Epidemiology of invasive bacterial infections in pneumococcal conjugate vaccine-vaccinated and -unvaccinated children under 5 years of age in Soweto, South Africa: a cohort study from a high-HIV burden setting

ABSTRACT

Background: There are limited data on paediatric invasive bacterial infections (IBI) and the impact of pneumococcal conjugate vaccine (PCV) on the spectrum of IBI pathogens, specifically in African countries with a high prevalence of HIV infection.

Aim: To describe the epidemiology of IBI in a cohort of children <5 years of age in Soweto, South Africa.

Methods: A cohort of children enrolled into a PCV9 efficacy trial conducted from 1998 until 2005 was used for secondary data analysis. Surveillance data were collected from admission wards at Chris Hani Baragwanath Academic Hospital. The incidence of IBI was calculated using person-time, stratified by age group, gender, PCV9 vaccination status and HIV infection status. Risk factors for IBI were investigated using binomial logistic regression.

Results: A total of 395 cases of laboratory-confirmed IBI were identified. HIV infection and not receiving PCV9 vaccination were risk factors for IBI hospitalisation. PCV9 vaccination was associated with reductions in IBI hospitalisation (IRR 0.76, p = 0.006) solely owing to reductions in the incidence of Streptococcus pneumoniae (IRR 0.56, p < 0.001). PCV9 vaccination had no effect on the incidence of Haemophilus influenza type b or Salmonella species IBI. There was an increase in Klebsiella species IBI (IRR 3.50, p = 0.019) and a trend towards a higher incidence of Staphylococcus aureus IBI (IRR 1.90, p = 0.099) in PCV9-vaccinated children.

Conclusions: PCV9 vaccination was effective in reducing the incidence of IBI hospitalisation in children through reductions in the incidence of S. pneumoniae. The results show that trends in other IBI causative pathogens (specifically S. aureus and Klebsiella species) should be monitored in the era of PCV vaccination.

Abbreviations: ART, antiretroviral therapy; CI, confidence interval; Hib, Haemophilus influenza type b; HIV, human immunodeficiency virus; HIV+PCV-, HIV-infected, placebo-vaccinated group; HIV+PCV+, HIV-infected, PCV9-vaccinated group; HIV-PCV-, HIV-uninfected, placebo-vaccinated group; HIV+PCV+, HIV-infected, PCV9-vaccinated group; IBI, invasive bacterial infection; IPD, invasive pneumococcal disease; IRR, incidence rate ratio; IQR, interquartile range; OR, odds ratio; PCV, pneumococcal conjugate vaccine; PCV7, 7-valent pneumococcal conjugate vaccine; PCV9, 9-valent pneumococcal conjugate vaccine; PY, person-years; RCT, randomised control trial

KEYWORDS:

• Paediatrics
• HIV
• PCV
• invasive bacterial infections
• klebsiella
• staphylococcus aureus
• streptococcus pneumoniae

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The parent PCV9 efficacy trial was funded by Wyeth. The funding sources had no involvement in the analysis.

Notes on contributors

Siobhan L. Johnstone

Siobhan L. Johnstone, associate researcher, Respiratory and Meningeal Pathogens Research Unit (RMPRU), recently completed an MSc in Epidemiology and Biostatistics at the University of the Witwatersrand. This article is part of the analysis undertaken for the project.

David P. Moore

David P. Moore , paediatric infectious diseases sub-specialist working in the public health sector in Johannesburg, South Africa, is based at the Chris Hani Baragwanath Academic Hospital, Soweto where he treats children with HIV infection, tuberculosis and other infectious diseases. His research interests include childhood pneumonia aetiology determination, prevention of infections using vaccination, childhood tuberculosis, infection prevention and control, and antibiotic stewardship. He co-supervised Ms Johnstone in her Masters of Science project.

Keith P. Klugman

Keith P. Klugman , Director, Bill and Melinda Gates Foundation Pneumonia Programme, leads the foundation’s work to reduce deaths from pneumonia, neonatal sepsis and meningitis in children, and is a co-director of the Maternal, Newborn and Child Health Discovery and Tools programme. He is an honorary professor at the RMPRU, University of the Witwatersrand, Johannesburg, South Africa. He has made major contributions in the field of pneumococcal research, including antimicrobial resistance. His work demonstrating pneumococcal conjugate vaccine efficacy in the developing world has led to interventions that have saved millions of lives, especially in Africa.

Shabir A. Madhi

Shabir A. Madhi, Professor of Vaccinology and Director of the Medical Research Council RMPRU, has been extensively involved in research on vaccine-preventable diseases and on infections in HIV-infected children. His research demonstrating a reduction in childhood morbidity with the use of pneumococcal conjugate vaccines and rotavirus vaccines prompted South Africa to be the first in Africa to introduce these vaccines in national immunisation programmes. More recently, his research has expanded to the prevention of infectious diseases during early infancy, including studies on the role of maternal immunisation in preventing sepsis in young infants.

Michelle J. Groome

Michelle J. Groome, senior researcher and medical epidemiologist at RMPRU, obtained a Master of Science in Medicine in the field of epidemiology and biostatistics in 2010 and a PhD in public health in 2016, both from the University of the Witwatersrand. She has been extensively involved in clinical research with a focus on infectious diseases, especially vaccine-preventable diseases in children. Her main area of interest includes the epidemiology and prevention of enteric (diarrhoeal) infections in children, especially rotavirus and norovirus. She co-supervised Ms Johnstone in her MSc project.