Serological Measures of Trachoma Transmission Intensity

Active disease, defined as trachomatous inflammation–follicular (TF) or trachomatous inflammation–intense (TI), is self-limiting, but repeated infections can lead to pathology in the form of scarring (TS); trichiasis (TT), distinguishable by turned-in eyelashes rubbing against the globe of the eye; and irreversible blindness caused by corneal opacity (CO). Global efforts to eliminate trachoma as a public health problem by the year 2020 are based on the SAFE strategy: surgery for treatment of trichiasis, mass drug administration of antibiotics, and promotion of facial cleanliness and environmental improvement. Serological tests for post-endemic surveillance of trachoma elimination programs have been examined. Antibody responses to the Ct antigens pgp3 and CT694 show high sensitivity and specificity for Ct infection. A large percentage of children living in trachoma-endemic communities have detectable antibody responses but exhibit no clinical signs and lack bacterial nucleic acid in the conjunctiva, suggesting that these responses are indicators of historical rather than active infection. No seroreversion was observed in seropositive individuals examined six months after drug treatment, although statistically significant decreases in antibody levels to pgp3 and CT694 were observed in younger age groups. Studies were conducted in the Kongwa District of Tanzania as part of two separate studies in collaboration with the Kongwa Trachoma Project. The first study evaluated the impact of alternative models of community-wide treatment with azithromycin and to compare nucleic acid amplification test methods in a hyperendemic community. The second study evaluated the health impact of an integrated NTD program on non-targeted diseases in mesoendemic and hypoendemic communities. Children 1–6 years of age were recruited from a single hyperendemic community and children 1–9 years of age were recruited from eight villages each to comprise the mesoendemic and hypoendemic communities. Clinical examinations for TF were performed by experienced graders, and dried blood spots (DBS) and conjunctival eye swabs for PCR were collected. Parents or guardians provided written informed consent for children participating in the study, and children over 7 provided verbal assent. The study was approved by The Institutional Review Boards of the Tanzanian National Institute for Medical Research, Centers for Disease Control and Prevention, and Johns Hopkins University School of Medicine. The basic reproduction number (R0) was calculated to estimate the transmission potential using a simple method that assumes a constant force of infection (cFOI) over age. The proportion of the population at age a that is seronegative (Sa) is given by the integral of the force of infection at age x (λ(x)) from 0 to a. Assuming that the force of infection is constant with age, R0 can be approximated as λ/L, where L is the average lifespan of the population, which was set to 75 years. This value of the lifespan may not correspond exactly with the true average life expectancy across the regions from which data were collected.