Acquisition and Clearance Dynamics ofCampylobacterin Children in Low- and Middle-Income Countries

Summary Background The burden of Campylobacter infection is high in children under five years of age in low- and middle-income countries (LMIC), but its acquisition and clearance process is understudied due to scarcity of longitudinal data. We aim to quantify this process using a statistical modeling approach, leveraging data from a multi-nation study. Methods Motivated by the MAL-ED study in which children from eight low- and middle- income countries were followed up for enteric infections during their first two years of life, we developed a two-stage Markov model to compare the dynamics of acquisition and clearance of Campylobacter in children across countries and to explore antibiotic effectiveness on Campylobacter clearance. This model was validated using simulations and applied to the longitudinal data from MAL-ED. Findings The clearance rate was higher than the acquisition rate at most sites and times, but the temporal trend of these rates varied across countries. For Campylobacter jejuni/coli , clearance was faster than acquisition under two years of age at all sites. For Campylobacter spp., the acquisition rate surpassed the clearance rate in the second half of the first year in Bangladesh, Pakistan and Tanzania, leading to high prevalence in these countries. Bangladesh had the shortest (28 and 57 days) while Brazil had the longest (328 and 306 days) mean times to acquisition for Campylobacter spp. and C. jejuni/coli , respectively. South Africa had the shortest (10 and 8 days) while Tanzania had the longest (53 and 41 days) mean times to clearance for Campylobacter spp. and C. jejuni/col respectively. The use of macrolides was associated with accelerated clearance of C. jejuni/coli in Bangladesh and Peru and of Campylobacter spp. in Bangladesh and Pakistan. The use of fluoroquinolones showed statistically meaningful effectiveness only in Bangladesh but for both C. jejuni/coli and Campylobacter spp. Interpretation Higher burden of Campylobacter infection was mainly driven by high acquisition rate that was close to or surpassing the clearance rate. Acquisition usually peaked in 11-17 months in the LMIC setting, indicating the importance of targeting the first year of life for effective intervention. Funding Bill & Melinda Gates Foundation.