BackgroundHuman enteroviruses (HEVs) are common causal agents of aseptic meningitis in young children. Laboratory and syndromic surveillance during December 2015 and January 2016 noted an unusually high number of paediatric aseptic meningitis cases at a hospital in Mossel Bay, Western Cape Province, South Africa. HEV was detected in clinical samples, prompting an outbreak investigation.MethodsEpidemiological investigations were conducted to ascertain possible linkage between cases. Amplification, sequencing and phylogenetic analysis of the 5’UTR and VP1 regions was undertaken to determine the HEV serotype associated with the outbreak as well as other cases of aseptic meningitis in the area in the preceding 6 weeks.ResultsOver the 2-month period, 63 CSF samples were available for testing. A total of 43 outbreak cases (68.3%) were observed, and the 26 (60.5%) that could be typed were coxsackie virus A9 (CVA9). Children attending three crèche facilities were epidemiologically linked, accounting for 60.5% (26/43) of the CVA9 cases. The majority of patients were under 10 years of age (55/63, 87.3%) and there was a male predominance (66%). Nucleotide sequence analysis of the 5’UTR and VP1 regions identified 2 lineages of CVA9 co-circulating during the outbreak, although the VP1 capsid protein sequence was identical as all nucleotide differences were synonymous. There was a unique isoleucine at position 64 and all outbreak viruses had a valine to threonine change in the hypervariable BC loop of VP1. Other HEV types circulating in the preceding period were echovirus 30 (n = 4), echovirus 5 (n = 3) and 1 each of echovirus 6, echovirus 9 and echovirus 15.ConclusionCVA9 was identified as the pathogen responsible for the large outbreak of aseptic meningitis, with 2 distinct co-circulating lineages.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3641-4) contains supplementary material, which is available to authorized users.