Epidemiology and genotypes of Enteroviruses in patients with respiratory illness in South Africa
Date
2020
Authors
Hellferscee, Orienka
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Abstract
Globally, lower respiratory tract infections (LRTI) are the leading cause of death
in children aged less than 5 years. This study focuses on enteroviruses, which are
a known cause of respiratory illness but whose epidemiology and molecular
characterization have not been well described in South Africa.
The first aim of this study was to describe enterovirus genotypes circulating
among South African patients hospitalized with severe respiratory illness (SRI).
Upper respiratory samples were tested for the presence of enteroviruses using
polymerase chain reaction (PCR) and characterized using a partial VP1 gene
segment through Sanger sequencing. Enteroviruses were identified in 8.2% of
patients with SRI. We demonstrated a high diversity, 17 genotypes, from all four
enterovirus species circulating in South Africa.
The second aim was to use Sanger sequencing to characterize the enterovirus
genotypes circulating among South African patients with influenza-like illness
(ILI), SRI, and asymptomatic individuals. We found high genetic diversity (33
genotypes) but no association of enterovirus species with disease severity;
however, some genotypes (echovirus 30 (E30), coxsackie virus B5, and EV-D68)
were more prevalent in symptomatic cases. The E30 strains formed a new cluster
proposed to be named genotype k.
The third aim described a novel approach for next generation sequencing of E30,
based on sequence-independent single primer amplification (SISPA). Complete
full genome phylogenetic analysis supports the designation of genotype k, and
distinct grouping was confirmed that could be a result of the diversity of different
subgenomic regions in E30 driven by different evolutionary paths. Five E30
whole genomes were submitted to GenBank, contributing to global data.
The fourth aim was to determine the fraction of rhinovirus (the most commonly
identified species of Enterovirus) detection associated with mild or severe
respiratory illness. Rhinovirus was detected in 17.4% (368/2120), 26.8%
(979/3654) and 23.0% (1003/4360) of controls, ILI and SRI, respectively. The overall RV-AF (ILI: 54.6%; severe acute respiratory illness (SARI): 54.3%) were
similar to those reported in a previous study conducted in South Africa (ILI:
52.0%; SARI: 46.9%), but was lower compared to those of other important
respiratory pathogens such as influenza viruses (ILI: 93.3%; SARI: 86.3%) and
respiratory syncytial virus (ILI: 63.1%; SARI: 83.7%) (21). Even though the
attributable fraction was lower than influenza and RSV, the attributable burden of
rhinoviruses (RV-AF) was equivalent to influenza and RSV, because of the high
rhinovirus detection rate.
In conclusion, we found (i) no difference in enterovirus genotypes detected in
mild versus severe disease; (ii) that outbreak-associated EV strains like EV-D68
are circulating in South Africa; (iii) that E30 strains from respiratory illness cases
in South Africa belong to a newly proposed genotype k; and (iv) that rhinovirus
species contribute to mild and severe respiratory illness
Description
A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirement for the degree of Doctor of Philosophy