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Study of factors related to the control of tuberculosis: resistance to drugs, transmission and host susceptibility.

by Baliza Fernandes, Marcilio Delan

Abstract (Summary)
Tuberculosis resurged in the 90s after having been considered to be under control and is nowa serious public health problem with social and economic ramifications. To understand thefactors involved in the transmission and the disease, it is necessary to understand the threefundamentals of the disease: the environment, bacillus and host. This work evaluates thesethree important aspects of the epidemiology of tuberculosis in two municipalities in themetropolitan region of Recife-PE. In the town of Cabo de Santo Agostinho, we characterizedthe pattern of the development of resistant strains and their associated factors. The frequencyof primary and acquired resistance to any drug was 14% and 50%, respectively, while thefrequency of primary and acquired multidrug resistance was 8.3% and 40%, respectively.Previous treatment for tuberculosis and abandonment of treatment were risk factors forprimary resistance to drugs. Among persons with Isoniazid- and Rifampicin-resistant strains,the levels of primary and acquired resistance were quite, making tuberculosis control in Caboquite difficult. The transmission pattern of tuberculosis was defined by using by spoligotypingto genotype strains. A total of 40 distinct patterns were observed: one pattern with 9 isolates,three patterns with 5 isolates each, three other patterns with 4 isolates, two patterns with 3isolates, five patterns with 2 isolates each, and 26 patterns with 1 isolate alone. Geographicalanalysis of cases residing in Cabo compared with those evaluated at the post of Health inLessa de Andrade in Recife (a reference health service for greater Pernambuco) revealed thatboth municipalities shared common isolates. In Recife, the role of genetic markers (HLA) ofhost predisposition to tuberculosis was evaluated among persons who live in the same houseas index cases. Of the 257 subjects studied, 54 persons (reference cases) were not related tothe index case but shared their household. Among the 203 subjects related to the index case,the relative risk for developing tuberculosis, depending on degree of relationship, was 1.22(95%CI :0.75-1 .99) for first-degree, 1.13 (95%CI :0.63-2 .03) for second degree, and 1.11(95%CI :0.44-2 .78) for third degree when compared with the 54 afore-mentioned referencecases. Frequency analysis of HLA class II alleles was conducted separately between the 77individuals who had tuberculosis and the 119 individuals with no history of tuberculosis. Wedid not find any allele associated with susceptibility to illness for tuberculosis. However, theallele DRB5*01 (OR= 0.45; 95%CI= 0.20-0.98; p= 0.0441) appears linked to resistance totuberculosis and the allele DRB3*02 (OR= 0.59; 95%CI= 0.32-1.08; p= 0.0905) shows atrend of association with resistance to develop tuberculosis. A more complete understandingof M. Tuberculosis resistant strains and their genetic polymorphisms, as well as the hostsusceptibility in certain population groups, allow us to better assess the mechanisms ofdisease transmission and ultimately contribute to the control of tuberculosis.
This document abstract is also available in Portuguese.
Bibliographical Information:

Advisor:Maria de Fátima Pessoa Militão de Albuquerque; Norma Lucena Cavalcanti Licínio da Silva

School:Faculdades Oswaldo Cruz

School Location:Brazil

Source Type:Master's Thesis

Keywords:Tuberculosis Drug Resistance HLA Antigens Risk Factors Genotype

ISBN:

Date of Publication:11/23/2007

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