Disease dynamics in patients with drug-resistant tuberculosis residing in a high incidence community

[摘要] ENGLISH ABSTRACT:Drug-resistant tuberculosis poses a threat to global tuberculosis control by theWHO DOTS strategy. Studies in the United States and Europe have shown (i) thatdrug-resistant tuberculosis is present in every country; (ii) that, by contrast to previousdogma, drug-resistant bacilli are virulent and can be transmitted, especially ininstitutional settings and to immunocompromised patients; and (iii) that the majorityof cases arise by acquisition of drug resistance due to errors in the management of TBcases. (iv) Furthermore, it has been shown that the extremely high case fatality ratesof the 1980s and early 1990s can be reduced by individualized, but costly treatment.However, the majority of drug-resistant TB cases reside in the developing world.Data on disease epidemics in less developed parts of the world are scarce. The aim ofthis thesis was to study the disease dynamics of drug-resistant TB in a developingcountry where TB is endemic.All cases of drug-resistant TB during a 5-year period in two communities withpoor socioeconomic living conditions were included for this observational study.Three different methods were used: restriction fragment length polymorphism(RFLP), mutation detection analysis by dot-blot hybridisation technique and aGeographic Information System. Results of RFLP analysis and mutation detectionanalysis showed that community outbreaks of drug-resistant Mycobacteriumtuberculosis strains occur, even without the involvement of immunocomprimisedpatients. Infection with a drug-resistant strain occurred in new patients (primary drugresistance) as well as in patients treated before (exogenous reinfection). Exogenousreinfection was also shown to be an important mechanism of recurrence after previouscure for drug-sensitive TB. Transmission of drug-resistant strains occurred morefrequent in areas with lower socioeconomic living conditions. The relativecontribution of transmission differed substantially between the group of multi drugresistant(two thirds of cases) and single-drug-resistant (no cases) cases, whichprobably reflects the prolonged infectiousness of multi drug-resistant cases. To stopthe growing epidemic of multi drug-resistant TB, prevention of acquisition as well astransmission of drug-resistant tuberculosis will be required. This will only be possiblein areas where a DOTS strategy is well functioning and with a modification of centralelements of the standard DOTS mechanism: a DOTS-plus strategy. Early andaccurate diagnosis of drug resistance is essential for effective management. Diagnosisbased on two direct smear tests might have to be replaced by routine drugsusceptibilitytests at diagnosis. Because the routine performance of phenotypic drugsusceptibilitytests was inferior to the performance of genotypic tests, thedevelopment of an affordable commercial kit testing a limited number of mutationsconferring resistance could be of great value in the global fight against multidrugresistantTB. Because of the importance of early diagnosis, selective active contacttracing for multidrug-resistant cases, additional to the routine passive contact tracing,could prove to be cost-effective. Individualized treatment regimens are effective inreducing the failure rate, mortality and probably transmission of multidrug-resistantTB.Multidrug-resistant tuberculosis is a problem confronting the efforts for globaltuberculosis control. Efficient strategies to turn the tide exist, but internationalpolitical commitment and financial support will be essential.

[发布机构] Stellenbosch University