Shining light on the dark matter of pertussis: evidence for an asymptomatic carriage state from a longitudinal cohort of mother/infant dyads

Pertussis remains an enigma partly due to the uncertain impact of asymptomatic cases on transmission. Contributing to this knowledge gap is a lack of high-quality disease surveillance, particularly in those low- and middle-income countries that experience high disease burdens. Here we present analyses based on our prospective longitudinal surveillance of a rolling cohort of 1,315 mothers and their newborn infants in Lusaka, Zambia across 2015 (8,704 unique study visits). We detail the timing, duration, and intensity of qPCR-based IS481 signals in individual subjects and within mother/infant dyads. We find that IS481 signal strength: A) in mothers predicts contemporaneous and future IS481 detections in infants, B) in infants predicts, to a lesser extent, detections in mothers, and C) predicts respiratory symptoms in infants but not mothers. We profile a subgroup of 50 infants and 54 mothers who displayed evidence of persistent colonization (median duration 8 weeks) wherein most mothers were entirely asymptomatic. We also include a critical assessment of qPCR test reliability across IS481 signal strengths. Our results indicate that pertussis transmission routinely occurs between minimally symptomatic mothers and their newborn infants, and demonstrate the routine occurrence of long-duration, mild and minimally symptomatic pertussis infections.