No description available.

Thesis (MSc (Community Health))--University of Stellenbosch. 1995. / Please refer to full text for abstract

Tuberculosis (TB) is one of the most prevalent infectious diseases worldwide and causes high morbidity and mortality, despite the widespread availability of effective antibiotics against most strains of Mycobacterium tuberculosis, which is the causative agent of TB. One of the primary reasons that hinder TB control is that many cases of active disease go undetected or are discovered late. This is, in large part, due to the relative insensitivity and limited specificity, amongst other limitations, of the current TB diagnostics tests. Moreover, M. tuberculosis infection can be asymptomatic and latent, or cause active disease. Therefore, an ideal or effective TB diagnostic needs to distinguish between these two states. The aim of this study was to develop novel diagnostic reagents for M. tuberculosis using phage displayed peptides and nucleic acid aptamers with a view to discerning latent from active TB. Using a linear (X12) and constrained (CX7C) phage display libraries, five rounds of selection (biopanning) were performed. Ten phage displayed peptides that bind to the mycobacteria surface were selected. These phage clones were identified using both random clone picking and high throughput (HTP) sequencing. A phage clone displaying the CPLHARLPC peptide was identified by HTP sequencing as the most enriched, representing 82.49% of the selected CX7C phage population. Further characterization showed that it bound better to different mycobacteria species, including M. tuberculosis, than the unselected phage library. Moreover, using surface plasmon resonance (SPR) technology, the chemically synthesised CPLHARLPC peptide was shown to bind M. tuberculosis H37Rv whole cell lysate and not non-mycobacteria lysates. In addition, using the systematic evolution of ligands by exponential enrichment (SELEX) protocol and SPR technology, 2'-Fluoro-pyrimidine-RNA aptamers were selected against the mycobacteria ESX-3 secreted protein, ESX-G. At least five aptamers were identified after five rounds of selection. Two of these aptamers, GH43 and GH78, not only bound EsxG with high affinities, KD 8.04 ± 1.90 nM and KD 78.85 ±9.40 nM respectively, but also preferentially bound EsxG better than the EsxA homologue. Taken together, these findings suggest that a combination of phage display, SELEX and HTP sequencing can be a useful tool for the identification of specific detection reagents that can bind to mycobacteria and its associated targets. These reagents could be exploited to develop alternative molecular probes for TB diagnostics. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2013.

The Tuberculosis infection rate has been generally escalating due to poor health conditions in the Gweru district of Zimbabwe. The study therefore seeks to identify the risk factors that affect TB treatment in the Gweru district. A cross sectional study was carried out in which a questionnaire was employed for data collection on 113 respondents. A binary logistic regression model was employed for data analysis. A total of 98 TB patients were interviewed: [50 respondents (44.0%) had Multi-drug resistant Tuberculosis and 63 respondents (56.0%) had general Tuberculosis). Before being enrolled into the study, an informed consent form was given to each of the participants. The data was then put into excel and later transferred to SPSS for analysis. Out of the 14 potential risk factors of TB treatment, only 6 variables (side effects, gender, alcohol use, HIV status, smoking during the treatment period and having been pre-exposed to TB drugs) were statistically significant in their association with treatment failure.

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.

Thesis (MD)--University of Stellenbosch, 2002. / ENGLISH ABSTRACT: Resistance to antituberculosis agents became evident soon after antituberculosis treatment was introduced for the first time. Combined drug therapy seemed to resolve this problem. Animal experimental studies, which showed that isoniazid (INH)-resistant strains of Mycobacterium tuberculosis were less infectious and pathogenic than drugsusceptible strains, gave further reassurance that drug resistance was not a major issue. Transmission of INH- and multiple-drug-resistant strains did, however, occur. Studies in children, who develop mainly primary drug resistant tuberculosis (TB), showed that drug resistance in adults was followed by a similar rise in drug-resistant (TB) in children, and that tuberculous infection rates in childhood contacts of INHresistant and drug-susceptible adult TB cases were the same. It was however, only after the significant rise in the incidence of TB and large outbreaks of multidrug-resistant (MDR) TB cases in developed countries (mainly because of the human immunodeficiency virus epidemic) in the early nineties that sufficient attention was again focussed on the problem of drug-resistant TB. Drugresistant tuberculosis, and more in particular MDR TB, posed a serious threat to global TB control programmes. Despite this renewed interest, childhood drug-resistant TB remained neglected. The incidence of drug-resistant TB among children, which could give a good indication of currently circulating strains in a community, is hardly known. The management of childhood contacts of adults with infectious MDR TB or children with MDR TB has also not been studied prospectively. All confirmed childhood TB cases from a specific geographic drainage area over a 3.5-year period were prospectively included in a drug resistance surveillance study. The incidence of drug resistance in children was comparable to the incidence of initial (primary plus undisclosed previous treatment) drug resistance documented in adults in the same area. The findings show that the incidence of drug-resistant TB in children in the Western Cape province is low, and probably reflects the level of primary drug resistance amongst organisms currently circulating in this community. The short- and long-term outcome of children <5 years of age in contact with infectious adult MDR TB cases was determined by prospective follow-up for 30 months. The initial evaluation showed an infection rate significantly higher in MDR TB contacts compared with contacts of drug susceptible cases, but the disease rate was lower. On follow-up, many more children became infected or developed disease. The finding that 90% of those who developed disease did so within the first 12 months, indicates that follow-up beyond 12 months is probably not cost-effective in resource poor countries. The results demonstrate that MDR TB is not less infectious than drug susceptible TB. Despite the fact that some children received chemoprophylaxis, 24% of the children eventually developed disease. This is not different from the expected prevalence of disease in childhood contacts <5 years of age of infectious drug-susceptible adult pulmonary TB cases. Restriction fragment length polymorphism analysis confirmed transmission from an adult source case to a child contact in 5 of 6 adult-child pairs in whom both isolates were available. If therefore an isolate of M tuberculosis for susceptibility testing cannot be obtained from a child in close contact with an infectious MDR TB case, the child should therefore be treated according to the drug susceptibility pattern of the source case's strain. Treatment of children with confirmed and probable MDR TB included 2 or 3 drugs to which the adult source case's isolate was susceptible in addition to pyrazinamide and high-dose INH. Duration of treatment ranged from 6 to 12 months depending on the severity of the disease. INH was included in the treatment regimen because low-level resistance to INH was present in about half the cases of primary INH resistance. The pharmacokinetics of INH in children confirmed that an adequate concentration and exposure time could be achieved for this purpose. Ethionamide often caused gastrointestinal adverse events, but these could be overcome in most cases by temporary dose adjustments. The fluoroquinolones, which are not generally recommended for use in children, possibly caused arthralgia in 1 of the17 children treated for ~6 months. This is in accordance with previous reports of the safety of these drugs in children for short- and medium-term treatment. TB disease occurred significantly less often in children who received appropriate chemoprophylaxis (according to the drug susceptibility pattern of the adult source case's isolate). Although this was not a randomised controlled trial, the group that received chemoprophylaxis was at higher risk for developing disease. This implies that prevention of TB in MDR contacts is possible. A prospective, randomised controlled study is necessary to evaluate the best drug combinations and the optimal duration of such chemoprophylactic regimens. / AFRIKAANSE OPSOMMING: Middelweerstandigheid het na vore gekom kort nadat antituberkulose behandeling vir die eerste keer in gebruik geneem is. Die gekombineerde gebruik van middels het klaarblyklik die probleem oorkom. Diere eksperimente wat getoon het dat isoniasied (INH)-weerstandige stamme van Mycobacterium tuberculosis minder infektief en patogenies IS as vatbare stamme, het verdere gerustelling gegee dat middelweerstandigheid nie 'n groot probleem is nie. Die oordrag van INH- en multi-middelweerstandige stamme het egter wel plaasgevind. Studies in kinders, wat hoofsaaklik primêre middelweerstandige tuberkulose (TB) ontwikkel, het getoon dat middelweerstandigheid in volwassenes gevolg is deur 'n soortgelyke toename in middelweerstandige TB in kinders en dat die voorkoms van tuberkuleuse infeksie in kinderkontakte van INH-weerstandige en middelvatbare volwasse TB gevalle dieselfde is. Dis egter eers toe daar 'n beduidende toename in die insidensie van TB en groot uitbrake van multimiddelweerstandige (MDR) TB gevalle in die ontwikkelde lande (hoofsaaklik as gevolg van die menslike immuungebrek virus epidemie) in die vroeë negentigerjare was dat daar opnuut aandag aan die probleem van weerstandige TB geskenk is. Middelweerstandige TB, en in besonder MDR TB, hou 'n ernstige bedreiging vir globale TB beheerprogramme in. Tenspyte van die nuwe belangstelling in middelweerstandige TB is die probleem in kinders steeds afgeskeep. Die insidensie van weerstandige TB in kinders is onbekend alhoewel dit 'n goeie weergawe van die huidig sirkuIerende stamme in 'n gemeenskap sou gee. Die hantering van kinderkontakte van volwassenes met infektiewe MDR TB of kinders met MDR TB is ook nog nie prospektiefbestudeer nie. Alle bevestigde kinder-TB gevalle van 'n spesifieke geografiese gebied is oor 'n 3.5 jaar tydperk prospektief in 'n middelweerstandige waarnemingstudie ingesluit. Die insidensie van middelweerstandigheid in kinders was vergelykbaar met die insidensie van inisiële (primêre weerstandigheid plus onbekende vonge behandeling) middelweerstandigheid in volwassenes van dieselfde gebied. Die bevindinge toon dat die insidensie van middelweerstandige TB in kinders in die Weskaap provinsie laag is. Dit weerspieël waarskynlik die vlak van primêre middelweerstandigheid in organismes wat tans in hierdie gemeenskap sirkuleer. Die kort- en langtermyn uitkoms van kinders <5 jaar oud wat in kontak met infektiewe volwasse MDR TB gevalle was, is prospektief tydens 'n 30-maande opvolg bepaal. Die aanvanklike evaluasie het 'n beduidend hoër infeksiekoers in die MDR TB kontakte in vergelyking met kontakte van middelvatbare gevalle getoon, maar die siektekoers was laer. Tydens die opvolgperiode het baie meer kinders infeksie of siekte ontwikkel. Aangesien 90% van dié wat siekte ontwikkel het, dit gekry het binne die eerste 12 maande, is opvolg ná 12 maande waarskynlik nie koste-effektief in hulpbronbeperkte lande nie. Die bevindinge toon dat MDR TB nie minder infektief is as middelvatbare TB nie. Tenspyte daarvan dat sommige kinders chemoprofilakse ontvang het, het 24% van die kinders uiteindelik siekte ontwikkel. Dit verskil nie van die verwagte siekte-insidensie van kinderkontakte <5 jaar oud wat in kontak met infektiewe volwasse middelvatbare pulmonale TB was nie. Restriksie fragment lengte polimorfisme analise het oordrag van volwasse brongeval na kinderkontak in 5 uit 6 volwasse-kind pare, van wie beide isolate beskikbaar was, bevestig. Indien daar dus nie 'n isolaat van M. tuberculosis vir vatbaarheidstoetse van 'n kind met nabye kontak met 'n infektiewe MDR TB geval beskikbaar is nie, behoort die kind volgens die middelvatbaarheidspatroon van die brongeval se stam behandel te word. Behandeling van kinders met bevestigde of waarskynlike MDR TB het 2 tot 3 middels waarvoor die volwasse brongeval se isolaat vatbaar was, ingesluit, tesame met pirasinamied en hoë-dosis INH. Die duur van behandeling het gewissel van 6 tot 12 maande op grond van die omvang van die siekte. INH is in die behandeling ingesluit omdat dit getoon is dat ongeveer die helfte van die gevalle met primêre INHweerstandigheid lae-vlak weerstandigheid het. Die farmakokinetika van INH in kinders het bevestig dat genoegsame vlakke en blootstellingstyd aan INH vir hierdie doel bereik kan word. Etionamied het dikwels gastrointestinale newe-effekte veroorsaak, maar dit kon in die meeste gevalle oorkom word. Die fluorokwinolone, wat nie oor die algemeen in kinders aanbeveel word nie, het moontlik artralgie veroorsaak in 1 uit 17 kinders wat vir ~6 maande behandel is, wat vorige verslae oor die veiligheid van hierdie middels in kort- en medium-termyn behandeling bevestig. TB-siekte het beduidend minder dikwels voorgekom in kinders wat toepaslike chemoprofilakse (volgens die middelvatbaarheidspatroon van die volwasse brongeval se isolaat) ontvang het. Alhoewel dit nie 'n ewekansig gekontroleerde studie was nie, het die groep wat chemoprofilakse ontvang het die hoogste risiko vir die ontwikkeling van siekte gehad. Dit dui daarop dat voorkoming van TB in MDR TB kontakte moonlik is. 'n Prospektiewe, ewekansig gekontrolleerde studie is nodig om die beste middel kombinasies en die optimale duur van so 'n chemoprofilaktiese behandeling te bepaal.

O presente trabalho desenvolve um modelo matemático multicompartimental, representado por um sistema de equações diferenciais ordinárias, da dinâmica epidemiológica da tuberculose. Modela-se, além do comportamento natural da doença, o tratamento de casos infectantes, enquanto medida de controle. Este último aspecto da modelagem leva em conta a duração do tratamento e a possibilidade de não adesão. Entre as premissas do modelo, destacam-se a ausência de resistência do bacilo ao esquema terapêutico, a mesma probabilidade de entrada em tratamento de casos já tratados anteriormente e casos novos e a ausência de circulação do HIV. Utilizou-se dados publicados na literatura para a estimativa dos parâmetros. A simulação da introdução da doença em uma população de suscetíveis leva ao equilíbrio, não tendo sido reproduzido o comportamento de queda duradoura da morbidade, observada em várias regiões do mundo. A simulação do tratamento dos casos infectantes produz uma redução acelerada da morbidade nos primeiros anos após o que, dependendo da taxa de entrada em tratamento, pode levar tanto a um novo equilíbrio, como produzir uma queda lenta, porém constante da morbidade tuberculosa, com tendência à extinção. O abandono do tratamento reduz a sua efetividade epidemiológica, mas na maioria das situações simuladas não anula completamente o impacto desta atividade de controle, mesmo no caso de taxas de abandono muito elevadas. É possível produzir soluções em que o abandono do tratamento leve a um prejuízo epidemiológico em relação ao comportamento da doença na ausência de intervenção, alterando-se parâmetros. O modelo proposto é apenas uma etapa na modelagem da dinâmica de transmissão da tuberculose na ausência de intervenção, se prestando, no entanto, enquanto instrumento lógico para simulações da efetividade de programas de controle. / This study develops a mathematical model for the dynamics of tuberculosis, as a system of ordinary differential equations, The model includes the treatment of infectious cases as a control measure, allowing for simulation of non compliance, besides the natural behavior of the disease. The most important model\'s assumptions are bacilary sensibility to drugs, absence of HIV circulation, and treatment of new and old cases at the same rate. The parameters were estimated from data published in the medicai literatura. The simulation of the introduction of disease in a susceptible population leads to growing morbidity followed by an equilibrium point. The model did not reproduce the decreasing mortality observed in many countries before drugs were available. The simulation of the infectious cases treatment results in a rapid decrease of morbidity in the first few years, followed by a new steady state ar by a constant decrease at lower rate. The non compliance to the treatment reduce its effectivity as a contrai measure. Depending on certain parameters values, the non compliance may lead to an equilibrium point with higher morbidity than in the absence of any contrai measure, but in most of the simulations there was remaining treatment effectivity even with very high non compliance ratas. This model may be considered only a step in the work of modeling the natural tuberculosis dynamics, but it is already an important tool for the simulation of the effectivity of the control programmes.

Este trabalho apresenta o resultado do estudo das causas que interferem na busca passiva de casos de tuberculose pulmonar na população. Entrevistaram-se 350 indivíduos, bacilíferos e não bacilíferos, que procuraram o Centro de Saúde de Pinheiros-SP, durante o ano de 1985. Foram estudadas as informações obtidas referentes ao tempo decorrido desde a percepção de alguma sintomatologia pela população de estudo até a sua chegada ao Centro de Saúde. Os resultados obtidos permitem supor que boa parte da responsabilidade pela demora no atendimento correto da população pode ser atribuída aos profissionais das instâncias anteriores à procura do Centro de Saúde. Outros fatores relacionados à àrea do comportamento humano e a aspectos sócio-econômicos foram identificados como causa provável de demora para a procura de assistência adequada à saúde. Concluiu-se que a população não conhece ou conhece pouco as características da função assistencial do centro de saúde, com exceção da gratuidade dos serviços oferecidos. Este conjunto de fatores resultou num tempo de sintomatologia que variou de menos de 3 semanas até mais de 24 meses, com maior concentração de casos no espaço de tempo compreendido entre 3 semanas ate 12 meses, significando maior risco de disseminação da infecção na comunidade. / This work presents the results of the study of causes that interfere with the passive search of pulmonary tuberculosis cases in the population. Three hundred and fifty infection spreading and non infection spreading subjects who looked up the Pinheiros Public Health Center in the city of São Paulo throughout 1985 were interviewed. Information obtained regarding intervening time between perception of any symptom by the study population and its arrival at the Health Center was studied. The results obtained point ot to the fact that a good deal of responsability for the delay in the provision of correct care lies with the professionals of the anterior instances attended by the population before looking up the Health Center. Other factors related to the area of human behaviour and socio-economic aspects were also identified as probable causes of the delay in obtaining adequate health care. It is concluded that the population has little or no knowledge whatsoever regarding the health care function of the Health Center, save it being free of charge. This group of factors resulted in a symptomatology time span that varied from less than three weeks to twenty-four months with a higher concentration rate comprised between three weeks and twelve months meaning a larger infection spreading risk in the community.

O presente trabalho desenvolve um modelo matemático multicompartimental, representado por um sistema de equações diferenciais ordinárias, da dinâmica epidemiológica da tuberculose. Modela-se, além do comportamento natural da doença, o tratamento de casos infectantes, enquanto medida de controle. Este último aspecto da modelagem leva em conta a duração do tratamento e a possibilidade de não adesão. Entre as premissas do modelo, destacam-se a ausência de resistência do bacilo ao esquema terapêutico, a mesma probabilidade de entrada em tratamento de casos já tratados anteriormente e casos novos e a ausência de circulação do HIV. Utilizou-se dados publicados na literatura para a estimativa dos parâmetros. A simulação da introdução da doença em uma população de suscetíveis leva ao equilíbrio, não tendo sido reproduzido o comportamento de queda duradoura da morbidade, observada em várias regiões do mundo. A simulação do tratamento dos casos infectantes produz uma redução acelerada da morbidade nos primeiros anos após o que, dependendo da taxa de entrada em tratamento, pode levar tanto a um novo equilíbrio, como produzir uma queda lenta, porém constante da morbidade tuberculosa, com tendência à extinção. O abandono do tratamento reduz a sua efetividade epidemiológica, mas na maioria das situações simuladas não anula completamente o impacto desta atividade de controle, mesmo no caso de taxas de abandono muito elevadas. É possível produzir soluções em que o abandono do tratamento leve a um prejuízo epidemiológico em relação ao comportamento da doença na ausência de intervenção, alterando-se parâmetros. O modelo proposto é apenas uma etapa na modelagem da dinâmica de transmissão da tuberculose na ausência de intervenção, se prestando, no entanto, enquanto instrumento lógico para simulações da efetividade de programas de controle. / This study develops a mathematical model for the dynamics of tuberculosis, as a system of ordinary differential equations, The model includes the treatment of infectious cases as a control measure, allowing for simulation of non compliance, besides the natural behavior of the disease. The most important model\'s assumptions are bacilary sensibility to drugs, absence of HIV circulation, and treatment of new and old cases at the same rate. The parameters were estimated from data published in the medicai literatura. The simulation of the introduction of disease in a susceptible population leads to growing morbidity followed by an equilibrium point. The model did not reproduce the decreasing mortality observed in many countries before drugs were available. The simulation of the infectious cases treatment results in a rapid decrease of morbidity in the first few years, followed by a new steady state ar by a constant decrease at lower rate. The non compliance to the treatment reduce its effectivity as a contrai measure. Depending on certain parameters values, the non compliance may lead to an equilibrium point with higher morbidity than in the absence of any contrai measure, but in most of the simulations there was remaining treatment effectivity even with very high non compliance ratas. This model may be considered only a step in the work of modeling the natural tuberculosis dynamics, but it is already an important tool for the simulation of the effectivity of the control programmes.

Tuberculosis is a disease of global importance and remains the leading cause of death in the developing world. In South Africa a weak notification system and poor occupational health services for health care workers has resulted in little information being available about the incidence of tuberculosis and the groups at highest risk of contracting tuberculosis amongst health care workers, the clinical presentation and management of workers infected with tuberculosis. The purpose of this study was to describe the incidence of tuberculosis, and the clinical and public health aspects of the management of tuberculosis among health care workers in eight public sector hospitals in the Ethekwini Municipality of KwaZulu-Natal. Data was collected through a retrospective review of hospital records for the study period January 1999 to June 2004. Study findings: Five hundred and eighty three (N=583) health care workers were diagnosed with tuberculosis for the period under review. The mean age of the HCWs was 38 years (95% Cl: 37-39). The mean cumulative incidence for the study period was 1040/100 000 HCW population (95% Cl: 838-1242). The mean cumulative incidence of TB was highest in males (1544/100 000 HCW population; 95% Cl 1228 -1859), the age group 25 to 34 years (1043/100 000 HCW population; 95% CI: 650 -1436) and in paramedical staff (1675/100 000 HCW population; 95%CI: 880-2470). The majority of health care workers presented with pulmonary tuberculosis (77%, n=322) and 3% (n=13) had multidrug resistant tuberculosis. Successful treatment outcomes were achieved in 63% (n=334) of health care workers. Only one hospital has a work place policy with regard tuberculosis in health care workers. Compensation for this occupational disease was sought as follows. Submissions of a first medical report were made in 107 (18%) of the 583 health care workers. In the 107 cases initially reported submission of progress reports (n=75; 70%) and final reports (n=60; 56%) decreased considerably. In conclusion, the incidence of tuberculosis in health care workers has increased annually since 1999 and the treatment outcomes among health care workers do not reach the targets set by the National Tuberculosis Control Programme. Recommendations based on the study findings include establishing a uniform provincial policy for the prevention and reduction of tuberculosis infections among health care workers for implementation in hospitals; the implementation of a medical surveillance system for health care workers with respect to tuberculosis and a provincial training programme for staff on the clinical and administrative management of TB in health care workers. / Thesis (M.Med.)-University of KwaZulu-Natal, 2006.