Detection and molecular characterisation of noroviruses in hospitalised children in Malawi, 1997-2007.

Despite the increasing recognition of noroviruses as major pathogens associated with community-acquired diarrhoea in children, there are few studies from Africa. Long-term surveillance studies of rotavirus gastroenteritis in Malawian children have provided an opportunity to undertake a study of the importance and epidemiological features of norovirus infection in this population. Faecal specimens were collected from children <5 years of age admitted to hospital with acute diarrhoea, as well as from a comparison group of diarrhoea-free children, in Blantyre, Malawi between 1997 and 2007. Norovirus was detected using real-time PCR and strains genotyped by nucleotide sequence analysis. Norovirus was detected in 220/1,941 (11.3%) faecal specimens, comprising genogroup GI (1.8%), GII (9.4%) and mixed GI/GII (0.1%). The median age of children with norovirus was 6 months (range, 0-48 months). Norovirus was detected throughout the year, with peaks at the end of the rainy season (March) and towards the end of the dry season (August-November). Norovirus GII.4 was the most commonly detected genotype accounting for 70% of strains characterised, followed by GII.2 (6%), GII.6 (4%) and GII.12 (4%). Sub typing of GII.4 noroviruses demonstrated local circulation of strains prior to their subsequent detection in association with global epidemics of gastroenteritis. The prevalence of norovirus in children without diarrhoea was similar to the level in cases. This largest study to date of norovirus infection in African children indicates the potential role of paediatric surveillance in predicting the emergence of norovirus strains with global epidemic potential.

Detection of enterotoxigenic E. coli in hospitalised children with and without diarrhoea in Blantyre, Malawi.

BACKGROUND: Enterotoxigenic E. coli (ETEC) is an important cause of diarrhoea among children in developing countries. The burden of ETEC infection was investigated for the first time in children in Malawi. METHODS: Faecal samples obtained from children < 5 years of age hospitalised with diarrhoea in Blantyre, Malawi over a 10-year period (1997-2007) before introduction of the rotavirus vaccine were examined by PCR for ETEC heat-labile (LT) and heat-stable (STh and STp) enterotoxins. Children hospitalised without diarrhoea were enrolled over a 2-year period as a comparison group. RESULTS: ETEC was detected in 205 (10.6%) of 1941 children with diarrhoea. The most prevalent toxin type was STh (6·6%), followed by LT (2·1%) and STp (0·9%). ETEC infection was most prevalent in infants aged 6-11 months. Co-infection with rotavirus was common. ETEC was detected in 37 (7·3%) of 507 children without diarrhoea. CONCLUSION: The burden of ETEC infection in young Malawian children is substantial and should become a focus of diarrhoea prevention efforts in the post-rotavirus vaccine era.

Early Detection of Epidemic GII-4 Norovirus Strains in UK and Malawi: Role of Surveillance of Sporadic Acute Gastroenteritis in Anticipating Global Epidemics.

Noroviruses are endemic in the human population, and are recognised as a leading cause of acute gastroenteritis worldwide. Although they are a highly diverse group of viruses, genogroup-II genotype-4 (GII-4) noroviruses are the most frequently identified strains worldwide. The predominance of GII-4 norovirus strains is driven by the periodic emergence of antigenic variants capable of evading herd protection. The global molecular epidemiology of emerging GII-4 strains is largely based on data from outbreak surveillance programmes, but the epidemiology of GII-4 strains among sporadic or community cases is far less well studied. To understand the distribution of GII-4 norovirus strains associated with gastroenteritis in the wider population, we characterised the GII-4 norovirus strains detected during studies of sporadic cases of infectious gastroenteritis collected in the UK and Malawi between 1993 and 2009. Our data shows that GII-4 norovirus strains that have emerged as strains of global epidemic importance have circulated in the community up to 18 years before their recognition as pandemic strains associated with increases in outbreaks. These data may suggest that more comprehensive surveillance programmes that incorporate strains associated with sporadic cases may provide a way for early detection of emerging strains with pandemic potential. This may be of particular relevance as vaccines become available.

Molecular epidemiology of noroviruses associated with acute sporadic gastroenteritis in children: global distribution of genogroups, genotypes and GII.4 variants.

Noroviruses are a leading cause of epidemic and sporadic acute gastroenteritis worldwide. The development of sensitive molecular diagnostic techniques has revolutionized our understanding of norovirus epidemiology over the past two decades, but norovirus strain types associated with sporadic gastroenteritis remain poorly described. Therefore, we conducted a systematic review of studies performed after 2000 to clarify the genotypic distribution of noroviruses in children (≤18 years of age) with sporadic acute gastroenteritis. Genogroup GII norovirus was the most prevalent, accounting for 96% of all sporadic infections. GII.4 was the most prevalent genotype, accounting for 70% of the capsid genotypes and 60% of the polymerase genotypes, followed by the capsid genotype GII.3 (16%) and the polymerase genotype GII.b (14%). The most common ORF1/ORF2 inter-genotype recombinants were GII.b, GII.12, and GII.4 polymerase genotypes combined with the capsid genotype GII.3, accounting for 19% of all genotyped strains. The distribution of GII.4 variants over the last decade was dominated by successive circulation of GII.4/2002, GII.4/2004, GII.4/2006b, and GII.4/2008 with GII.4/2006b continuing to date. Genotypes GII.4 and GII.3 have predominated in children during the past decade; this is most notable in the global emergence of GII.4 variant noroviruses. As the burden of rotavirus disease decreases following the introduction of childhood immunization programs, the relative importance of norovirus in the etiology of acute childhood gastroenteritis will likely increase. In order for a successful norovirus vaccine to be developed, it should provide immunity against strains with capsid genotypes GII.4 and GII.3.