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.

Prevalence of pulmonary tuberculosis in adult population of Tanzania: a national survey, 2012.

SETTING: Tanzania is classified as one of the 22 high tuberculosis (TB) burden countries; however, the true burden of TB disease in the country remains unknown. OBJECTIVE: To assess the prevalence of bacteriologically confirmed pulmonary TB (PTB) in the adult population. DESIGN: This was a community-based cluster randomised survey with proportional-to-population-size selection of primary sampling units (districts). Participants were screened for TB using a symptom questionnaire and chest X-ray (CXR). Those with abnormal CXR and/or at least one symptom suggestive of TB were classified as individuals with presumptive TB, and asked to submit three sputum specimens for smear microscopy and culture. RESULTS: The weighted prevalence for sputum smear-positive TB cases was 249 per 100 000 adult population (95%CI 192-305) and that for bacteriologically confirmed TB cases was 293/100 000 (95%CI 228-358). Individuals aged ⩾45 years comprised 55% (71/129) of the identified smear-positive cases, but just 28% (6793/24 648) of the notified TB cases. CXR screening identified more TB cases than symptom screening. When weighted for human immunodeficiency virus prevalence among notified new smear-positive cases, the overall case detection of incident TB cases in 2012 was between 37% and 48%. CONCLUSIONS: The prevalence of sputum smear-positive PTB and bacteriologically confirmed PTB in the adult population was higher than previous World Health Organization estimates. There is a potential underestimation of the number of bacteriologically confirmed PTB cases in the adult population. The age distribution of prevalent cases suggests an epidemiological shift towards the older generations, which has been a sign of successful TB control activities in the past. However, the survey shows that many infectious TB cases are currently missed by the National Tuberculosis Programme.

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.

Validation of indirect tuberculosis treatment adherence measures in a resource-constrained setting.

SETTING: Arusha, Mwanza, Mufindi and Kilosa in Tanzania. OBJECTIVE: To assess the test characteristics of three indirect adherence measures against a gold standard of direct measurements of drug intake for use in a resource-constrained setting. METHODS: We assessed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and the diagnostic odds ratio (dORs) of three indirect adherence measurement tools against direct measurement in urine using the IsoScreen assay. RESULTS: The single adherence question of missed doses in the last 2 days had the highest dOR (40.3) compared to the Morisky medication adherence scale (MMAS, 2.5) and pill counts (3.4). The sensitivities of these measures were respectively 97.9%, 92% and 89.6%. Specificity ranged from 46.4% (adherence question) to 17.9% (MMAS). The PPVs of adherence question, pill counts and MMAS were respectively 97.6%, 96.5% and 94.2%, while the NPVs ranged from 50% (adherence question) to 3.1% (MMAS). CONCLUSION: Among several instruments for indirect adherence measure in the routine setting of the Tanzanian National Tuberculosis and Leprosy Programme, a single adherence question was found to have the best discriminatory power. However, the single adherence question might not adequately identify patients who are non-adherent. Confirmatory studies are needed, especially in settings with low adherence rates.

Patient costs during tuberculosis treatment in Bangladesh and Tanzania: the potential of shorter regimens.

OBJECTIVE: To estimate the costs incurred by patients during the intensive and continuation phases of the current 6-month tuberculosis (TB) regimen in Bangladesh and Tanzania, and thus identify potential benefits to patients of a shorter, 4-month treatment regimen. DESIGN: The validated Stop TB patient cost questionnaire was adapted and used in interviews with 190 patients in the continuation phase of treatment with current regimens. RESULTS: In both countries, overall patient costs were lower during 2 months of the continuation phase (US$74 in Tanzania and US$56 in Bangladesh) than during the 2 months of the intensive phase of treatment (US$150 and US$111, respectively). However, continuation phase patient costs still represented 89% and 77% of the 2-month average national income in the respective countries. Direct travel costs in some settings were kept low by local delivery system features such as community treatment observation. Lost productivity and costs for supplementary foods remained significant. CONCLUSIONS: Although it is not a straightforward exercise to determine the exact magnitude of likely savings, a shorter regimen would reduce out-of-pocket expenses incurred by patients in the most recent 2 months of the continuation phase and allow an earlier return to productive activities.

Are sputum samples of retreatment tuberculosis reaching the reference laboratories? A 9-year audit in Tanzania.

SETTING: One reference and three zonal laboratories and 500 health facilities managing retreatment tuberculosis (TB) patients in Tanzania. OBJECTIVES: The National Tuberculosis and Leprosy Programme (NTLP) requires that all notified cases of retreatment TB in Tanzania have sputum samples sent for culture and drug susceptibility testing (DST). This study determined 1) if the number of annually notified retreatment patients corresponded to the number of sputum samples received by the reference laboratories, and 2) the number of culture-positive samples and the number of cases undergoing DST. DESIGN: Nine-year audit of country-wide programme data from 2002 to 2010. RESULTS: Of the 40 940 retreatment TB patients notified by the NTLP, 3871 (10%) had their sputum samples received at the reference and zonal laboratories for culture and DST. A total of 3761 (97%) sputum samples were processed for culture, of which 1589 (42%) were found to be culture-positive and 1415 (89%) had DST performed. CONCLUSIONS: There is a >90% shortfall between notified retreatment cases and numbers of sputum samples received, cultured and assessed for DST at reference and zonal laboratories. Steps needed to address this problem are discussed.

New vaccines for the prevention of tuberculosis in human immunodeficiency virus infection.

The prevention of human immunodeficiency virus (HIV) associated tuberculosis (TB) remains challenging. Several vaccines against TB have advanced to clinical trials in patients with HIV infection. The DarDar Trial, a large, randomized, placebo-controlled efficacy trial conducted in Tanzania, has demonstrated that a multiple dose series of an inactivated whole cell mycobacterial vaccine is safe in HIV and can prevent HIV-associated TB in patients with childhood bacille Calmette-Guérin vaccination and CD4 counts of ≥200 cells/mm(3). These developments offer promise that in the not too distant future immunization with an effective vaccine against TB can be added to other strategies for the prevention of HIV-associated TB. This expanded approach is referred to as the Five 'I's': intensified case finding, infection control, isoniazid preventive therapy (IPT), initiation of antiretroviral therapy (ART), and immunization against TB. We encourage additional studies of new TB vaccines in HIV, and propose a strategy to reduce the risk of TB by integrating IPT, ART and immunization into routine HIV care. At the time of HIV diagnosis, patients with CD4 counts of ≥200 cells/mm(3) could receive immunization, IPT and, as appropriate, ART. In patients presenting with lower CD4 counts or already on ART, immunization could be initiated at CD4 counts of ≥200 cells/mm(3) to add to the protection afforded by IPT and ART.

A modelling framework to support the selection and implementation of new tuberculosis diagnostic tools.

Efforts to stimulate technological innovation in the diagnosis of tuberculosis (TB) have resulted in the recent introduction of several novel diagnostic tools. As these products come to market, policy makers must make difficult decisions about which of the available tools to implement. This choice should depend not only on the test characteristics (e.g., sensitivity and specificity) of the tools, but also on how they will be used within the existing health care infrastructure. Accordingly, policy makers choosing between diagnostic strategies must decide: 1) What is the best combination of tools to select? 2)Who should be tested with the new tools? and 3)Will these tools complement or replace existing diagnostics? The best choice of diagnostic strategy will likely vary between settings with different epidemiology (e.g., levels of TB incidence, human immunodeficiency virus co-infection and drug-resistant TB) and structural and resource constraints (e.g., existing diagnostic pathways, human resources and laboratory capacity). We propose a joint modelling framework that includes a tuberculosis (TB) transmission component (a dynamic epidemiological model) and a health system component (an operational systems model) to support diagnostic strategy decisions. This modelling approach captures the complex feedback loops in this system: new diagnostic strategies alter the demands on and performance of health systems that impact TB transmission dynamics which, in turn, result in further changes to demands on the health system. We demonstrate the use of a simplified model to support the rational choice of a diagnostic strategy based on health systems requirements, patient outcomes and population-level TB impact.

Evaluation of the Genotype® MTBDRplus assay as a tool for drug resistance surveys.

SETTING: A national tuberculosis (TB) drug resistance survey in Tanzania. OBJECTIVE: To compare the performance of the Genotype® MTBDRplus line-probe assay (LPA) on smear-positive sputum specimens with conventional culture and isoniazid (INH) plus rifampicin (RMP) drug susceptibility testing (DST). DESIGN: Mycobacterium tuberculosis isolates tested at the Tanzanian Central TB Reference Laboratory (CTRL) were submitted for quality assurance of phenotypic DST to its supranational reference laboratory (SRL), together with ethanol-preserved sputum specimens for LPA DST. RESULTS: Only 321 samples could be tested using LPA; of these, three were identified as being non-tuberculous mycobacteria using CTRL DST. Both tests had 269 sets with interpretable results. CTRL DST yielded almost the same number of interpretable results as LPA, with 90% concordance (κ = 0.612, P < 0.001). Five (1.9%) multidrug-resistant (MDR) strains, 46 (17.1%) resistant to INH only and 0 RMP only, were found by CTRL DST. For the LPA, these results were respectively 5 (1.9%), 26 (9.7%) and 2 (0.7%). With SRL DST as the gold standard, LPA was more accurate than CTRL DST for RMP, but missed almost half the INH-resistant samples. CONCLUSION: LPA applied directly on ethanol-preserved sputum specimens was similar to phenotypic DST in terms of yield of interpretable results. Although probably more accurate for RMP and MDR-TB, it appears to seriously underestimate INH resistance. Considering speed, easy and safe specimen transportation and low infrastructure requirements, LPA DST from sputum can be recommended for surveys in resource-poor settings.

Potential utility of empirical tuberculosis treatment for HIV-infected patients with advanced immunodeficiency in high TB-HIV burden settings.

The human immunodeficiency virus (HIV) and HIV-associated tuberculosis (TB-HIV) epidemics remain uncontrolled in many resource-limited regions, especially in sub-Saharan Africa. The scale of these epidemics requires the consideration of innovative bold interventions and 'out-of-the-box' thinking. To this end, a symposium entitled 'Controversies in HIV' was held at the 40th Union World Conference on Lung Health in Cancun, Mexico, in December 2009. The first topic debated, entitled 'Annual HIV testing and immediate start of antiretroviral therapy for all HIV-infected persons', received much attention at international conferences and in the literature in 2009. The second topic forms the subject of this article. The rationale for the use of empirical TB treatment is premised on the hypothesis that in settings worst affected by the TB-HIV epidemic, a subset of HIV-infected patients have such a high risk of undiagnosed TB and of associated mortality that their prognosis may be improved by immediate initiation of empirical TB treatment used in conjunction with antiretroviral therapy. In addition to morbidity and mortality reduction, additional benefits may include prevention of nosocomial TB transmission and TB preventive effect. Potential adverse consequences, however, may include failure to consider other non-TB diagnoses, drug co-toxicity, compromised treatment adherence, and logistical and resource challenges. There may also be general reluctance among national TB programmes to endorse such a strategy. Following fruitful debate, the conclusion that this strategy should be carefully evaluated in randomised controlled trials was strongly supported. This paper provides an in-depth consideration of this proposed intervention.

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.

Capacity of healthcare facilities in the implementation of direct observed treatment strategy for tuberculosis in Arumeru and Karatu districts, Tanzania.

Directly Observed Treatment Short course strategy (DOTS) has proved to have potential improvement in tuberculosis (TB) control in Tanzania. The objective of this cross sectional study was to assess the capacity of health facilities in implementing DOTS, in Arumeru and Karatu districts, Tanzania. Information sought included the capacity to offer TB service and availability of qualified staff and equipment for TB diagnosis. Information on availability and utilization of TB registers and treatment outcome for the year 2004 were also collected. A total of 111 health facilities were surveyed, 86 (77.5%) in Arumeru and 25 (22.5%) in Karatu. Only 23.4% (26/111) facilities were offering TB treatment services in the two districts. Majority 17/26 (65.38%) of them were government owned. Thirty eight (44.7%) facilities were offering TB laboratory services. All facilities with TB services (TB laboratory investigation and treatment) had TB registers. Seventy two (85.0%) of health facilities which do not provide any TB services had qualified clinical officers and at least a microscopy. Of the 339 cases notified in Arumeru in 2004, 187 (60.7%) had treatment outcome available, 124 (66.3%) were cured and 55 (29.4%) completed treatment. In Karatu 638 cases were notified in 2004, 305 (47.8%) had treatment outcome available, 68 (22.3%) cured and 165 (54.1%) completed treatment. In conclusion, the overall capacity for implementing DOTS among the facilities surveyed is found only in about 20% and 30% for clinical and laboratory components of DOTS, respectively. The capacity to provide TB diagnosis and treatment in Karatu district was relatively lower than Arumeru. It is important that capacity of the facilities is strengthened concurrently with the planned introduction of community-based DOTS in Tanzania.

The quality of sputum smear microscopy diagnosis of pulmonary tuberculosis in Dar es Salaam, Tanzania.

This study was carried out to determine the rate of agreement or disagreement of microscopy reading and culture positivity rate among smear positixe and negative specimens between peripheral tuberculosis diagnostic centres (PDCs) and Central Reference luberculosis laboratory (CTRL). In this study 13 PDCs in Dar es Salaam, Tanzania were involved. Lot Quality Assurance Sampling (LQAS) method was used to collect 222 sputum smear slides. A total of 190 morning sputum specimens with corresponding slides were selected for culture. First readings were done by technicians at PDCs and thereafter selected slides and specimens were sent to CTRL for re-examination and culture. Culture results were used as a gold standard. Of 222 slides selected, 214 were suitable for re-examination. Percentage of agreement of smear reading between PDCs and CTRL was 42.9% and 100% for positive and negative slides, respectively. Measure of agreement (Kappa statistic) was 0.5, indicating moderate agreement. Of 190 samples cultured, percentage of agreement between smear reading from PDCs and CTRL was 37% and 88.9% for smear positive and negative slides, respectively. Kappa statistic was 0.3 indicating poor-fair agreements. Comparison of smear reading from PDCs with culture showed sensitivity of 36.9% and specificity of 88.9%. Comparison of smear readings from CTRL with culture results showed sensitivity of 95.6% and specificity of 98.6%. In conclusion there was inadequate performance in diagnosis of TB using smear microscopy among peripheral diagnostic centres in Dar es Salaam. This calls for immediate and rigorous measures to improve the quality of smear microscopy. It is therefore important to strengthen the capacity of laboratory personnel in smear microscopy techniques through supportive supervision and training.

Effectiveness of community-based directly observed treatment for tuberculosis in an urban setting in Tanzania: a randomised controlled trial.

SETTING: An urban district in Dar es Salaam city with a high tuberculosis (TB) caseload. OBJECTIVE: To evaluate the effectiveness of community-based direct observation of treatment (DOT) using guardians and former TB patients compared to hospital-based DOT in an urban setting in Tanzania. DESIGN: Unblinded randomised control trial conducted in five sites under operational conditions in Temeke district. No changes to existing treatment delivery were made other than randomisation. The main outcome measure was treatment success. Analysis was by intention to treat. FINDINGS: A total of 587 new tuberculosis patients were enrolled. Among enrolled patients, 260 were assigned to community-based DOT using guardians and former TB patients and 327 to health facility-based DOT. Both DOT options gave similar treatment outcomes. Treatment success rate among patients under community and health facility-based DOT were 85% and 83%, respectively (OR 1.17, 95%CI 0.75-1.83). CONCLUSION: Community-based DOT is as effective as health facility-based DOT and can achieve good treatment outcomes, even in countries with well functioning National Tuberculosis Programmes.

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.

Density of tuberculin skin reaction and its association with tuberculosis infection as defined by dual tuberculin testing.

OBJECTIVE: To determine whether the density of tuberculin skin reactions is associated with tuberculosis infection. METHODS: In a national tuberculin survey in Tanzania, 1983-1987, all eligible children in a random sub-sample of schools underwent dual tuberculin skin testing with PPD-RT23 and PPD-scrofulaceum. The density of reactions to RT23 was classified as proposed by Palmer. A larger reaction to PPD-scrofulaceum than to PPD-RT23 is suggestive of infection with environmental mycobacteria. Tuberculosis infection was defined based on dual skin test results applying a range of possible definitions. RESULTS: A total of 10,782 children aged 5-14 years and without BCG scar were included in the analysis. Large skin reactions to RT23 were generally firmer than small ones. After taking the size of the skin reaction to RT23 into account, its density was not associated with the size of the skin reaction against PPD-scrofulaceum. In particular, the density of reactions in the range 6-11 mm was not associated with tuberculosis infection according to any of the definitions used. CONCLUSION: This study suggests that the density of reaction was not associated with tuberculosis infection in Tanzanian school children after taking the size of the induration into account.