamstown, MA) (Appendix A1). In the model, pregnant women are subdivided into 16 risk groups by birth order (first/subsequent pregnancy), gestational age (preterm delivery [<37 weeks] vs. term [≥37 weeks]), and risk factors at delivery (chorioamnionitis/maternal
Health outcomes (Fig. 1, Panels A and B)
In the absence of RFB-IAP or vaccination, the 2010 South African cohort of 1,294,694 live births would experience 9801 cases of invasive GBS disease, 1758 GBS deaths, 54,910 GBS-related DALYs, and 7,674,722 overall DALYs.
Assuming 75% vaccination coverage, as vaccine efficacy against covered serotypes is varied from 50% to 90%, maternal vaccination would prevent 2912–5260 cases of GBS disease (1912–3462 EOGBS, 1000–1798 LOGBS; 30–54% reduction), compared with doing nothing, 516–934 GBS deaths
Discussion
Neonatal sepsis, in which GBS disease plays a prominent role, imposes a significant disease burden in low- and middle-income countries, causing 26% of deaths in infants aged less than 90 days [29]. Preventing these deaths is a public health priority as countries endeavor to reach Millennium Development Goals to reduce under-five deaths by two-thirds by 2015 [30].
If trials demonstrate effectiveness, maternal GBS vaccination would save lives and reduce the burden of GBS disease in South African
Acknowledgements
The authors are grateful to the following for their input as expert panelists: Debbie Atherly, Carol Baker, Logan Brenzel, Dagna Constenla, Ulla Griffiths, Paul Heath, Keith Klugman, Carol Levin, and Anne Schuchat.
Financial disclosure: This study was supported by grants from the U.S. Centers for Disease Control and Prevention (Atlanta, GA, USA) and PATH (Seattle, WA, USA). Two (Jennifer R. Verani and Stephanie J. Schrag) of the coauthors are employees of the U.S. CDC, and one (Debbie Atherly)
References (43)
- et al.
An overview of global GBS epidemiology
Vaccine
(2013) - et al.
Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis
Lancet
(2012) - et al.
Chlorhexidine maternal–vaginal and neonate body wipes in sepsis and vertical transmission of pathogenic bacteria in South Africa: a randomised, controlled trial
Lancet
(2009) - et al.
A maternal vaccine against group B Streptococcus: past, present, and future
Vaccine
(2013) - et al.
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
Vaccine
(2013) Group B streptococcal vaccine for resource-poor countries
Lancet
(2011)- et al.
The effectiveness of risk-based intrapartum chemoprophylaxis for the prevention of early-onset neonatal group B streptococcal disease
Am J Obstet Gynecol
(2001) Group B streptococcus
Lancet
(1999)- et al.
WHO estimates of the causes of death in children
Lancet
(2005) - et al.
Progress towards Millennium Development Goals 4 and 5 on maternal and child mortality: an updated systematic analysis
Lancet
(2011)