Title: Intestinal infection with Campylobacter in a rural cohort in Moramanga, Madagascar

Background Campylobacter infection is the most common cause of bacterial gastroenteritis in developing countries, as demonstrated by a previous study in Madagascar. Campylobacter is endemic to developing countries and Campylobacter infections seem to lead to the development of protective immunity. We tested this hypothesis in a rural setting in Madagascar, by exploring the association between infection and age, the recurrence of infection and the pathogenicity of Campylobacter. Methods We carried out a cohort study of children under the age of 24 months in Moramanga, with twiceweekly follow-up until the age of 36 months. Results Between January 2010 and May 31 2012, 508 children were included in the cohort. We detected 319 episodes of Campylobacter infection in total, and 43.3% (n=220) of the children had at least one episode of intestinal Campylobacter infection. The rate of Campylobacter isolation from stool specimens was 9.3%, with the highest isolation rates recorded for children aged 6 to 11 months and 12 to 17 months, at 13.4% and 15.2%, respectively. The annual incidence rate for symptomatic Campylobacter infection was 0.05 episodes/child. The probability of 3 Campylobacter infection was highest between the ages of six and 23 months. Taking children under six months of age as the reference group, the age-specific odds ratio for the association was 5.0 (95% CI: 2.9-8.6) for children aged six to 11 months, 5.7 (95% CI: 3.3-10.0) for children aged 12 to 17 months and 3.3 (95% CI: 1.8-5.8) for children aged 18 to 23 months. A second episode of infection occurred 63 days after the first episode in children with primary infections, and after 137 days in children with multiple infections (p<0.01). First episodes of Campylobacter infection were associated with diarrhoea (odds ratio=16.1; 95% confidence interval: 1.8-140.8) Conclusion Our findings suggest that protective immunity to Campylobacter may be acquired over time, following repeated exposure. Care should be paid to children, in the first year of life, as this age seems to be associated with the highest risk of diarrhoea during Campylobacter infection. Our observation raises questions about the priorities for interventions, such as the development of vaccines for prevalent Campylobacter serotypes.