Host Genetic Factors Affect Susceptibility to Norovirus Infections in Burkina Faso

Abstract

Norovirus (NoV) constitutes the second most common viral pathogen causing pediatric diarrhea after rotavirus. In Africa, diarrhea is a major health problem in children, and yet few studies have been performed regarding NoV. The association of histo-blood group antigens (HBGA) and susceptibility to NoV infection is well established in Caucasian populations with non-secretors being resistant to many common NoV strains. No study regarding HBGA and NoV susceptibility has yet been performed in Africa. We collected 309 stool and 208 saliva samples from diarrheal children in Ouagadougou, Burkina Faso; May 2009 to March 2010. NoV was detected using real-time PCR, and genotyped by sequencing. Saliva samples were ABO, Lewis and secretor phenotyped using in house ELISA assays. NoV was detected in 12% (n = 37) of the samples. The genotype diversity was unusually large; overall the 37 positive samples belonged to 14 genotypes. Only children <2 years of age were NoV positive and the GII.4 NoVs were more frequent in the late dry season (Jan-May). NoV infections were observed less in children with the secretor-negative phenotype or blood group A (OR 0.18; p = 0.012 and OR 0.31; p = 0.054; respectively), with two non-secretors infected with genotypes GII.7 and GII.4 respectively. Lewis-negative (Lea−b−) children, representing 32% of the study population, were susceptible to GII, but were not infected with any NoV GI. GII.4 strains preferentially infected children with blood group B whereas secretor-positive children with blood group O were infected with the largest variety of genotypes. This is the first study identifying host genetic factors associated with susceptibility to NoV in an African population, and suggests that while the non-secretor phenotype provides protection; the Lewis b antigen is not necessary for GII infection.

Causes of Impaired Oral Vaccine Efficacy in Developing Countries

“…While nonsecretors make up just 20% of Caucasians, this phenotype may reach a prevalence of 30-50% in parts of Bangladesh, India and Pakistan [80][81][82], where the immunogenicity and efficacy of oral rotavirus vaccines is poor. Similarly, the Lewis-negative phenotype is significantly more common in parts of Africa (reaching >30% in some populations) than in Caucasians (4-6%) [83]. Thus, an impaired replicative capacity of P[8] strains combined with the high prevalence of P[6] genotypes in Lewis-negative individuals, as reported in Burkina Faso [78], would be consistent with observed discrepancies in rotavirus vaccine efficacy.…”

Association between Norovirus and Rotavirus Infection and Histo-Blood Group Antigen Types in Vietnamese Children

“…Collectively, these two genotypes represented 86.1% of the NoV cases in our study. Occasional infections of nonsecretors by NoV GII.4 and GII.3 strains have been reported (35,41). To our surprise, five children infected with strains belonging to the GII.3c cluster were nonsecretors.…”

“…The preferential infection of secretors by the P [4], P [8], and perhaps P [6] RV genotypes helps explain the predominance of those genotypes in cases of acute gastroenteritis around the world; because most (70 to 80%) of the people in the world are secretors (35,36), there are many susceptible hosts available to infect. Vietnam is no exception.…”

Norovirus GII.17 Predominates in Selected Surface Water Sources in Kenya

“…The two NoV GI.1 strains (KDMarch2012-301 and KDMarch2012-304), detected in the urban Mutoine river, showed a high nucleotide sequence identity (97%) to a clinical NoV GI.1 strain (JX416391) from Burkina Faso. Except for studies in South Africa Murray 2013), Botswana (Mattison et al 2010) and Burkino Faso (Nordgren et al 2013), the occurrence of NoV GI.1 does not appear to be widely reported in Africa as no GI.1 strains were detected in diarrhoeal stool samples from children in Nairobi, Kenya (Mans et al 2014) nor in the clinical specimens (Silva et al 2008;Abugalia et al 2011;Ayukekbong et al 2011;Trainor et al 2013) or sewage samples (Sdiri-Loulizi et al 2010) from other African countries. Norovirus GI.3 however, appears to more prevalent in African regions (Ayukekbong et al 2011;Yassin et al 2012;Trainor et al 2013), including Kenya (Mans et al, 2014).…”

“…Strains of NoV GII.17 were identified in clinical specimens collected during 1999-2000 from human immunodeficiency virus (HIV)-infected children at a care center in Kenya (Mans et al 2014) suggesting that GII.17 has been in circulating in urban and rural Kenyan communities for a number of years. Nucleotide sequence information on NoV GII.17 strains from Burkina Faso (Nordgren et al 2013), Morocco (KJ162374), Cameroon (Ayukekbong et al 2011) and South Africa (Murray et al 2013) are available in GenBank. Although NoV GII.17 seems to be prevalent in some parts of Africa this genotype was not identified in clinical specimens (Silva et al 2008;Abugalia et al 2011;Hassine-Zaafrane et al 2013;Huynen et al 2013;) and environmental samples (Sdiri-Loulizi et al 2010) from many other African regions and the GII.17 predominance appears to be peculiar to Kenya.…”