Molecular Epidemiology and Evolutionary Dynamics of Human Influenza Type-A Viruses in Africa: A Systematic Review

Abstract

Genomic characterization of circulating influenza type-A viruses (IAVs) directs the selection of appropriate vaccine formulations and early detection of potentially pandemic virus strains. However, longitudinal data on the genomic evolution and transmission of IAVs in Africa are scarce, limiting Africa’s benefits from potential influenza control strategies. We searched seven databases: African Journals Online, Embase, Global Health, Google Scholar, PubMed, Scopus, and Web of Science according to the PRISMA guidelines for studies that sequenced and/or genomically characterized Africa IAVs. Our review highlights the emergence and diversification of IAVs in Africa since 1993. Circulating strains continuously acquired new amino acid substitutions at the major antigenic and potential N-linked glycosylation sites in their hemagglutinin proteins, which dramatically affected vaccine protectiveness. Africa IAVs phylogenetically mixed with global strains forming strong temporal and geographical evolution structures. Phylogeographic analyses confirmed that viral migration into Africa from abroad, especially South Asia, Europe, and North America, and extensive local viral mixing sustained the genomic diversity, antigenic drift, and persistence of IAVs in Africa. However, the role of reassortment and zoonosis remains unknown. Interestingly, we observed substitutions and clades and persistent viral lineages unique to Africa. Therefore, Africa’s contribution to the global influenza ecology may be understated. Our results were geographically biased, with data from 63% (34/54) of African countries. Thus, there is a need to expand influenza surveillance across Africa and prioritize routine whole-genome sequencing and genomic analysis to detect new strains early for effective viral control.

Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains

“…This is the first and largest study to sequence Uganda A(H1N1)pdm09 and A(H3N2) virus whole genomes (WGs) locally, and extensively describe the genetic diversity and evolution patterns of Africa IAVs since 1994. Our work expands on previous influenza sequencing and characterisation efforts of African researchers 10 and highlights the feasibility of next-generation whole-genome sequencing for real-time disease surveillance and detection of emerging strains in Africa. Our newly-generated sequences add significantly to public Africa IAV genomes.…”

“…Based on our dataset, similar clades circulated in Uganda and other African countries, except for A(H1N1)pdm09 clade 7, HK, and H1-UG2 (Supplementary Table 7 ). However, our recent systematic review showed that clade 7-like strains also circulated in Kenya, Tanzania, and South Africa between 2010 and 2012 10 .…”

“…Here, we show evidence that a clade 3C.3a-like strain (KSY0906_A_HA-H3_Uganda_UVRI_Kisenyi_003_2011-10-19) was first sampled in 2011 and similar strains circulated in 2014 through 2017 in Uganda. While its subclade 3C.3a1 continued to circulate outside Africa through 2021, making it the longest circulating H3 subclade 10 , 37 . Strikingly, we observed A(H1N1)pdm09 strains belonging to novel subclades 6B.1A.3, 6B.1A.5a, 6B.1A.5b, and 6B.1A.6 (± T120A) sampled during 2018, 2019, 2017–2018, and 2017–2018 seasons, respectively, in Eastern, Western, and Southern Africa (Supplementary Table 7 ), but were never reported before 10 .…”

“…While its subclade 3C.3a1 continued to circulate outside Africa through 2021, making it the longest circulating H3 subclade 10 , 37 . Strikingly, we observed A(H1N1)pdm09 strains belonging to novel subclades 6B.1A.3, 6B.1A.5a, 6B.1A.5b, and 6B.1A.6 (± T120A) sampled during 2018, 2019, 2017–2018, and 2017–2018 seasons, respectively, in Eastern, Western, and Southern Africa (Supplementary Table 7 ), but were never reported before 10 . Uganda IAV strains from all geographical regions mixed, showing widespread local viral transmissions.…”

“…We systematically searched 7 databases: African Journals Online, Embase, Global Health, Google Scholar, PubMed, Scopus, and Web of Science for studies on genomic analysis of Africa IAVs. As of 30th July 2021, we found 16% (11/71) of the eligible studies sequenced and/or analyzed whole genomes (WGs) of Africa IAVs, and only 8% (5/62) of the studies that generated new viral sequences used NGS 10 . Only 3 Ugandan studies have sequenced WGs from 59 A(H3N2) 11 , 12 , and 19 A(H1N1)pdm09 13 IAV strains sampled in 2008–2009 and 2009–2011, respectively, with sequencing conducted in the United States.…”