Anti-PGL-1 Positivity as a Risk Marker for the Development of Leprosy among Contacts of Leprosy Cases: Systematic Review and Meta-analysis

Background: There is no point of care diagnostic test for infection with M. Leprae or for leprosy, although ELISA anti PGL-1 has been considered and sometimes used as a means to identify infection. Methods: A systematic review of all cohort studies, which classified healthy leprosy contacts, at entry, according to anti-PGL1 positivity, and had at least one year follow up. The outcome was clinical diagnosis of leprosy by an experienced physician. The meta-analysis used a fixed model to estimated OR for the association of PGL-1 positivity and clinical leprosy. A fixed model also estimated the sensibility of PGL-1 positivity and positive predictive value. Results: Contacts who were anti PGL-1 positive at baseline were 3 times as likely to develop leprosy; the proportion of cases of leprosy that were PGL-1 positive at baseline varied but was always under 50%. Conclusions: Although there is a clear and consistent association between positivity to anti PGL-1 and development of leprosy in healthy contacts, selection of contacts for prophylaxis based on anti PGL1 response would miss more than half future leprosy cases. Should chemoprophylaxis of controls be incorporated into leprosy control programmes, PGL1 appears not to be a useful test in the decision of which contacts should receive chemoprophylaxis. Author Summary: Contacts of leprosy cases are more likely to be infected and develop leprosy. But not everyone infected with M. Leprae develops clinical leprosy. into clinical disease. We examined and summarized all the eight studies that evaluated how well PGL-1 predicts which contacts of leprosy will become cases. PGL-1 positive contacts were 3 times more likely to develop leprosy; a variable proportion, but less than 30% of the cases were attributed to PGL-1 and less than 45% of the PGL-1 contacts developed leprosy. PGL1 would not be an appropriate test to decide which contacts of leprosy should receive preventive therapy if this was proposed in leprosy control programmes.