Latent leprosy infection identified by dual RLEP and anti-PGL-I positivity: Implications for new control strategies

PLoS One. 2021 May 13;16(5):e0251631. doi: 10.1371/journal.pone.0251631. eCollection 2021.

Abstract

The number of new cases of leprosy reported worldwide has remained essentially unchanged for the last decade despite continued global use of free multidrug therapy (MDT) provided to any diagnosed leprosy patient. In order to more effectively interrupt the chain of transmission, new strategies will be required to detect those with latent disease who contribute to furthering transmission. To improve the ability to diagnose leprosy earlier in asymptomatic infected individuals, we examined the combined use of two well-known biomarkers of M. leprae infection, namely the presence of M. leprae DNA by PCR from earlobe slit skin smears (SSS) and positive antibody titers to the M. leprae-specific antigen, Phenolic Glycolipid I (anti-PGL-I) from leprosy patients and household contacts living in seven hyperendemic cities in the northern state of Pará, Brazilian Amazon. Combining both tests increased sensitivity, specificity and accuracy over either test alone. A total of 466 individuals were evaluated, including 87 newly diagnosed leprosy patients, 52 post-treated patients, 296 household contacts and 31 healthy endemic controls. The highest frequency of double positives (PGL-I+/RLEP+) were detected in the new case group (40/87, 46%) with lower numbers for treated (12/52, 23.1%), household contacts (46/296, 15.5%) and healthy endemic controls (0/31, 0%). The frequencies in these groups were reversed for double negatives (PGL-I-/RLEP-) for new cases (6/87, 6.9%), treated leprosy cases (15/52, 28.8%) and the highest in household contacts (108/296, 36.5%) and healthy endemic controls (24/31, 77.4%). The data strongly suggest that household contacts that are double positive have latent disease, are likely contributing to shedding and transmission of disease to their close contacts and are at the highest risk of progressing to clinical disease. Proposed strategies to reduce leprosy transmission in highly endemic areas may include chemoprophylactic treatment of this group of individuals to stop the spread of bacilli to eventually lower new case detection rates in these areas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Bacterial / immunology*
  • Antigens, Bacterial / immunology*
  • Child
  • DNA, Bacterial / analysis
  • Female
  • Glycolipids / immunology*
  • Humans
  • Latent Infection / diagnosis*
  • Latent Infection / immunology
  • Leprosy / diagnosis*
  • Leprosy / immunology
  • Male
  • Middle Aged
  • Mycobacterium leprae / immunology
  • Mycobacterium leprae / isolation & purification*
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • DNA, Bacterial
  • Glycolipids
  • phenolic glycolipid I, Mycobacterium leprae

Grants and funding

This work was supported by CNPq (486183/2013-0 CNPq grant for MBS; 448741/2014-8 grant for JGB and 428964/2016-8 grant and 313633/2018-5 scholarship for CGS); CAPES (BEX 6907/14-8 scholarship for MBS, and 157512-0 scholarship for JGB); CAPES PROAMAZONIA 3288/2013; Fulbright Scholar to Brazil 2015-2016 and 2019-2020 (JSS); and The Heiser Program of the New York Community Trust for Research in Leprosy (JGB, MBS, CGS and JSS) grants P15-000827, P16-000796 and P18-000250. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.