Molecular, immunological and neurophysiological evaluations for early diagnosis of neural impairment in seropositive leprosy household contacts

PLoS Negl Trop Dis. 2018 May 21;12(5):e0006494. doi: 10.1371/journal.pntd.0006494. eCollection 2018 May.

Abstract

Background: Household contacts constitute the highest risk group for leprosy development, and despite significant progress in the disease control, early diagnosis remains the primary goals for leprosy management programs.

Methods: We have recruited 175 seropositive and 35 seronegative household contacts from 2014 to 2016, who were subjected to an extensive protocol that included clinical, molecular (peripheral blood qPCR, slit-skin smear qPCR, skin biopsy qPCR) and electroneuromyographic evaluations.

Results/principal findings: The positivity of peripheral blood qPCR of seropositive contacts was 40.6% (71/175) whereas only 8.6% (3/35) were qPCR positive in seronegative contacts (p = 0.0003). For the slit-skin smear, only 4% (7/175) of seropositive contacts presented positive bacilloscopy, whereas the qPCR detected 47.4% (83/175) positivity in this group compared with only 17.1% (6/35) in seronegative contacts (p = 0.0009). In the ENMG evaluation of contacts, 31.4% (55/175) of seropositives presented some neural impairment, and 13.3% (4/35) in seronegatives (p = 0.0163). The presence of neural thickening conferred a 2.94-fold higher chance of ENMG abnormality (p = 0.0031). Seropositive contacts presented a 4.04-fold higher chance of neural impairment (p = 0.0206). The peripheral blood qPCR positivity presented odds 2.08-fold higher towards neural impairment (OR, 2.08; p = 0.028). Contrarily, the presence of at least one BCG vaccine scar demonstrated 2.44-fold greater protection against neural impairment (OR = 0.41; p = 0.044).

Conclusions/significance: ELISA anti-PGL-I is the most important test in determining the increased chance of neural impairment in asymptomatic leprosy household contacts. The combination of the two assays (ELISA anti-PGL-I and peripheral blood qPCR) and the presence of BCG scar may identify individuals with higher chances of developing leprosy neuropathy, corroborating with the early diagnosis and treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Bacterial / immunology
  • Brazil
  • Enzyme-Linked Immunosorbent Assay
  • Family Characteristics
  • Female
  • Humans
  • Leprosy / diagnosis*
  • Leprosy / immunology
  • Leprosy / microbiology
  • Leprosy / transmission
  • Male
  • Middle Aged
  • Mycobacterium leprae / genetics
  • Mycobacterium leprae / immunology*
  • Mycobacterium leprae / isolation & purification
  • Peripheral Nervous System Diseases / diagnosis
  • Peripheral Nervous System Diseases / immunology
  • Peripheral Nervous System Diseases / microbiology
  • Peripheral Nervous System Diseases / physiopathology*
  • Real-Time Polymerase Chain Reaction
  • Young Adult

Substances

  • Antibodies, Bacterial

Grants and funding

The authors thank the Brazilian funding agencies, Brazilian National Council for Scientific and Technological Development (CNPq) and Foundation for Research Support of the State of Minas Gerais (FAPEMIG), for providing financial support to the National Institute of Science and Technology in Theranostics and Nanobiotechnology – INCT-TeraNano – LRG (Grant numbers CNPq 465669/2014-0 and FAPEMIG-CBB-APQ-03613-17). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.