Prospective Study of Serological Conversion as a Risk Factor for Development of Leprosy among Household Contacts

Abstract

Although the prevalence of leprosy has declined over the years, there is no evidence that incidence rates are falling. A method of early detection of those people prone to develop the most infectious form of leprosy would contribute to breaking the chain of transmission. Prophylactic treatment of serologically identified high-risk contacts of incident patients should be an operationally feasible approach for routine control programs. In addition, classification of high-risk household contacts will allow control program resources to be more focused. In this prospective study, we examined the ability of serology used for the detection of antibodies to phenolic glycolipid I of Mycobacterium leprae to identify those household contacts of multibacillary leprosy patients who had the highest risk of developing leprosy. After the start of multidrug therapy for the index case, a new case of leprosy developed in one in seven of the 178 households studied. In households where new cases appeared, the seropositivity rates were significantly higher (P < 0.001) than those in households without new cases. Seropositive household contacts had a significantly higher risk of developing leprosy (relative hazard adjusted for age and sex [aRH], 7.2), notably multibacillary leprosy (aRH ‫؍‬ 24), than seronegative contacts.

Unveiling healthy carriers and subclinical infections among household contacts of leprosy patients who play potential roles in the disease chain of transmission

“…This assumption is further supported by the HHCs data, in which 13% tested positive for IgM anti-PGL-I, a higher percentage than that observed in TT patients, with an increasing prevalence of positive results for MB forms of leprosy. These results further corroborate other studies that demonstrated anti-PGL-I seropositivity is a high risk factor for the development of disease in HHCs, mainly contacts of MB ICs (Douglas et al 2004, Goulart et al 2008). …”

Factors associated with seropositivity for APGL-Iamong household contacts of leprosy patients

“…In a prospective study, healthy HC with leprosy were followed-up for 12 years. The authors found that APGL-I-positive individuals had 7.65 times higher risk of exhibiting leprosy signs than the APGL-I-negative individuals, and they had a much higher risk for developing MB leprosy (34.4 times) than that for developing PB leprosy (3.52 times) (15) . These results indicate that in the eventual initiation of chemoprophylaxis for HC by the World Health Organization (WHO) (16) , APGL-I-positive HC would be the key focus for reducing leprosy transmission rates.…”

The potential for vaccination in leprosy elimination: new tools for targeted interventions

“…In addition, the presence of antibodies against PGL-I in contacts was associated with a relative risk factor of six times that of negative contacts in Uberlândia (Goulart et al 2008). An examination of serum samples collected from patient contacts in the Philippines also indicated that elevated or rising antibody levels against PGL-I and LID-1, a chimeric fusion protein comprising ML2331 and ML0405, were predictive of the clinical onset of leprosy (Douglas et al 2004, Duthie et al 2007). The time benefit over clinical diagnosis provided by recognising elevated anti-LID-1 IgG levels was estimated to be approximately nine months (Fig.…”

“…This seropositive but asymptomatic group is perhaps the most interesting to analyse from the viewpoint of reducing infectious reservoirs and the transmission cycle, but has been largely included only serendipitously in prior studies by virtue of being enriched for HHC (i.e., more HHC are seropositive than the general population, although they have typically been included in studies because they are contacts and not because they are seropositive). Although antibody responses in asymptomatic individuals will likely be lower than in patients with high M. leprae burdens, elevated antibody responses appear to indicate an increased risk of developing leprosy, particularly with responses that increase over time (Douglas et al 2004, Duthie et al 2007 (Fig. 1A).…”