title: Clinical manifestations of leprosy after BCG vaccination: an observational study in Bangladesh.
abstract: BACKGROUND
  Although BCG is used as a vaccine against tuberculosis, it also protects against leprosy. Previous evaluation over 18 years of an intervention of two doses BCG for 3536 household contacts of leprosy patients showed that 28 (23%) out of 122 contacts diagnosed with leprosy, developed symptoms 2-10 months after vaccination. This study describes contacts of leprosy patients in Bangladesh who developed leprosy within 12 weeks after receiving a single BCG dose.
  
  
  METHODS
  A cluster RCT in Bangladesh aims to study the effectiveness of the BCG vaccine versus BCG in combination with single dose rifampicin (SDR) given 2 to 3 months after BCG, in the prevention of leprosy among contacts of newly diagnosed leprosy patients. During the first 1,5 years of this ongoing trial we identified contacts who developed leprosy within the first 12 weeks after receiving BCG vaccination, the timeframe before SDR is given.
  
  
  RESULTS
  We identified 21 contacts who developed leprosy within 12 weeks after BCG vaccination among 5196 vaccinated contacts (0.40%). All 21 cases presented with paucibacillary (PB) leprosy, including children and adults. About half of these cases had previously received BCG vaccination as indicated by the presence of a BCG scar; 43% presented with signs of nerve function impairment and/or Type 1 (reversal) reaction, and 56% of the index patients had multibacillary (MB) leprosy.
  
  
  CONCLUSIONS
  An unexpectedly high proportion of healthy contacts of leprosy patients presented with PB leprosy within 12 weeks after receiving BCG vaccination, possibly as a result of boosted cell-mediated immunity by homologues of Mycobacterium leprae antigens in BCG. Various immunological mechanisms could underlie this phenomenon, including an immune reconstitution inflammatory syndrome (IRIS). Further studies are required to determine whether BCG vaccination merely altered the incubation period or actually changed the course of the infection from self-limiting, subclinical infection to manifest disease.
authors.affiliation: Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Renate A
authors.initials: RA
authors.lastname: Richardus
authors.affiliation: Rural Health Program, The Leprosy Mission International Bangladesh, Nilphamari, Bangladesh.
authors.forename: C Ruth
authors.initials: CR
authors.lastname: Butlin
authors.affiliation: Rural Health Program, The Leprosy Mission International Bangladesh, Nilphamari, Bangladesh.
authors.forename: Khorshed
authors.initials: K
authors.lastname: Alam
authors.affiliation: Rural Health Program, The Leprosy Mission International Bangladesh, Nilphamari, Bangladesh.
authors.forename: Kallyan
authors.initials: K
authors.lastname: Kundu
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Geluk
authors.affiliation: Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: j.richardus@erasmusmc.nl.
authors.forename: Jan Hendrik
authors.initials: JH
authors.lastname: Richardus
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use; D001459:Bangladesh; D002648:Child; D004359:Drug Therapy, Combination; D005191:Family Characteristics; D005260:Female; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000209:etiology; D007111:Immunity, Cellular; D007917:Leprostatic Agents / Q000008:administration & dosage; D056005:Leprosy, Paucibacillary / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology*; D012293:Rifampin / Q000008:administration & dosage*; D014611:Vaccination; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D007917:Leprostatic Agents; D012293:Rifampin
keywords: BCG; Contacts; Leprosy; M. leprae; Prevention; Prophylaxis