Thesis (PhD)--Stellenbosch University, 2000. / ENGLISH ABSTRACT: Drug-resistant tuberculosis poses a threat to global tuberculosis control by the
WHO DOTS strategy. Studies in the United States and Europe have shown (i) that
drug-resistant tuberculosis is present in every country; (ii) that, by contrast to previous
dogma, drug-resistant bacilli are virulent and can be transmitted, especially in
institutional settings and to immunocompromised patients; and (iii) that the majority
of cases arise by acquisition of drug resistance due to errors in the management of TB
cases. (iv) Furthermore, it has been shown that the extremely high case fatality rates
of 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 of
this thesis was to study the disease dynamics of drug-resistant TB in a developing
country where TB is endemic.
All cases of drug-resistant TB during a 5-year period in two communities with
poor 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 a
Geographic Information System. Results of RFLP analysis and mutation detection
analysis showed that community outbreaks of drug-resistant Mycobacterium
tuberculosis strains occur, even without the involvement of immunocomprimised
patients. Infection with a drug-resistant strain occurred in new patients (primary drug
resistance) as well as in patients treated before (exogenous reinfection). Exogenous
reinfection was also shown to be an important mechanism of recurrence after previous
cure for drug-sensitive TB. Transmission of drug-resistant strains occurred more
frequent in areas with lower socioeconomic living conditions. The relative
contribution of transmission differed substantially between the group of multi drugresistant
(two thirds of cases) and single-drug-resistant (no cases) cases, which
probably reflects the prolonged infectiousness of multi drug-resistant cases. To stop
the growing epidemic of multi drug-resistant TB, prevention of acquisition as well as
transmission of drug-resistant tuberculosis will be required. This will only be possible
in areas where a DOTS strategy is well functioning and with a modification of central
elements of the standard DOTS mechanism: a "DOTS-plus" strategy. Early and accurate diagnosis of drug resistance is essential for effective management. Diagnosis
based on two direct smear tests might have to be replaced by routine drugsusceptibility
tests at diagnosis. Because the routine performance of phenotypic drugsusceptibility
tests was inferior to the performance of genotypic tests, the
development of an affordable commercial kit testing a limited number of mutations
conferring resistance could be of great value in the global fight against multidrugresistant
TB. Because of the importance of early diagnosis, selective active contact
tracing for multidrug-resistant cases, additional to the routine passive contact tracing,
could prove to be cost-effective. Individualized treatment regimens are effective in
reducing the failure rate, mortality and probably transmission of multidrug-resistant
TB.
Multidrug-resistant tuberculosis is a problem confronting the efforts for global
tuberculosis control. Efficient strategies to turn the tide exist, but international
political commitment and financial support will be essential. / AFRIKAANSE OPSOMMING: Middel weerstandige tuberkulose hou 'n bedreiging in vir globale tuberkulose
kontrole deur die WGO DOTS strategie. Studies in die Verenigde State en Europa het
getoon (i) dat middel weerstandige tuberkulose in alle lande voorkom; (ii) dat, in
teenstelling met vorige dogma, middel weerstandige bakterieë virulent is en oorgedra
kan word, veral in inrigtings en aan immuun-onderdrukte pasiënte; en (iii) dat die
meeste gevalle ontstaan deur die verwerwing van middel weerstandigheid a.g.v. die
foutiewe hantering van tuberkulose gevalle. (iv) Bykomend is getoon dat die
ontsettende hoë mortaliteit syfers van die 1980s verlaag kan word deur geindividualiseerde,
maar duur behandeling.
Die meeste middel weerstandige tuberkulose gevalle woon egter in die
ontwikkelende wêreld. Data oor siekte epidemies in minder ontwikkelde dele van die
wêreld is skaars. Die doel van hierdie tesis was om die siekte dinamiek van middel
weerstandige tuberkulose te bestudeer in 'n ontwikkelende land waar tuberkulose
endemies is.
Alle gevalle van middel weerstandige tuberkulose gedurende 'n 5-jaar periode in
twee lae sosio-ekonomiese gemeenskappe, is in hierdie studie ingesluit. Drie
verskillende metodes is gebruik: restriksie fragment lengte polimorfisme (RFLP),
mutasie analise deur dot-blot hibridisasie en 'n Geografiese Inligting Stelsel.
Resultate van die RFLP analise het getoon dat uitbrake van middel weerstandige
Mycobacterium tuberculosis stamme in die gemeenskap voorkom, selfs sonder die
aantasting van immuun-onderdrukte pasiënte. Infeksie met middel weerstandige
stamme het voorgekom in nuwe pasiënte (primêre middel weerstandigheid) en ook in
pasiënte wat reeds voorheen behandel is (eksogene herinfeksie ). Daar is ook gevind
dat eksogene herinfeksie 'n belangrike meganisme was van herhaalde tuberkulose na
vorige genesing van middel sensitiewe tuberkulose. Die oordrag van middel
weerstandige stamme het meer dikwels voorgekom in areas met laer sosioekonomiese
omstandighede. Die relatiewe bydrae van oordrag het merkwaardig
verskil tussen multi-middel weerstandigheid (twee derdes van gevalle) en enkelmiddel
weerstandigheid (geen gevalle). Dit weerspieël waarskynlik die verlengde
periode van infektiwiteit van die multi-middel weerstandige gevalle. Die bekamping
van die groeiende epidemie van multi-middel weerstandige tuberkulose, vereis die
voorkoming van verworwe sowel as oorgedraagde middel weerstandige tuberkulose. Dit sal slegs moontlik wees in areas waar 'n DOTS strategie reeds goed funksioneer
en met 'n aanpassing van die sentrale elemente van die roetine DOTS meganisme: 'n
"DOTS-plus" strategie. Vroeë en akkurate diagnose van middel weerstandigheid is
essensieël vir effektiewe hantering. Diagnose gebaseer op twee direkte sputum smeer
toetse mag moontlik vervang moet word deur roetine middel sensitiwiteit bepalings
by diagnose. Die roetine fenotipiese middel sensitiwiteit bepaling is gevind om
minderwaardig te wees in vergelyking met die genotipiese toetse. Die ontwikkeling
van 'n bekostigbare toetsstelsel wat die mees algemene mutasies vir middel
weerstandigheid sal opspoor, kan van groot waarde wees in die stryd teen mutimiddel
weerstandige tuberkulose. Aangesien vroeë diagnose so belangrik is, kan
aktiewe kontak opsporing koste-effektief wees. Ge-individualiseerde
behandelingskedules is effektief om die sukses van behandeling en oorlewing te
verbeter, en moontlik ook om die oordrag van multi-middel weerstandige tuberkulose
te verminder.
Multi-middel weerstandige tuberkulose is 'n probleem vir die globale kontrole van
tuberkulose. Effektiewe strategieë om die vloed te stuit, bestaan, maar politieke
verbintenis en geldelike ondersteuning sal essensieël wees.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/51732 |
| Date | 12 1900 |
| Creators | Van Rie, Annelies |
| Contributors | Beyers, N., Van Helden, P., Stellenbosch University. Faculty of Medicine & Health Sciences. Dept. of Paediatrics & Child Health. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Format | 165 p. : ill. |
| Rights | Stellenbosch University |
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