Molecular and Immunological Tools for Detection of Strain Diversity, Drug Resistance and Immunological Responses
Condition: Leprosy
MeSH terms: Leprosy
Study type: Observational

Summary: 
      The purpose of this study is to determine what factors contribute to the continued incidence
      of leprosy in Colombia. Study participants will include volunteering and consenting
      individuals, older than 4 years of age, representing three study groups:

        1. healthy persons with no known contact with leprosy patients

        2. patients reporting at Instituto Colombiano de Medicina Tropical-CES and Impresa Social
           del Estado Sanatorio Agua de Dios with a new diagnosis of leprosy or relapse of leprosy

        3. household contacts of leprosy patients described in group 2. Blood, nasal swabs, slit
           skin smears, and biopsies will be taken from the volunteers to learn the strains of
           leprosy-causing bacteria in the area, the immune responses (body's response to disease)
           in local residents against the bacteria, and the pattern of leprosy transmission.
           Individuals will participate in this study for 1-10 days, and the study will last for 3
           years.
    

Detailed description: 
      The overall objectives of this study are to understand the factors leading to continued
      incidence of leprosy in Colombia by novel molecular methodologies using a combination of
      retrospective and prospective sampling approaches using three study groups. Specific
      objectives are: (1) strain typing of M. leprae isolates obtained from newly diagnosed leprosy
      patients and household contacts (HHCs) in Colombia to identify clusters and transmission
      patterns when combined with conventional epidemiological criteria; (2) to determine the
      viability of M. leprae by mRNA detection in specimens collected from new leprosy patients and
      HHCs; (3) to identify and determine the extent of mutations conferring resistance in past and
      circulating M. leprae isolates from leprosy patients to two Multidrug therapy (MDT) drugs;
      dapsone and rifampicin; (4) to detect chains of transmission in endemic populations by a
      retrospective analyses of isolates in sample banks when combined with strain typing
      information from new cases and conventional epidemiological criteria; and (5) to detect,
      compare, and delineate immune response profiles to M. leprae antigens as biomarkers for early
      detection of leprosy and prediction of clinical outcome (susceptible, infected, and resistant
      individuals) among three study groups. Study participants for prospective sample collections
      will include volunteering and consenting individuals older than 4 years of age, representing
      three study groups: (1) healthy persons with no known contacts with leprosy patients, (2)
      patients reporting at Instituto Colombiano de Medicina Tropical-CES (ICMT-CES) and Impresa
      Social del Estado Sanatorio Agua de Dios for the diagnosis of leprosy and/or relapse of
      leprosy, and (3) household contacts (HHC) of leprosy patients reporting at Instituto
      Colombiano de Medicina Tropical-CES (ICMT-CES) and Impresa Social del Estado Sanatorio Agua
      de Dios. Blood, nasal swabs, slit skin smears and biopsies will be obtained prospectively
      from individuals greater than 4 years of age representing three study groups: newly diagnosed
      and relapse leprosy patients, their household contacts; and healthy persons with no known
      contacts with leprosy patients. Retrospective archived samples from past and present leprosy
      patients will be included when available. DNA and RNA based methodologies will be developed
      and applied to obtain data necessary for substantiation of a number of factors implicated in
      transmission of leprosy in Colombia. Nucleic acid based molecular methods like Multiple Locus
      Variable number of tandem repeat Analysis (MLVA) and Single Nucleotide Polymorphisms (SNPs)
      will be performed for strain typing M. leprae, in combination with epidemiological
      information to delineate the distribution of types of the organism in various regions of
      Colombia. Other DNA markers such as mutations causing drug resistance will also be collected
      from the M. leprae containing specimens. Due to the lack of methods to cultivate M. leprae,
      viability of the organism in newly collected biological samples will be tested by mRNA
      detection. A database will be generated which will include M. leprae genotypes, patient
      history (clinical and demographic) for comprehensive epidemiological analyses to monitor
      prevailing M. leprae population structures reflective of short and long range dissemination;
      and correlations between disease type and genotype; to track evolutionary and transmission
      patterns. Profiling of host immunological responses during infection with M. leprae will be
      done by detection of a panel of cytokines at the level of mRNA and/or protein, and detection
      of antibodies against M. leprae antigens in leprosy patients, their household contacts and
      healthy individuals with no known history or contacts with leprosy patients.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Study participants for prospective sample collections will include volunteering and
        consenting individuals older than 18 years of age, representing three study groups
      
Biospecimen description: 
      Blood, Nasal Swabs, Skin Biopsies and scrapings
    
Keywords: leprosy; Colombia