Clinical implication of novel drug resistance-conferring mutations in resistant tuberculosis.

Evolving novel and/or unfamiliar mutations are revolutionizing the pathways of antibiotic resistance of clinical tuberculosis. The accumulation and interaction of these poorly characterized mutations augment the complexity of resistant pathogenic strains and raise public health concerns. This article reviews our current understanding of the genetic changes that characterize drug resistance in tuberculosis and highlights the imperative for further investigations focusing on the effects of an individual mutation and interacting mutations with detailed strain epidemiology, particularly as these pertain to technology-limited countries with high tuberculosis incidence rates. Concomitantly, there is a need for the development, testing, and uptake of new tools for studying the effects of these mutations in drug resistance and fitness cost of the pathogen. Such genetic data are critical for effective localized and global tuberculosis control interventions and for accurate epidemiological predictions.

Knowledge, awareness and use of HIV services among the youth from nomadic and agricultural communities in Tanzania.

BACKGROUND: Nomadic life not only prevents the community from accessing and utilising HIV services but also deters them from obtaining reliable information on HIV. METHODS: We conducted a cross-sectional study of youth aged 10-24 years from the Kilindi and Ngorongoro Districts in Tanzania to assess knowledge, accessibility and utilisation of HIV/AIDS services among nomadic and agricultural youths. RESULTS: Of 518 youths interviewed, 279 (53.9%) were males, and 276 (53.3%) were from agricultural communities. A significant proportion of youths from agricultural communities had correct knowledge of AIDS (n = 126, 45.8%; P = 0.002), HIV transmission (n = 273, 98.9%; P = 0.001) and comprehensive knowledge of HIV/AIDS (n = 78, 28.5%; P = 0.009) compared to nomads. Youths from agricultural communities were two times (OR 1.8, 95% CI 1.2-2.6) more likely to be aware of the availability of formal HIV services. Awareness of the availability of HIV services was higher among married individuals than in unmarried ones (OR 3.8, 95% CI 2.0-7.4), and significantly higher among youths with secondary/college education than in those who did not have formal education (OR 5.3, 95% CI 2.3-12.4). The uptake of HIV services was lower among nomadic youths. CONCLUSION: Knowledge, awareness and utilisation of HIV/AIDS transmission services were low in general, and even lower among nomadic youths, calling for more targeted interventions.

CONTEXTE: La vie nomade n'entrave pas seulement l'accès et l'utilisation des services VIH par une communauté mais empêche également l'accès à une information VIH fiable. MÉTHODES: Nous avons réalisé une étude transversale auprès de jeunes de 10­24 ans des districts de Kilindi et de Ngorongoro en Tanzanie pour évaluer les connaissances, l'accessibilité et l'utilisation des services VIH/SIDA parmi les jeunes nomades et agriculteurs. RÉSULTATS: Sur 518 jeunes, 279 (53,9%) étaient des garçons, 276 (53,3%) venaient de communautés agricoles. Une proportion significative des jeunes de communautés agricoles avaient des connaissances correctes en matière de SIDA (n = 126 ; 45,8% ; P = 0,002), de transmission du VIH (n = 273 ; 98,9% ; P = 0,001) de connaissances complètes du VIH/SIDA (n = 78 ; 28,5% ; P = 0,009) comparées à celles des nomades. Les jeunes des communautés agricoles étaient deux fois plus au courant (OR 1,8 ; IC 95% 1,2­2,6) de la disponibilité de services VIH formels. La connaissance de la disponibilité de services VIH était plus élevée chez les jeunes mariés (OR 3,8 ; IC 95% 2,0­7,4) comparés aux célibataires, et significativement plus élevée parmi les jeunes ayant eu une instruction secondaire/supérieure comparés à ceux qui n'avaient eu aucune éducation formelle (OR 5,3 ; IC 95% 2,3­12,4). L'utilisation des services VIH était plus faible parmi les nomades. CONCLUSION: Les connaissances, la sensibilisation et l'utilisation des services de transmission du VIH/SIDA étaient bas et encore plus bas chez les jeunes nomades, appelant des interventions plus ciblées.

Xpert® MTB/RIF assay testing on stool for the diagnosis of paediatric pulmonary TB in Tanzania.

SETTING: Six health facilities in Dar es Salaam, Tanzania. OBJECTIVE: To evaluate the use of stool specimens in the diagnostic workup of paediatric TB using the Xpert® MTB/RIF assay. DESIGN: Between December 2018 and May 2019, we performed a cross-sectional diagnostic study of children aged between 1 month and 14 years with presumptive TB. A single stool specimen was tested using Xpert. The result was compared with the reference microbiological standard for respiratory or gastric specimens tested using Xpert and/or solid culture. The sensitivity, specificity and predictive values of stool Xpert assay were assessed. RESULTS: A total of 225 children with a median age of 2.17 years (IQR 1.16-5.19) were enrolled; 165/225 (73.3%) were aged <5 years. Of 225 children, 8 (3.6%) were diagnosed with TB as they were culture- or Xpert-positive on sputum/gastric aspirate. The stool Xpert assay showed a sensitivity of 62.5% (95% CI 25-92) and specificity of 100% (95% CI 98-100) against the reference standard. CONCLUSION: Use of the Xpert assay on stool specimens had a moderate sensitivity and high specificity in the diagnosis of pulmonary TB in children. Our data adds to the body of evidence for the use of Xpert assay on stool as a non-respiratory specimen to complement conventional methods used to diagnose the disease.

CONTEXTE: Six structures de santé à Dar es Salaam, Tanzanie. OBJECTIF: Evaluer l'utilisation d'échantillons de selles dans le bilan diagnostique de la TB pédiatrique en utilisant le test Xpert® MTB/RIF. SCHÉMA: Entre décembre 2018 et mai 2019, nous avons réalisé une étude transversale de bilans d'enfants âgés d'un mois à 14 ans avec la TB présumée. Un échantillon unique de selles a été testé par l'Xpert. Le résultat a été comparé avec comme référence le standard microbiologique d'échantillons respiratoires ou gastriques testés par test Xpert et/ou culture solide. La sensibilité, la spécificité et les valeurs prédictives de l'Xpert sur les selles ont été évaluées. RÉSULTATS: Ont été enrôlés 225 enfants d'âge médiane 2,17 ans (IQR 1,16­5,19) dont 165 (73,3%) avaient moins de cinq ans. Huit (3,6%) enfants ont eu un diagnostic de TB par culture ou test Xpert positif sur aspiration de crachats/gastrique. Le test Xpert sur les selles a montré une sensibilité de 62,5% (IQR 25­92) et une spécificité de 100% (IQR 98­100) vis-à-vis du standard de référence. CONCLUSION: Le recours au test Xpert sur des échantillons de selles a montré une sensibilité modérée et une spécificité élevée dans le diagnostic de la TB pulmonaire des enfants. Nous données confirment l'intérêt de l'utilisation du test Xpert sur les selles comme échantillon non respiratoire pour compléter les méthodes conventionnelles de diagnostic de la maladie.

Patient's dissatisfaction with the public and private laboratory services in conducting HIV related testing in Tanzania.

BACKGROUND: Patient's satisfaction with both private and public laboratory services is important for the improvement of the health care delivery in any country. METHODS: A cross-sectional survey was conducted in 24 randomly selected health facilities with laboratories that are conducting HIV related testing, in Mainland Tanzania. The study assessed patient's satisfaction with the laboratory services where by a total of 295 patients were interviewed. RESULTS: Of data analyzed for a varying totals from 224 to 294 patients, the percentage of dissatisfaction with both public and private laboratory services, ranged from 4.3% to 34.8%, with most of variables being more than 15%. Patients who sought private laboratory services were less dissatisfied with the cleanness (3/72, 4.2%) and the privacy (10/72, 13.9%) than those sought public laboratory service for the same services of cleanness (41/222, 18.5%) and privacy (61/222, 27.5%), and proportional differences were statistically significant (X2 = 8.7, p = 0.003 and X2 = 5.5, p = 0.01, respectively). Patients with higher education were more likely to be dissatisfied with privacy (OR = 1.8, 95% CI: 1.1-3.1) and waiting time (OR = 2.5, 95% CI: 1.5 - 4.2) in both private and public facilities. Patients with secondary education were more likely to be dissatisfied with the waiting time (OR = 5.2; 95%CI: 2.2-12.2) and result notification (OR = 5.1 95%CI (2.2-12.2) than those with lower education. CONCLUSION: About 15.0% to 34.8% of patients were not satisfied with waiting time, privacy, results notification cleanness and timely instructions. Patients visited private facilities were less dissatisfied with cleanness and privacy of laboratory services than those visited public facilities. Patients with higher education were more likely to be dissatisfied with privacy and waiting time in both private and public facilities.

Dissatisfaction with the laboratory services in conducting HIV related testing among public and private medical personnel in Tanzania.

BACKGROUND: A comprehensive care and treatment program requires a well functioning laboratory services. We assessed satisfaction of medical personnel to the laboratory services to guide process of quality improvement of the services. METHODOLOGY: A cross-sectional survey in 24 randomly selected health facilities in Mainland Tanzania was conducted to assess the satisfaction of the medical personnel with the laboratory services. RESULTS: Of 235 medical personnel interviewed, 196 were valid for analysis and about one quarter were dissatisfied with the laboratory services. Personnel dissatisfied with the services were 38.3% in timely test result, 24.5% in correct and accurate results and 22.4% in clear complete results. The personnel in public laboratories were more dissatisfied with timely test results (OR = 3.6, 95% CI 1.8, 7.3), correct results (OR = 4.1, 95% CI 1.6, 10.8) and clear complete results (OR = 5.0 95% CI 1.6, 15.2). Personnel dissatisfied with the services in 15 laboratories sending specimens to referral laboratories, varied from 13% in availability of equipment to 57% in timely results feedback from the referral laboratories. Personnel dissatisfied with the services in 14 referral laboratories, varied from 28.6% in properly identified specimen to 42.9% in clear, accurate test request and communication. CONCLUSION: About one quarter of medical personnel in sending or receiving laboratories were dissatisfied with the services. Comparing the personnel in public and private, the personnel in public laboratories were 4 times more dissatisfied with the timely test and correct results; and 5 times more dissatisfied with clear and complete test results.

Population impact of factors associated with prevalent pulmonary tuberculosis in Tanzania.

SETTING: Tanzania has an estimated tuberculosis (TB) prevalence of 295 per 100 000 adult population. There is currently no nationally representative information on factors associated with TB in Tanzania. OBJECTIVE: To determine the demographic and clinical factors associated with bacteriologically confirmed TB in the adult general population of Tanzania. DESIGN: A case-control study nested in a nationally representative TB prevalence survey. All patients with bacteriologically confirmed pulmonary TB (PTB) constituted cases and a representative sample of people without bacteriologically confirmed PTB constituted controls. We calculated adjusted odds ratios (aORs) to identify factors associated with TB. RESULTS: Age groups 25-34 years (aOR 3.7, 95%CI 1.5-8.8) and 55-64 years (aOR 2.5, 95%CI 1.1-5.5), male sex (aOR 1.6, 95%CI 1.1-2.3) and low body mass index (BMI) (aOR 1.7, 95%CI 1.1-2.8) were significantly associated with TB. Association with human immunodeficiency virus (HIV) and diabetes mellitus (DM) was not statistically significant. The population attributable fraction (PAF) was 2% (95%CI -2 to 5) for DM and 3% (95%CI -2 to 8) for HIV. CONCLUSION: Being in an older age group, being male and having a low BMI were associated with bacteriologically confirmed PTB. On the population level, classic risk factors for TB have no major effect on prevalent TB from which future transmission may occur.

Patient knowledge, practices and challenges to health care system in early diagnosis of mycobacterial adenitis.

OBJECTIVE: To assess diagnostic delay, knowledge and practices related to tuberculosis among patients with mycobacterial adenitis. DESIGN: A cross sectional study involving comparison analysis of high-risk groups. SETTING: Seven hospitals in rural and semi-rural districts of Arusha. SUBJECTS: Four hundred and twenty six clinically diagnosed adenitis patients. INTERVENTIONS: Biopsy specimens were processed for culture, histology, and sera for HIV testing. A questionnaire was used to assess knowledge, practice, and diagnostic time. MAIN OUTCOME MEASURES: Tribal comparisons were made using proportions and means. RESULTS: About 90% (387/423) of patients first visited medical facilities within a mean time of 10.1(SD, 15.7) weeks after becoming aware of their illness, and a diagnosis was made at a mean of 27 (SD, 25) weeks. Non-Iraqw patients, especially the Datoga, practised drinking raw milk (35.2% 43/122), eating raw animal products (18.8% 24/128) and living in houses with poor ventilation (33.6% 44/131), more than Iraqw patients. Of the investigations done, 14.5% (60/415) were culture positive, 11.3% (16/142) were HIV positive, and 73.6% (128/174) had histological features consistent with tuberculosis. The knowledge of TB spread by air droplets was poorer in Iraqw (74.1%, 203/274) than in non-lraqw (61.1%, 77/126) patients. About 35.0% (45/129) of non-lraqw and 27.3% (79/289) of Iraqw patients were not aware that TB could be transmitted from animals to humans. CONCLUSIONS: The health system diagnostic delay is about twice the patient delay. The knowledge and practices related to both human and bovine TB transmission were poor in all patients, especially in the patients from nomadic tribes.

Health care-seeking behaviour among people with cough in Tanzania: findings from a tuberculosis prevalence survey.

SETTING: The study was conducted within a nation-wide population-based tuberculosis (TB) prevalence survey in the adult population in Tanzania. OBJECTIVE: To assess the health care-seeking behaviour of coughers presumed to have TB. DESIGN: A survey in which participants were screened for TB using a symptom questionnaire and chest X-ray (CXR). Those with cough of ⩾ 2 weeks and/or who were coughing blood were interviewed about their health care-seeking behaviour and socio-demographic and clinical factors. RESULTS: Of 3388 people with presumptive TB, 31.0% (1051/3388) had sought treatment for their symptoms. Of these, about 42% (445/1051) sought care at sites with TB diagnostic capacity, where sputum examination was performed in 37.1% (165/445) and CXR in 28.1% (125/445). In sites with limited TB diagnostic capacity, fewer than 1% were referred for sputum examination or CXR. Individuals with additional symptoms were more likely to seek treatment. Knowledge about TB was significantly associated with care seeking at sites with TB diagnostic capacity. CONCLUSIONS: A third of the persons with cough symptoms consistent with TB had sought health care. About 42% sought care in sites with TB diagnostic capacity, but most did not undergo TB diagnostic procedures, precluding a timely diagnosis.

Tribal differences in perception of tuberculosis: a possible role in tuberculosis control in Arusha, Tanzania.

SETTING: Arusha, Tanzania. OBJECTIVE: To determine tribal differences in knowledge and practices that might influence tuberculosis control. METHOD: Twenty-seven villages were selected randomly out of 242 villages in four districts. In each village, a general and a livestock keeping group were selected at random. The households were home-visited and 426 family members were interviewed. RESULTS: On average, 40% of respondents practised habits that might expose them to both bovine and human tuberculosis. The Barabaig tribe had a significantly higher number of respondents (50%, chi2(2) = 5.1, P = 0.024) who did not boil milk. Eating uncooked meat or meat products was practised by 17.9% of all respondents. The habit was practised more by Iraqw (21.1%, chi2(2) = 6.9, P = 0.008) and Barabaig (31.6%, chi2(2) = 5.6, P = 0.016) than other tribes. About 75% of the respondents had a poor knowledge of tuberculosis. CONCLUSION: All tribes had habits and beliefs that might expose them to both bovine and human tuberculosis. The Iraqw and Barabaig tribes practised such habits more than other tribes. Knowledge of tuberculosis was limited in all tribes.

The role of livestock keeping in tuberculosis trends in Arusha, Tanzania.

SETTING: Arusha, Tanzania. OBJECTIVE: To assess risk factors that might influence TB control in the general population and in livestock-keepers. METHODS: Of 242 villages in four districts, 27 were selected randomly. In each village, a general and a livestock-keeping group were selected at random. The households were home-visited and 426 family members were interviewed. RESULTS: On average, three-quarters of households practised at least one risk activity for transmission of zoonotic tuberculosis, and respondents had poor knowledge about tuberculosis. In the livestock-keeping group, the risks of having a tuberculosis patient in the family were determined by poor ventilation (OR 2.6, 95% CI 1.1-6.5), confining livestock indoors with people (OR 2.3, 95%CI 1.1-5.0) and multiple determinants including poor ventilation (OR 13.5, 95% CI 2.5-71.7). Risk activities and the risks of having a tuberculosis patient in a family were significantly higher in the livestock-keeping group. CONCLUSIONS: The respondents had limited knowledge about tuberculosis, and the households had practices that posed potential risks for both human and bovine tuberculosis infection. Poor ventilation and confining livestock indoors were associated with tuberculosis spread in the households. These risks were observed more in the livestock-keeping group than in the general population group.

Trend in HIV prevalence among tuberculosis patients in Tanzania, 1991-1998.

OBJECTIVE: To determine the trend in human immunodeficiency virus (HIV) prevalence among tuberculosis patients in Tanzania and estimate what proportion of the increase in notification rates between the surveys was directly attributable to HIV infection. METHODS: Consecutive tuberculosis patients were enrolled over 6-month periods in most regions. Demographic and clinical data were collected on standard forms and a single HIV ELISA test performed. Trends in tuberculosis incidence were estimated from regional notification data. RESULTS: Of 10612 eligible tuberculosis patients, 44% had HIV infection, compared with 32% in the previous survey. The largest increase was observed in the youngest birth cohorts, suggesting active HIV transmission. Approximately 60% of the increase in notification rates of smear-positive tuberculosis between surveys was directly attributable to HIV infection. CONCLUSION: The HIV epidemic has had a strong influence on tuberculosis incidence. However, since 1995, tuberculosis notification data have increased less steeply, AIDS notifications have gone down, and HIV prevalence in blood donors has not increased a great deal. Another survey among tuberculosis patients in 5 years' time may show whether the HIV epidemic in Tanzania has reached a maximum or steady state.

Mycobacterial adenitis: role of Mycobacterium bovis, non-tuberculous mycobacteria, HIV infection, and risk factors in Arusha, Tanzania.

OBJECTIVE: To assess risk factors and mycobacterial agents in mycobacterial adenitis. DESIGN: Cross sectional involving comparison analysis of high-risk groups. SETTING: Seven hospitals in rural and semi-rural districts of Arusha. SUBJECTS: The study comprised of 457 patients of clinically diagnosed mycobacterial adenitis. INTERVENTIONS: Biopsy materials were cultured and identification of mycobacterial isolates, and HIV infection testing were performed using standard methods. A questionnaire was used to establish information for assessing risk factors. MAIN OUTCOME MEASURES: Proportions of mycobacterial isolates, risk factors and odds ratios. RESULTS: Of the 457 specimens, 65(14.2%) were culture positive. Isolates identified were M. bovis, 7(10.8%) M. tuberculosis, 27(41.5%) and non-tuberculous mycobacteria 31(47.7%). HIV infection and ingestion of raw milk were linked with increased risk of M. bovis infection by OR of 13.6 (95% CI, 1.7 - 109.9) and 15.28 (3.26 - 71.7), respectively. On multivariate analysis, an OR of 16.2 (1.3 - 201.3) for having M. bovis adenitis was linked to HIV infection, raw milk and houses with poor ventilation. An OR of 5.2 (1.2 - 20.6) for non-tuberculous mycobacterial adenitis was linked to history of TB in the family, HIV infection, raw milk, raw animal products and poor knowledge on transmission of tuberculosis. CONCLUSIONS: M. bovis caused one out of ten cases of culture positive mycobacterial adenitis. Non-tuberculous mycobacteria were more common than M. tuberculosis (50% and 40% of the cases, respectively). HIV infection and raw animal products are among the risk factors identified for M. bovis and non-tuberculous mycobacterial adenitis.

National anti-tuberculosis drug resistance study in Tanzania.

OBJECTIVE: To assess the prevalence of anti-tuberculosis drug resistance in a national representative sample of tuberculosis (TB) patients in Tanzania according to recommended methodology. DESIGN: Cluster survey, with 40 clusters sampled proportional to size, of notified TB patients from all diagnostic centres in the country. RESULTS: The survey enrolled 1019 new and 148 retreatment patients. The adjusted prevalence of Mycobacterium tuberculosis strains resistant to any of the four first-line drugs in new patients was 8.3%, while the prevalence of multidrug-resistant TB (MDR-TB) was 1.1%. In retreatment patients, the crude prevalence for any resistance and for MDR-TB was respectively 20.6% and 3.9%. The prevalence of drug resistance did not differ in relapse patients compared to failure patients. These estimates are among the lowest in those African countries with an estimated level of drug resistance in the last 5 years. CONCLUSION: The low levels of drug resistance in Tanzania are likely due to a well performing TB control programme and the absence of noticeable involvement of the private sector in TB treatment.

How does clinical diagnosis of mycobacterial adenitis correlate with histological findings?

OBJECTIVE: To describe and compare histopathological findings with clinical criteria in diagnosis of TB adenitis. METHODS: Lymph node biopsies were obtained from 213 patients. Specimens were processed for culture and histopathologic examination, using standard methods. One hundred blocks with good preservation of tissue morphology were selected for detailed histological examination. RESULTS: About 75% of 213 patients had granulomas. In the remaining 25%, neither histopathological nor microbiological evidence of mycobacterial disease was found. Of 100 blocks selected for detailed examination, 79 blocks had granulomatous changes. The granulomas were well organised in 24%, mixed in 33%, and poorly organised in 43%. Langhans giant cells and acid-fast bacilli were observed in 88.6% and 21.5% of the 79 blocks, respectively. Cultured specimens were positive in about 10% of 79 biopsy specimens. CONCLUSIONS: Histological evidence of mycobacterial disease was only found in three quarters of patients that were clinically diagnosed and started on empirical treatment for tuberculous adenitis. Neither histological nor mycobacteriological evidence was found in a quarter of the patients who were already on treatment for TB, basing on clinical criteria. These findings call for new research on simple diagnostic tools for patients who seek care for s ymptoms of extra-pulmonary TB.