Human metapneumovirus prevalence and patterns of subgroup persistence identified through surveillance of pediatric pneumonia hospital admissions in coastal Kenya, 2007–2016

Abstract

Background Human metapneumovirus (HMPV) is an important respiratory pathogen that causes seasonal epidemics of acute respiratory illness and contributes significantly to childhood pneumonia. Current knowledge and understanding on its patterns of spread, prevalence and persistence in communities in low resource settings is limited. Methods We present findings of a molecular-epidemiological analysis of nasal samples from children < 5 years of age admitted with syndromic pneumonia between 2007 and 2016 to Kilifi County Hospital, coastal Kenya. HMPV infection was detected using real-time RT-PCR and positives sequenced in the fusion (F) and attachment (G) genes followed by phylogenetic analysis. The association between disease severity and HMPV subgroup was assessed using Fisher’s exact test. Results Over 10 years, 274/6756 (4.1%) samples screened were HMPV positive. Annual prevalence fluctuated between years ranging 1.2 to 8.7% and lowest in the recent years (2014–2016). HMPV detections were most frequent between October of one year to April of the following year. Genotyping was successful for 205/274 (74.8%) positives revealing clades A2b (41.0%) and A2c (10.7%), and subgroups B1 (23.4%) and B2 (24.9%). The dominance patterns were: clade A2b between 2007 and 11, subgroup B1 between 2012 and 14, and clade A2c in more recent epidemics. Subgroup B2 viruses were present in all the years. Temporal phylogenetic clustering within the subgroups for both local and global sequence data was seen. Subgroups occurring in each epidemic season were comprised of multiple variants. Pneumonia severity did not vary by subgroup ( p = 0.264 ). In both the F and G gene, the sequenced regions were found to be predominantly under purifying selection. Conclusion Subgroup patterns from this rural African setting temporally map with global strain distribution, suggesting a well-mixed global virus transmission pool of HMPV. Persistence in the local community is characterized by repeated introductions of HMPV variants from the global pool. The factors underlying the declining prevalence of HMPV in this population should be investigated. Electronic supplementary material The online version of this article (10.1186/s12879-019-4381-9) contains supplementary material, which is available to authorized users.

Respiratory Syncytial Virus and Human Metapneumovirus Infections in Three-Dimensional Human Airway Tissues Expose an Interesting Dichotomy in Viral Replication, Spread, and Inhibition by Neutralizing Antibodies

“…Some proteins from HMPV, including G, M2-2, and SH, are also able to inhibit the interferon response (95), but potentially to a lesser extent than RSV, which could decrease spread in comparison. Alternatively, HMPV has been shown to establish persistent infections (96)(97)(98)(99)(100)(101). Thus, it is possible that the low replication rates of HMPV in HAE tissues may drive the virus toward persistence rather than an acute infection.…”

Global Extension and Predominance of Human Metapneumovirus A2 Genotype with Partial G Gene Duplication

“…Previous studies have reported that co-circulation of several HMPV genotypes during a given season is a common occurrence [ 25 , 35 ]. An investigation carried out in Kenya concluded that a genotype predominating in one country in a given year was not necessarily the predominant genotype in other countries [ 6 ]. This indicates that a HMPV genotype could become the most prevalent in a specific area, but not necessarily represent the predominant circulating genotype in a broader region.…”

“…A study in Italy identified only one A1 genotype virus among 49 children with HMPV infection, while Kong et al identified one case among 145 HMPV infections that were genotyped in China [ 37 , 38 ]. Many recent studies have failed to detect HMPV A1 cases indicating that this genotype might have become extinct [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. The 180-nucleotide duplication in the G gene of HMPV was reported to be present in respiratory samples obtained in 2014 and onward in Japan and Spain [ 7 , 16 ].…”

“…In 2006, Huck et al first described two distinct clades of A2 viruses, termed A2a and A2b [ 4 ]. Since then, A2b viruses have been shown to cluster in two main clades which have been referred to by different names: A2b1, the clade which includes older sequences and continues to be referred to as A2b by many authors and more recently as A2.2.1; and A2b2, the clade which encompasses most recently isolated viruses, including viruses with partial duplications of the G gene, which is referred to as A2c by many authors, but also referred to as Novel A2 sublineage/Unique A2 sublineage/Unique A2b sublineage and more recently A2.2.2 [ 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. Of interest, in 2017 HMPV strains with partial duplication of the G gene were described [ 7 , 16 ].…”

Surveillance of respiratory viruses among children attending a primary school in rural coastal Kenya

“…Samples from the clinic were collected twice weekly with a maximum of 15 samples per week (details on the sample size and sampling procedures are detailed in the referenced manuscript) 22 . Children under 60 months of age admitted to the Kilifi County Hospital with syndromic severe or very severe pneumonia were enrolled as part of a continuous respiratory virus surveillance study, with NPS samples collected (details published elsewhere 28 ). Only children considered to be appropriately aged for their school grade are included in this analysis.…”