Temporal association of rotavirus vaccination and genotype circulation in South Africa: Observations from 2002 to 2014
Introduction
Globally, rotavirus mortality in children <5 years was estimated at 527,000 (465,000–591,000) in 2000 and reduced to 215,000 (197,000–233,000) in 2013 with more than half of the latter occurring in sub-Saharan Africa [1]. Two rotavirus vaccines (Rotarix, GlaxoSmithKline Biologicals and RotaTeq, Merck & Co) have been shown to be both safe and effective [2]. The delivery of rotavirus vaccines to children in sub-Saharan Africa should, therefore, provide an important tool in the fight against diarrhoeal diseases [3].
The icosahedral rotavirus particle has outer capsid proteins, VP7 and VP4, that are able to independently elicit an immune response and were important epitopes during vaccine development [4]. These proteins specify the G and P genotypes, respectively, and to date 35 G and 50 P genotypes have been described [5], [6]. In human infections, five globally predominant (G1, G2, G3, G4 and G9), one recently emerged (G12) and one regionally predominant (G8) G types circulate while two globally predominant (P[8] and P[4]) and one regionally predominant (P[6]) P genotypes are detected [7], [8].
In South Africa (SA) between 2003 and 2005, a prospective burden of disease study investigated children <5 years presenting to the Dr George Mukhari Hospital (DGM) for the treatment of diarrhoea. The study estimated that rotavirus was responsible for 17,644–25,630 hospitalizations in children <2 years of age annually [9]. The study also examined rotavirus genotypes prior to vaccine introduction [10]. The dominant rotavirus genotype varied year on year (G2P[4] in 2003, G1P[8]/G1P[6] in 2004, G3P[8]/G3P[6] in 2005 and G1P[8] in 2006) and a variety of unusual genotypes and G/P combinations were detected [10].
In August 2009, the rotavirus vaccine was introduced into the South African public immunization Program. Preliminary impact analysis estimated that rotavirus vaccine introduction reduced rotavirus hospitalizations by 54–58% in 2010 and 2011 in children <5 years [11]. Further, a case control study from SA demonstrated rotavirus vaccine effectiveness against rotavirus diarrhoea hospitalization of 57% (95% CI 40–68) for two doses [12].
After the introduction of the monovalent rotavirus vaccine in Mexico and Brazil, reports of increases in the proportion of rotavirus genotypes not present in the vaccine formulation emerged raising concern around replacement disease due to non-vaccine genotypes [13], [14]. In Malawi, post-monovalent vaccine introduction surveillance found higher vaccine effectiveness against fully or partially homotypic rotavirus strains, with lower estimates for heterotypic strains [15]. In Botswana, G2P[4] predominated after monovalent vaccine introduction with G2P[4] vaccine effectiveness of 59% [16]. However, subsequent analyses showed similar vaccine effectiveness against homotypic and heterotypic strains and, lack of dominance of any one rotavirus strain post-vaccine introduction [17].
Nevertheless, recent modelling utilizing genotype-specific hospitalization data from Belgium pre- and post-vaccine introduction, predicted that G1P[8] strains would be eliminated while G2P[4] strains would persist, which was suggested to be driven by differences in homotypic versus heterotypic immunity of second infections [18]. To date, there is limited characterisation of rotavirus genotypes post-vaccine introduction from African countries and continued surveillance is required to elucidate what effect (if any) rotavirus vaccination has on circulating rotavirus strains in resource poor settings.
The aim of this study was to evaluate the rotavirus genotype distribution before (2002–2009) and after (2010–2014) rotavirus vaccine introduction into the South African national immunization program.
Section snippets
Materials and methods
Hospital-based rotavirus surveillance in children <5 years presenting with acute diarrhoea has been conducted at DGM since early 1980s [19]. Data on rotavirus detection and genotype distribution from DGM between 2002 and 2008 were obtained from the Medical Research Council of South Africa-Diarrhoeal Pathogens Research Unit (MRC-DPRU) based at Sefako Makgatho Health Sciences University. A dedicated surveillance officer approached parents/guardians of children <5 years admitted for the treatment
Temporal changes in rotavirus prevalence and genotype distribution pre- and post-vaccine introduction at Dr George Mukhari Hospital
Between January 2002 and December 2014, 6870 stool specimens from DGM were screened with 23% (95% confidence interval (95% CI) 20–25; 1588/6870) positive for rotavirus (Table 1). The annual detection rate ranged from 17% (95% CI 15–20) in 2003 and 2012 (95% CI 12–24) to 30% in 2006 (95% CI 27–37; Table 1) and the proportion of rotavirus positive specimens did not change significantly over the time period (p for trend = .08).
Among rotavirus positive specimens, the proportion of G1 strains varied
Discussion
The current study suggests that the monovalent rotavirus vaccine introduction into the national immunization program was temporally associated with changes in genotype circulation in SA. The decrease in G1 strains was similar at DGM, a site with genotyping data from 2002, as well as geographically diverse sentinel sites, using 2009 as a baseline. In Malawi, G1P[8] prevalence showed a non-significant decline of 54% post-vaccine introduction compared to the pre-vaccine era [15]. In Morocco,
Ethical standards
Ethical approval for the study was obtained from the Human Research Ethics Committee (Medical), University of Witwatersrand (M091018), the Biomedical Research Ethics Committee, University of Kwa-Zulu Natal (BF074/09), the Medunsa Research Ethics Committee, University of Limpopo (MREC/P/10/2009) and the Human Research Ethics Committee, University of Cape Town (068/2010).
Financial support
The expanded diarrhoea sentinel surveillance program was funded by GlaxoSmithKline (E-Track 200238). The funders were not involved in study design, writing or publication of the paper.
Declaration of interests
NAP received personal fees from GlaxoSmithKline, Merck and Aspen Pharma.
MJG received personal fees from GlaxoSmithKline and funding from PATH Vaccine Solutions.
CC received personal fees from Sanofi Pasteur and Pfizer.
SAM received personal fees from Pfizer and funding from PATH, Novartis and GlaxoSmithKline.
Acknowledgements
Site surveillance officers and managers for data and specimen collection, CED laboratory staff for routine molecular surveillance (Tersia Kruger, Sandrama Nadan, Rembuluwani Netshikweta); MRC-DPRU laboratory staff for routine molecular surveillance (Ina Peenze, Kebareng Rakau).
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