Elsevier

Vaccine

Volume 32, Issue 17, 7 April 2014, Pages 1954-1963
Vaccine

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

https://doi.org/10.1016/j.vaccine.2014.01.062Get rights and content

Highlights

  • A maternal group B streptococcal (GBS) vaccine is currently in trials.

  • Maternal GBS vaccination would reduce the GBS disease burden in South Africa and be very cost-effective by WHO guidelines.

  • Risk factor-based intrapartum antibiotic prophylaxis (RFB-IAP) is also very cost-effective but has limited health impact.

  • Vaccination plus RFB-IAP would be more effective and more costly than vaccination alone, but still very cost-effective.

  • Vaccine will be an especially useful public health tool in settings where RFB-IAP is not feasible.

Abstract

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 $10 and $30, and mid-range efficacy, its cost ranges from $676 to $2390 per disability-adjusted life-year (DALY) averted ($US 2010), compared to doing nothing. RFB-IAP alone, compared to doing nothing, prevents 10% of infant GBS cases at a cost of $240/DALY. Vaccine plus RFB-IAP prevents 48% of cases at a cost of $664–2128/DALY.

Conclusions

Vaccination would substantially reduce the burden of infant GBS disease in South Africa and would be very cost-effective by WHO guidelines. RFB-IAP is also very cost-effective, but prevents only 10% of cases. Vaccination plus RFB-IAP is more effective and more costly than vaccination alone, and consistently very cost-effective.

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)

  • A. Sinha et al.

    The projected health benefits of maternal group B streptococcal vaccination in the era of chemoprophylaxis

    Vaccine

    (2005)
  • R.L. Goldenberg et al.

    Epidemiology and causes of preterm birth

    Lancet

    (2008)
  • J.A. Salomon et al.

    Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010

    Lancet

    (2012)
  • S.A. Madhi et al.

    High burden of invasive Streptococcus agalactiae disease in South African infants

    Ann Trop Paediatr

    (2003)
  • H.N. Bomela et al.

    Is prophylaxis of early-onset group B streptococcal disease appropriate for South Africa

    S Afr Med J

    (2001)
  • C.L. Cutland et al.

    Maternal HIV infection and vertical transmission of pathogenic bacteria

    Pediatrics

    (2012)
  • F.Y. Lin et al.

    Level of maternal antibody required to protect neonates against early-onset disease caused by group B Streptococcus type Ia: a multicenter, seroepidemiology study

    J Infect Dis

    (2001)
  • F.Y. Lin et al.

    Level of maternal IgG anti-group B streptococcus type III antibody correlated with protection of neonates against early-onset disease caused by this pathogen

    J Infect Dis

    (2004)
  • C.J. Baker et al.

    Group B streptococcal conjugate vaccines

    Arch Dis Child

    (2003)
  • P.T. Heath

    An update on vaccination against group B streptococcus

    Expert Rev Vaccines

    (2011)
  • National Library of Medicine (US). ClinicalTrials.gov. http://www.clinicaltrials.gov www.clinicaltrials.gov (accessed...
  • Cited by (0)

    View full text