Rotavirus Genotypes in Hospitalized Children With Acute Gastroenteritis Before and After Rotavirus Vaccine Introduction in Blantyre, Malawi, 1997–2019

Abstract

Introduction Rotavirus vaccine (Rotarix®, RV1) has reduced diarrhea-associated hospitalizations and deaths in Malawi. We examined the trends in circulating rotavirus genotypes in Malawi over a 22-year period to assess the impact of RV1 introduction on strain distribution. Methods Data on rotavirus-positive stool specimens among children age <5 years hospitalized with diarrhea in Blantyre, Malawi before (July 1997 – October 2012, n=1765) and after (November 2012 – October 2019, n=934) RV1 introduction were analyzed. Rotavirus G and P genotypes were assigned using reverse transcription polymerase chain reaction. Results A rich rotavirus strain diversity circulated throughout the 22-year period; Shannon (H) and Simpson diversity (D) indices did not differ between the pre- and post-vaccine periods (H’ p < 0.149: D’ p < 0.287). Overall, G1 (n=268/924; 28.7%), G2 (n=308/924; 33.0%), G3 (n=72/924; 7.7%) and G12 (n=109/924; 11.8%) were the most prevalent genotypes identified following RV1 introduction. The prevalence of G1P[8] and G2P[4] genotypes declined each successive year following RV1 introduction, and were not detected after 2018. Genotype G3 re-emerged and became the predominant genotype from 2017. No evidence of genotype selection was observed seven years post-RV1 introduction. Conclusion Rotavirus strain diversity and genotype variation in Malawi is likely driven by natural mechanisms rather than vaccine pressure.

Multiple Introductions and Predominance of Rotavirus Group A Genotype G3P[8] in Kilifi, Coastal Kenya, 4 Years after Nationwide Vaccine Introduction

“…Several recent studies have reported the increased proportion of G3P [8] strains, e.g., in Australia [14], Japan [32], Thailand [28], Indonesia [29], Pakistan [33], Dominican Republic [25], Brazil [34], Spain [20], Mozambique [24], Malawi [35] and Botswana [36]. The global G3 sequences available from GenBank showed extensive genetic diversity.…”

“…Continued surveillance to monitor whether this particular strain becomes endemic in Kenya and the wider Africa continent in the face of increased RVA vaccine coverage is important to optimize RVA vaccine-mediated control. Notably, recent studies in Botswana [36], Mozambique [24], Malawi [35] and Ethiopia [37] reported increased prevalence of G3 type viruses but sequencing data from these studies are not yet available.…”

Reduction in severity of all-cause gastroenteritis requiring hospitalisation in children vaccinated against rotavirus in Malawi

“…The dsRNA was reverse transcribed to complementary DNA (cDNA) using random primers (Invitrogen, Paisley, UK) and reverse transcriptase enzyme (Superscript III MMLV-RT, Invitrogen, Paisley, UK) [9]. The cDNA was used to assign G genotype (G1, G2, G3, G4, G8, G9, G10, G11, G12) and P genotype (P [4], P [6], P [8], P [9], P [10], P [11], P [14]) using a multiplex heminested RT-PCR as described previously [5].…”

“…The most frequently detected rotavirus genotypes were G1P [8], G2P [4], G2P [6], G12P [6] and G12P [8] [5], which comprised 66.57% (636/1,050) of all genotypes (Table S3). In RV1 unvaccinated children, regardless of the genotype, most gastroenteritis episodes were classified as severe (66.67%, 424/636) and severity scores did not differ by genotype (unadjusted Kruskal-Wallis test, P=0.544).…”

“…At least 36 G types and 51 P types have been reported (https://rega.kuleuven.be/cev/viralmetagenomics/virusclassification). Of these, genotypes G1P [8], G2P [4], G3P [8], G4P [8], G9P [8] and G12P [8] are the most frequent cause of rotavirus disease in humans worldwide [4,5].…”