A prospective case-control study on the association of Rhinovirus nasopharyngeal viral load and viremia in South African children hospitalized with severe pneumonia

Abstract

Rhinovirus (RV) role in pathogenesis of severe childhood disease remains controversial. We aimed to explore the association between RV molecular subtyping, nasopharyngeal viral loads and viremia with childhood pneumonia. Nasopharyngeal and blood samples from cases and controls were tested for RV and the 5' non-coding region sequenced. The cases compared to controls had a similar prevalence of RV detection in the nasopharynx (23 % vs. 22 %, P = 0.66), similar RV species distribution (A, B, C = 44 %, 8%, 44 % vs. 48 %, 7%, 38 %; respectively; P = 0.66) and similar viral load (4.0 and 3.7 log10 copies/mL, P = 0.062). However, RV-viremia was 4.01-fold (aOR 95 % CI: 1.26-12.78) more prevalent among cases (7%) than controls (2%), P = 0.019. Furthermore, among cases and controls RV-C was more commonly associated with viremia (14 % and 4%, P = 0.023), than RV-A (2% and 1%; P = 0.529). Thus RV-viremia could be used as a measure for attributing causality to RV in children hospitalized for pneumonia.

Keywords: Children; Molecular epidemiology; Pneumonia; Rhinovirus; Viral load; Viremia.

Fig. 1

A phylogenetic analysis of RV sequences. Sequences with closed circles denote types identified in NP/OP case samples (●) and sequences with open circles denote types identified in NP/OP control samples (O). Red, closed circles () denote types identified in viremia cases and red, open circles () denoted types identified in control with viremia. Closed triangles () denote reference strains from GenBank. RV-A types are indicated by purple branches, RV-B types are indicated by green branches and RV-C are indicated by light blue branches. Bootstrap values after 1000 replicates are shown next to the branches, values <70 % have been omitted from the tree. The phylogenetic tree is drawn to scale and the branch lengths are in relation to the lengths of those used to infer the tree (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).

Fig. 2

Reverse cumulative plots of NP/OP RV load in Panel A.) all RV-infected viremic (n = 17) and non-viremic participants (n = 370), Panel B.) cases positive for viremia (n = 13) vs. non-viremic cases (n = 185), Panel C.) community controls positive for viremia (n = 4) vs. non-viremic controls (n = 185), Panel D.) all RV-C viremic (n = 14) and non-viremic participants (n = 156), Panel E.) RV-C viremic cases (n = 11) compared to RV-C non-viremic cases (n = 80), Panel F.) RV-C viremic (n = 3) community controls compared to RV-C associated non-viremic controls (n = 76).