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Increased Risk for Group B Streptococcus Sepsis in Young Infants Exposed to HIV, Soweto, South Africa, 2004–20081 - Volume 21, Number 4—April 2015 - Emerging Infectious Disease journal - CDC


Increased Risk for Group B Streptococcus Sepsis in Young Infants Exposed to HIV, Soweto, South Africa, 2004–20081 - Volume 21, Number 4—April 2015 - Emerging Infectious Disease journal - CDC

Volume 21, Number 4—April 2015


Increased Risk for Group B Streptococcus Sepsis in Young Infants Exposed to HIV, Soweto, South Africa, 2004–20081

Clare L. CutlandComments to Author , Stephanie J. Schrag, Michael C. Thigpen, Sithembiso C. Velaphi, Jeannette Wadula, Peter V. Adrian, Locadiah Kuwanda, Michelle J. Groome, Eckhart Buchmann, and Shabir A. Madhi
Author affiliations: University of the Witwatersrand, Johannesburg, South Africa (C.L. Cutland, S.C. Velaphi, J. Wadula, P.V. Adrian, L. Kuwanda, M.J. Groome, E. Buchmann, S.A. Madhi)Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Johannesburg (C.L. Cutland, P.V. Adrian, L. Kuwanda, M.J. Groome, S.A. Madhi)Centers for Disease Control and Prevention, Atlanta, Georgia, USA (S.J. Schrag, M.C. Thigpen)Chris Hani Baragwanath Academic Hospital, Johannesburg (S.C. Velaphi, J. Wadula, E. Buchmann)National Institute for Communicable Diseases, Sandringham, South Africa (S.A. Madhi)


Although group B Streptococcus (GBS) is a leading cause of severe invasive disease in young infants worldwide, epidemiologic data and knowledge about risk factors for the disease are lacking from low- to middle-income countries. To determine the epidemiology of invasive GBS disease among young infants in a setting with high maternal HIV infection, we conducted hospital-based surveillance during 2004–2008 in Soweto, South Africa. Overall GBS incidence was 2.72 cases/1,000 live births (1.50 and 1.22, respectively, among infants with early-onset disease [EOD] and late-onset [LOD] disease). Risk for EOD and LOD was higher for HIV-exposed than HIV-unexposed infants. GBS serotypes Ia and III accounted for 84.0% of cases, and 16.9% of infected infants died. We estimate that use of trivalent GBS vaccine (serotypes Ia, Ib, and III) could prevent 2,105 invasive GBS cases and 278 deaths annually among infants in South Africa; therefore, vaccination of all pregnant women in this country should be explored.
In 2013, a total of 41.6% (2.6 million) of deaths worldwide in children <5 years of age occurred in neonates; 76.7% occurred within 6 days after birth (1). Furthermore, in 2012, ≈6.9 million probable cases of severe bacterial infections and 680,000 associated deaths occurred among neonates (2). Nevertheless, there is a paucity of data from low- and middle-income countries on pathogen-specific causes of neonatal sepsis, particularly during the first day of life, and it is unknown whether in utero HIV exposure increases susceptibility to severe neonatal bacterial infections.
Group B Streptococcus (GBS) is a leading cause of severe invasive disease in young infants. A meta-analysis dominated by studies from high-income countries estimated global incidence of 0.53 cases/1,000 live births during 2000–2011 (3). Considerable intra- and interregional variation in the incidence of invasive early-onset disease (EOD; disease in 0- to 6-day-old infants ) was observed (35), ranging from 1.21 cases/1,000 live births (95% CI 0.5–1.91) in Africa to 0.02 cases/1,000 live births (95% CI 0–0.07) in Southeast Asia (3). This variability is inconsistent with the lesser difference in prevalence of maternal GBS colonization, the major risk factor for EOD, in women from different regions (20.9% in Africa, 13.4% in Southeast Asia) (6). Maternal HIV infection has not been associated with a higher prevalence of GBS colonization (7,8), except among women with CD4+ lymphocyte counts of >500 cells/mm3 (8).
Providing intrapartum antimicrobial drug prophylaxis (IAP) to women identified as rectovaginally colonized by GBS at 35–37 weeks’ of pregnancy has been associated with a >80.0% reduction in EOD (9); however, this strategy is logistically challenging to implement and maintain in resource-constrained settings. Furthermore, IAP has not decreased the incidence of late-onset disease (LOD; disease in 7- to 90-day-old infants) (10).
Progress has been made in the development of a trivalent GBS polysaccharide–protein conjugate vaccine (GBS-CV), which is targeted for use in pregnant women; the goal is to enhance transplacental transfer of capsular antibody to the fetus (1,810), which could protect against EOD and LOD. Improved estimates of the incidence of invasive GBS disease are needed from low- and middle-income countries to contextualize the prioritization of GBS vaccination and determine whether temporal changes in invasive serotypes should be considered in the design of serotype-specific GBS vaccine.
We evaluated the clinical and microbiological epidemiology, incidence, and serotype distribution of invasive GBS disease among young infants in a setting with a high prevalence of maternal HIV infection. A secondary aim was to estimate the potential effect of a trivalent GBS-CV in reducing the number of invasive GBS cases nationally.

Dr. Cutland is a senior research medical doctor in the Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, and PhD student at the University of the Witwatersrand. Her research interests include epidemiology and prevention of vaccine-preventable diseases in children, particularly young infants.


We thank the staff of Departments of Obstetrics, Neonatology, and Paediatrics at CHBAH for their dedication to their patients, including our study participants. We also thank Mannikhant Khoosal for assisting with sample collection and logistical support; Suzett Fourie, Veebha Gosai, Razia Hassan Moosa, Waasila Jassat, Stephanie Jones, Anthonet Koen, Marianne Kohler, Martin Laque and Albert Maribe for collection and analysis of data; and Mashudu Madzivhandila for sample processing.
This study was supported by the United States Agency for International Development, the National Vaccine Program Office, and the Antimicrobial Resistance Working Group of the Centers for Disease Control and Prevention (cooperative agreement nos. U50/CCU021960 and 5U01CI000318), and the Bill and Melinda Gates Foundation (grant no. 39415). Additional funding was provided by the Respiratory and Meningeal Pathogens Research Unit of the South African Medical Research Council.
The CHBAH Respiratory and Meningeal Pathogens Research Unit receives institutional grant support related to GBS from Novartis. S.A.M., C.L.C., and M.J.G. are clinical investigators in the Novartis GBS conjugate vaccine program.


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Technical Appendix

Suggested citation for this article: Cutland CL, Schrag SJ, Thigpen MC, Velaphi SC, Wadula J, Adrian PV, et al. Increased risk for group B Streptococcussepsis in young infants exposed to HIV, Soweto, South Africa, 2004–2008. Emerg Infect Dis. 2015 Apr [date cited].http://dx.doi.org/10.3201/eid2104.141562
DOI: 10.3201/eid2104.141562
1Preliminary results from this study were presented at the 8th World Congress of the World Society for Pediatric Infectious Diseases, November 19–22, 2013, Cape Town, South Africa.

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