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The use of molecular genetic tests as a part of tuberculosis patients examination made it possible to reduce the time for TB diagnosis and determination of drug resistance (DR) of M. tuberculosis (MTB) in Arkhangelsk Region. Early detection of multiple drug resistant tuberculosis (MDR TB) made it possible to prescribe the adequate chemotherapy regimen promptly and thus to improve treatment outcomes.\ud The objective of the study: to evaluate the results of treatment of MDR TB patients in whom MDR TB was diagnosed by molecular genetic tests. It was assumed that the introduction of molecular genetic tests would result in improved treatment outcomes in MDR TB patients [(the research project of the International Union Against Tuberculosis and Lung Diseases and Tuberculosis Control Program of Arkhangelsk Region of the PROVE-IT LPA (Policy Relevant Outcomes from Validating Evidence on Impact of Line Probe Assays)].\ud Subjects: 295 MDR TB patients detected in Arkhangelsk Region were enrolled in the study. MDR TB was detected by molecular genetic tests in the main group (132 patients) and by culture in the control group (163 patients). Patients from both groups received the standard chemotherapy regimen. Chemotherapy outcomes were compared in both groups.\ud Results. Treatment outcomes were better in the group (MGT group) where molecular genetic tests were used for drug susceptibility testing (p = 0.003) versus the comparison group where the culture was used. Effective treatment was documented more frequently (65.2%) in the MGT group versus the comparison group (44.8%). All-cause mortality was lower in the MGT group (7.6%) than in the comparison group (15.9%). There were no statistically significant differences between the groups in the time when sputum conversion (by smear and culture) was achieved.\ud Key words: tuberculosis, multiple drug resistant M. tuberculosis, molecular genetic diagnostic tests

BackgroundThe prevalence of diseases other than TB detected during chest X-ray (CXR) screening is unknown in sub-Saharan Africa. This represents a missed opportunity for identification and treatment of potentially significant disease. Our aim was to describe and quantify non-TB abnormalities identified by TB-focused CXR screening during the 2016 Kenya National TB Prevalence Survey.MethodsWe reviewed a random sample of 1140 adult (≥15 years) CXRs classified as ‘abnormal, suggestive of TB’ or ‘abnormal other’ during field interpretation from the TB prevalence survey. Each image was read (blinded to field classification and study radiologist read) by two expert radiologists, with images classified into one of four major anatomical categories and primary radiological findings. A third reader resolved discrepancies. Prevalence and 95% CIs of abnormalities diagnosis were estimated.FindingsCardiomegaly was the most common non-TB abnormality at 259 out of 1123 (23.1%, 95% CI 20.6% to 25.6%), while cardiomegaly with features of cardiac failure occurred in 17 out of 1123 (1.5%, 95% CI 0.9% to 2.4%). We also identified chronic pulmonary pathology including suspected COPD in 3.2% (95% CI 2.3% to 4.4%) and non-specific patterns in 4.6% (95% CI 3.5% to 6.0%). Prevalence of active-TB and severe post-TB lung changes was 3.6% (95% CI 2.6% to 4.8%) and 1.4% (95% CI 0.8% to 2.3%), respectively.InterpretationBased on radiological findings, we identified a wide variety of non-TB abnormalities during population-based TB screening. TB prevalence surveys and active case finding activities using mass CXR offer an opportunity to integrate disease screening efforts.FundingNational Institute for Health Research (IMPALA-grant reference 16/136/35).

Background Implementation of an effective Tuberculosis Routine Surveillance System in low-income countries like Tanzania is problematic, despite being an essential tool for the detection and effective monitoring of drug resistant tuberculosis. Long delays in specimen transportation from the facilities to reference laboratory and results dissemination back to the health facilities, result in poor patient management, particularly where multidrug-resistant tuberculosis disease is present. Methods Following a detailed qualitative study, a pilot intervention of a revised Tuberculosis Routine Surveillance System was implemented in Mwanza region, Tanzania. This included the use of rapid molecular methods for the detection of both tuberculosis and drug resistance using Xpert MTB/RIF in some Mwanza sites, the use of Xpert MTB/RIF and Line Probe Assay at the Central Tuberculosis Reference Laboratory, a revised communication strategy and interventions to address the issue of poor form completion. A before and after comparison of the intervention on the number of drug resistant tuberculosis cases identified and the time taken for results feedback to the requesting site was reported. Results The revised system for previously treated cases tested at the Central Reference Laboratory was able to obtain the following findings; the number of cases tested increased from 75 in 2016 to 185 in 2017. The times for specimen transportation from health facilities to the reference laboratory were reduced by 22% (from 9 to 7 days). The median time for the district to receive results was reduced by 36% (from 11 to 7 days). Overall the number of drug resistant tuberculosis cases starting treatment increased by 67% (from 12 to 20). Conclusion Detection of drug resistance could significantly be enhanced, and delays reduced by introduction of new technologies and improved routine surveillance system, including better communication using mobile applications such as ‘WhatsApp’ and close follow-ups. A larger scale study is now merited to ascertain if these benefits are robust across different contexts.

SETTING: Eight tuberculosis treatment sites in Cavite Province, the Philippines, including two sites specialising in management of multidrug-resistant tuberculosis (MDR-TB).OBJECTIVE: To evaluate costs incurred by TB patients and to determine the proportion of households that faced catastrophic costs, then to consider cost survey responses alongside results of detailed patient-pathway modelling.DESIGN: Clustered cross-sectional survey using a field testing version of the WHO TB patient-costing tool and protocol; face-to-face interviews with 194 patients conducted in May–August 2016. Costs included direct-medical, direct non-medical and indirect costs using the human capital approach. Patients were deemed to incur catastrophic expenditure if TB-related costs exceeded 20% of annual household income. Patient pathways were modelled following multiple health staff interviews.RESULTS: Estimated mean cost incurred by patients with drug-susceptible TB was US$321 vs. $2356 for MDR-TB patients. Catastrophic costs were suffered by 28% of drug-susceptible and 80% of MDR-TB patients, with lost income being the largest contributor. Patient-pathway modelling suggested most patients had under-reported health visits.CONCLUSION: Survey results indicate that patient costs are large for all patients in Cavite, particularly for MDR-TB patients. Patient-pathway modelling suggests these costs are an underestimate due to poor recollection of health visits, suggesting that the WHO instrument and protocol could be improved to better capture the diagnostic journey.

BackgroundCommunity-based screening for tuberculosis (TB) could improve detection but is resource intensive. We set out to evaluate the accuracy of computer-aided TB screening using digital chest X-ray (CXR) to determine if this approach met target product profiles (TPP) for community-based screening.MethodsCXR images from participants in the 2016 Kenya National TB Prevalence Survey were evaluated using CAD4TBv6 (Delft Imaging), giving a probabilistic score for pulmonary TB ranging from 0 (low probability) to 99 (high probability). We constructed a Bayesian latent class model to estimate the accuracy of CAD4TBv6 screening compared to bacteriologically-confirmed TB across CAD4TBv6 threshold cut-offs, incorporating data on Clinical Officer CXR interpretation, participant demographics (age, sex, TB symptoms, previous TB history), and sputum results. We compared model-estimated sensitivity and specificity of CAD4TBv6 to optimum and minimum TPPs.ResultsOf 63,050 prevalence survey participants, 61,848 (98%) had analysable CXR images, and 8,966 (14.5%) underwent sputum bacteriological testing; 298 had bacteriologically-confirmed pulmonary TB. Median CAD4TBv6 scores for participants with bacteriologically-confirmed TB were significantly higher (72, IQR: 58-82.75) compared to participants with bacteriologically-negative sputum results (49, IQR: 44-57, pConclusionsCAD4TBv6 met the optimal TPP for TB community screening. To optimise screening accuracy and efficiency of confirmatory sputum testing, we recommend that an adaptive approach to threshold setting is adopted based on participant characteristics.Take home messageCAD4TBv6 met the optimal WHO target product profile for a community TB screening tool. Specificity was lower in adults with previous TB and those aged 41 years or older; an adaptive approach to setting CAD thresholds will likely be required to optimize use.

Background Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommend...

BackgroundMitigating the socioeconomic impact of tuberculosis (TB) is key to the WHO End TB Strategy. However, little known about socioeconomic well-being beyond TB-treatment completion. In this mixed-methods study, we describe socioeconomic outcomes after TB-disease in urban Blantyre, Malawi, and explore pathways and barriers to financial recovery.MethodsAdults ≥15 years successfully completing treatment for a first episode of pulmonary TB under the National TB Control Programme were prospectively followed up for 12 months. Socioeconomic, income, occupation, health seeking and cost data were collected. Determinants and impacts of ongoing financial hardship were explored through illness narrative interviews with purposively selected participants.Results405 participants were recruited from February 2016 to April 2017. Median age was 35 years (IQR: 28–41), 67.9% (275/405) were male, and 60.6% (244/405) were HIV-positive. Employment and incomes were lowest at TB-treatment completion, with limited recovery in the following year: fewer people were in paid work (63.0% (232/368) vs 72.4% (293/405), p=0.006), median incomes were lower (US$44.13 (IQR: US$0–US$106.15) vs US$72.20 (IQR: US$26.71–US$173.29), pConclusionsTB-affected households remain economically vulnerable even after TB-treatment completion, with limited recovery in income and employment, persistent financial strain requiring dissaving, and ongoing school interruptions. Measures of the economic impact of TB disease should include the post-TB period. Interventions to protect the long-term health and livelihoods of TB survivors must be explored.

BackgroundPost-tuberculosis lung damage (PTLD) is a recognised consequence of pulmonary TB (pTB). However, little is known about its prevalence, patterns and associated outcomes, especially in sub-Saharan Africa and HIV-positive adults.MethodsAdult (≥15 years) survivors of a first episode of pTB in Blantyre, Malawi, completed the St George’s Respiratory Questionnaire, 6-minute walk test, spirometry and high-resolution CT (HRCT) chest imaging at TB treatment completion. Symptom, spirometry, health seeking, TB-retreatment and mortality data were collected prospectively to 1 year. Risk factors for persistent symptoms, pulmonary function decline and respiratory-related health-seeking were identified through multivariable regression modelling.ResultsBetween February 2016 and April 2017, 405 participants were recruited. Median age was 35 years (IQR: 28 to 41), 77.3% (313/405) had had microbiologically proven pTB, and 60.3% (244/403) were HIV-positive. At pTB treatment completion, 60.7% (246/405) reported respiratory symptoms, 34.2% (125/365) had abnormal spirometry, 44.2% (170/385) had bronchiectasis ≥1 lobe and 9.4% (36/385) had ≥1 destroyed lobe on HRCT imaging. At 1 year, 30.7% (113/368) reported respiratory symptoms, 19.3% (59/305) and 14.1% (43/305) of patients had experienced declines in FEV1 or FVC of ≥100 mL, 16.3% (62/380) had reported ≥1 acute respiratory event and 12.2% (45/368) had symptoms affecting their ability to work.ConclusionsPTLD is a common and under-recognised consequence of pTB that is disabling for patients and associated with adverse outcomes beyond pTB treatment completion. Increased efforts to prevent PTLD and guidelines for management of established disease are urgently needed. Low-cost clinical interventions to improve patient outcomes must be evaluated.

SETTING: Cape Town, South Africa, where Xpert® MTB/RIF was introduced as a screening test for all presumptive tuberculosis (TB) cases. OBJECTIVE: To compare laboratory costs of smear/culture- and Xpert-based tuberculosis (TB) diagnostic algorithms in routine operational conditions. METHODS: Economic costing was undertaken from a laboratory perspective, using an ingredients-based costing approach. Cost allocation was based on reviews of standard operating procedures and laboratory records, timing of test procedures, measurement of laboratory areas and manager interviews. We analysed laboratory test data to assess overall costs and cost per pulmonary TB and multidrug-resistant TB (MDR-TB) case diagnosed. Costs were expressed as 2013 Consumer Price Index-adjusted values. RESULTS: Total TB diagnostic costs increased by 43%, from US$440 967 in the smear/culture-based algorithm (April–June 2011) to US$632 262 in the Xpert-based algorithm (April–June 2013). The cost per TB case diagnosed increased by 157%, from US$48.77 (n = 1601) to US$125.32 (n = 1281). The total cost per MDR-TB case diagnosed was similar, at US$190.14 and US$183.86, with 95 and 107 cases diagnosed in the respective algorithms. CONCLUSION: The introduction of the Xpert-based algorithm resulted in substantial cost increases. This was not matched by the expected increase in TB diagnostic efficacy, calling into question the sustainability of this expensive new technology.

BackgroundRoutine surveillance is required to monitor the performance of tuberculosis diagnostic programme and is essential for the rapid detection of drug resistance. The main objective of this study was to explore the effectiveness and stakeholder perception of the current routine surveillance system for previously treated tuberculosis cases in Tanzania with a view to identify interventions to improve and accelerate positive patient outcomes.MethodsA study using quantitative and qualitative methods of data collection including in-depth interviews and focus group discussions with health care service providers was conducted in four regions. Quantitative data were extracted from the routine databases to assess performance.ResultsQuantitative findings from 2011 to 2013 showed 2,750 specimens from previously treated TB cases were received at the reference laboratory. The number increased year on year, but even in the most recent year was only 61% of that expected. The median and interquartile range of turnaround time in days from specimen reception to results reported for smear microscopy, culture and drug susceptibility testing were 1(1, 1), 61(43, 71) and 129(72, 170) respectively. Contaminated specimens were reported in 3.6% of cases. The qualitative analysis showed the system of sending specimens using postal services was seen to be efficient by participants. However, there were many challenges and significant delays in specimens reaching the reference laboratory associated with lack of funds to transfer specimens, weak form completion, inadequate training and poor supervision. These all adversely affected the implementation of the routine surveillance system.ConclusionsMany issues limit the effectiveness of the routine surveillance system in Tanzania. Priority areas for strengthening are; specimen transportation, supervision and availability of commodities. A pilot study of a revised routine surveillance system that takes into account the observations from this study alongside improved access to drug susceptibility testing using Xpert MTB/RIF should be considered.

SETTING: There is a high burden of respiratory disease in sub-Saharan Africa. To address this problem, the World Health Organization launched the ‘Practical approach to Lung Health' (PAL), i.e., locally applicable integrated syndromic algorithms, to improve primary care management of these diseases. OBJECTIVE: To examine the evidence for the impact of PAL on the diagnosis and management of tuberculosis (TB) and other common respiratory problems in sub-Saharan Africa. DESIGN: A systematic review of MEDLINE (1998–2015), EMBASE (1998–2015) and CINAHL (1998–2015) was conducted to find trials evaluating PAL implementation in sub-Saharan Africa. RESULTS: Five studies were found, evaluating three PAL variations: PAL in South Africa (PALSA), PALSA with integrated human immunodeficiency virus treatment (PALSA PLUS) and PAL in Malawi using lay health workers (PALM/LHW). PALSA increased TB diagnosis (OR 1.72, 95%CI 1.04–2.85), as did PALSA PLUS (OR 1.25, 95%CI 1.01–1.55). Cure or completion rates in retreatment cases in PALSA and PALSA PLUS were significantly improved (OR 1.78, 95%CI 1.13–2.76). PALM/LHW, which examined TB treatment success, found no significant improvement (P = 0.578). CONCLUSION: The limited research performed shows that PAL can be effective in TB diagnosis and partial treatment success; however, more evidence is needed to assess its effects on other respiratory diseases, especially in wider sub-Saharan Africa.

Background\ud \ud The implementation of rapid drug susceptibility testing (DST) is a current global priority for TB control. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pDR-TB) evaluated under field conditions in high burden countries.\ud \ud Methods\ud \ud Observational study of pDR-TB patients referred by primary and secondary health units. TB reference centers addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culture positive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by a physician to start anti-TB treatment. The outcome measures were median time from triage to initiating appropriate anti-TB treatment, empirical treatment and, the treatment outcomes.\ud \ud Results\ud \ud Between February,16th, 2011 and February, 15th, 2012, among 175 pDR TB cases, 110 (63.0%) confirmed TB cases with DST results were enrolled. Among study participants, 72 (65.5%) were male and 62 (56.4%) aged 26 to 45 years. At triage, empirical treatment was given to 106 (96.0%) subjects. Among those, 85 were treated with first line drugs and 21 with second line. Median time for DST results was 69.5 [interquartile - IQR: 35.7–111.0] days and, for initiating appropriate anti-TB treatment, the median time was 1.0 (IQR: 0–41.2) days. Among 95 patients that were followed-up during the first 6 month period, 24 (25.3%; IC: 17.5%–34.9%) changed or initiated the treatment after DST results: 16/29 MDRTB, 5/21 DR-TB and 3/45 DS-TB cases. Comparing the treatment outcome to DS-TB cases, MDRTB had higher proportions changing or initiating treatment after DST results (p = 0.01) and favorable outcomes (p = 0.07).\ud \ud Conclusions\ud \ud This study shows a high rate of empirical treatment and long delay for DST results. Strategies to speed up the detection and early treatment of drug resistant TB should be prioritized.

Background\ud User fees have generally fallen out of favor across Africa, and they have been associated with reductions in access to healthcare. We examined the effects of the introduction and removal of user fees on outpatient attendances and new diagnoses of HIV, malaria, and tuberculosis in Neno District, Malawi where user fees were re-instated at three of 13 health centres in 2013 and subsequently removed at one of these in 2015.\ud \ud Methods\ud We conducted two analyses. Firstly, an unadjusted comparison of outpatient visits and new diagnoses over three periods between July 2012 and October 2015: during the period with no user fees, at the re-introduction of user fees at four centres, and after the removal of user fees at one centre. Secondly, we estimated a linear model of the effect of user fees on the outcome of interest that controlled for unobserved health centre effects, monthly effects, and a linear time trend.\ud \ud Results\ud The introduction of user fees was associated with a change in total attendances of −68 % [95 % CI: −89 %, −12 %], similar reductions were observed for new malaria and HIV diagnoses. The removal of user fees was associated with an increase in total attendances of 352 % [213 %, 554 %] with similar increases for malaria diagnoses. The results were not sensitive to control group or model specification.\ud \ud Conclusions\ud User fees for outpatient healthcare services present a barrier to patients accessing healthcare and reduce detection of serious infectious diseases.

This research was supported by Public Health England and the Centre for Applied Health Research and Delivery, Liverpool School of Tropical Medicine (LSTM). Objectives. Tuberculosis cohort audit (TBCA) was introduced across the North West (NW) of England in 2012 as an ongoing, multidisciplinary, systematic case review process, designed to improve clinical and public health practice. TBCA has not previously been introduced across such a large and socioeconomically diverse area in England, nor has it undergone formal, qualitative evaluation. This study explored health professionals' experiences of the process after 1515 cases had been reviewed. Design. Qualitative study using semistructured interviews. Respondents were purposively sampled from 3 groups involved in the NW TBCA: (1) TB nurse specialists, (2) consultant physicians and (3) public health practitioners. Data from the 26 respondents were triangulated with further interviews with key informants from the TBCA Steering Group and through observation of TBCA meetings. Analysis. Interview transcripts were analysed thematically using the framework approach. Results. Participants described the evolution of a valuable 'community of practice' where interprofessional exchange of experience and ideas has led to enhanced mutual respect between different roles and a shared sense of purpose. This multidisciplinary, regional approach to TB cohort audit has promoted local and regional team working, exchange of good practices and local initiatives to improve care. There is strong ownership of the process from public health professionals, nurses and clinicians; all groups want it to continue. TBCA is regarded as a tool for quality improvement that improves patient safety. Conclusions. TBCA provides peer support and learning for management of a relatively rare, but important infectious disease through discussion in a no-blame atmosphere. It is seen as an effective quality improvement strategy which enhances TB care, control and patient safety. Continuing success will require increased engagement of consultant physicians and public health practitioners, a secure and ongoing funding stream and establishment of clear reporting mechanisms within the public health system. Publisher PDF

Costs incurred during care-seeking for chronic respiratory disease are a major problem with severe consequences for socio-economic status and health outcomes. Most of the published evidence to date relates to tuberculosis (TB) and there is a lack of information for the major non-communicable chronic respiratory diseases: asthma and chronic obstructive pulmonary disease (COPD). International policy is recognising the need to address this problem and measure progress towards eliminating catastrophic care-seeking costs (see the post-2015 TB strategy). Current tools for measuring, defining, and understanding the full consequences of catastrophic care-seeking costs are inadequate. We propose two areas of work which are urgently needed to prepare health systems and countries for the burden of chronic lung disease that will fall on poor populations in the coming 10-20 years: a) Rapid scale up of the number and scope of studies of patient costs associated with chronic non-communicable respiratory disease. b) Work towards deeper understanding and effective measurement of catastrophic care-seeking costs. This will produce a range of indicators, such as dissaving, which can more effectively inform health policy decision-making for lung health. These will also be useful for other health problems. We argue that reduction in care-seeking costs will be a key monitoring indicator for improvements in lung health in particular, and health in general, in the coming 10 to 20 years.

Background In developing countries like Malawi, further investigation is rare after patients with chronic cough test negative for tuberculosis. Chronic airways disease has presentations that overlap with tuberculosis. However, chronic airways disease is often unrecognised due to a lack of diagnostic services. Within developing countries, referral systems at primary health care level are weak and patients turn to unskilled informal health providers to seek health care. Delayed diagnosis and treatment of these diseases facilitates increased severity and tuberculosis transmission. The World Health Organisation developed the Practical Approach to Lung Health strategy which has been shown to improve the management of both tuberculosis and chronic airways disease. The guidelines address the need for integrated guidelines for tuberculosis and chronic airways disease. Engaging with informal health providers has been shown to be effective in improving health services uptake. However, it is not known whether engaging community informal health providers would have a positive impact in the implementation of the Practical Approach to Lung Health strategy. We will use a cluster randomised controlled trial to determine the effect of using the two interventions to improve case detection and treatment of patients with tuberculosis and chronic airways disease. Methods A three-arm cluster randomised trial design will be used. A primary health centre catchment population will form a cluster, which will be randomly allocated to one of the arms. The first arm personnel will receive the Practical Approach to Lung Health strategy intervention. In addition to this strategy, the second arm personnel will receive training of informal health providers. The third arm is the control. The effect of interventions will be evaluated by community surveys. Data regarding the diagnosis and management of chronic cough will be gathered from primary health centres. Discussion This trial seeks to determine the effect of Informal Health Provider and Practical Approach to Lung Health interventions on the detection and management of chronic airways disease and tuberculosis at primary care level in Malawi. Trial registration The unique identification number for the registry is PACTR201411000910192 – 21 November 2014 Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1068-4) contains supplementary material, which is available to authorized users.

Tuberculosis (TB) is a major global public health problem which affects poorest individuals the worst. A high proportion of patients incur 'catastrophic costs' which have been shown to result in severe financial hardship and adverse health outcomes. Data on catastrophic cost incidence is not routinely collected, and current definitions of this indicator involve several practical and conceptual barriers to doing so. We analysed data from TB programmes in India (Bangalore), Bangladesh and Tanzania to determine whether dissaving (the sale of assets or uptake of loans) is a useful indicator of financial hardship., info:eu-repo/semantics/published

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.

This study aims to understand the contextual barriers to accessing timely TB diagnosis after first seeking care, especially among the poor and vulnerable in rural China. Both quantitative and qualitative methods were used to elicit the experiences and perspectives of TB patients and suspected TB patients, community residents, health providers and policy makers in poor, rural areas of four provinces. Between 30 and 60% of patients across the four provinces experienced a delay in receiving a diagnosis after first seeking care. Most patients had to visit health facilities more than once before diagnosis, with 17-30% patients making more than 6 visits. These delays and multiple visits mainly occurred because of the limited capacity of health providers to recognize TB, and financial disincentives to refer patients to TB dispensaries, due to the pressures of the cost recovery system. Poverty and socio-economic disadvantage amongst patients also influenced their capability to seek further care to obtain a reliable diagnosis. Qualitative data showed that women and the elderly patients were likely to experience more 'system' delay, and these findings were to some extent supported by the survey. The study concludes that 'system' delay is a serious problem, which is influenced by the financing mechanisms for both TB control and general health services as well as poverty and disadvantage amongst patients. This requires a comprehensive strategy to shorten 'system' delay in order to enable successful DOTS expansion, including developing appropriate financing mechanisms to improve general provider capacity and encourage referral, as well as measures to improve financial and social access to services for potential TB patients.

SETTING: Ten primary health care facilities in Cape Town, South Africa, 2010–2013.\ud \ud OBJECTIVE: A comparison of costs incurred by patients in GenoType® MDRTBplus line-probe assay (LPA) and Xpert® MTB/RIF-based diagnostic algorithms from symptom onset until treatment initiation for multidrug-resistant tuberculosis (MDR-TB).\ud \ud METHODS: Eligible patients identified from laboratory and facility records were interviewed 3–6 months after treatment initiation and a cost questionnaire completed. Direct and indirect costs, individual and household income, loss of individual income and change in household income were recorded in local currency, adjusted to 2013 costs and converted to $US.\ud \ud RESULTS: Median number of visits to initiation of MDR-TB treatment was reduced from 20 to 7 (P < 0.001) and median costs fell from US$68.1 to US$38.3 (P = 0.004) in the Xpert group. From symptom onset to being interviewed, the proportion of unemployed increased from 39% to 73% in the LPA group (P < 0.001) and from 53% to 89% in the Xpert group (P < 0.001). Median household income decreased by 16% in the LPA group and by 13% in the Xpert group.\ud \ud CONCLUSION: The introduction of an Xpert-based algorithm brought relief by reducing the costs incurred by patients, but loss of employment and income persist. Patients require support to mitigate this impact.

BACKGROUND: \ud \ud The use of liquid medium (MGIT960) for tuberculosis (TB) diagnosis was recommended by WHO in 2007. However, there has been no evaluation of its effectiveness on clinically important outcomes.\ud \ud METHODS AND FINDINGS: \ud \ud A pragmatic trial was carried out in a tertiary hospital and a secondary health care unit in Rio de Janeiro City, Brazil. Participants were 16 years or older, suspected of having TB. They were excluded if only cerebral spinal fluid or blood specimens were available for analysis. MGIT960 technique was compared with the Lowenstein-Jensen (LJ) method for laboratory diagnosis of active TB. Primary outcome was the proportion of patients who had their initial medical management changed within 2 months after randomisation. Secondary outcomes were: mean time for changing the procedure, patient satisfaction with the overall treatment and adverse events. Data were analysed by intention-to-treat. Between April 2008 and September 2011, 693 patients were enrolled (348 to MGIT, 345 to LJ). Smear and culture results were positive for 10% and 15.7% of participants, respectively. Patients in the MGIT arm had their initial medical management changed more frequently than those in the LJ group (10.1% MGIT vs 3.8% LJ, RR 2.67 95% CI 1.44-.96, p = 0.002, NNT 16, 95% CI 10-39). Mean time for changing the initial procedure was greater in LJ group at both sites: 20.0 and 29.6 days in MGIT group and 52.2 and 64.3 in LJ group (MD 33.5, 95% CI 30.6-36.4, p = 0.0001). No other important differences were observed.\ud \ud CONCLUSIONS: \ud \ud This study suggests that opting for the MGIT960 system for TB diagnosis provides a promising case management model for improving the quality of care and control of TB.\ud \ud TRIAL REGISTRATION: \ud \ud Controlled-Trials.com ISRCTN79888843.

Laboratory services are run down in many low-income countries, severely constraining their input to patient care and disease surveillance. There are few data about the quality and cost of individual components of the laboratory service in poorer countries, yet this information is essential if optimal use is to be made of scarce resources. Staff time, range of tests, workload, and safety procedures were monitored over 12 months (1997-98) in a typical district hospital laboratory in Malawi. Data were collected to calculate the total economic cost of these services. Of the 31203 tests performed, 84% were to support blood transfusion and diagnosis of malaria and tuberculosis (TB). Test quality was reasonable for malaria and TB microscopy and blood transfusion, but poor for haemoglobin estimation. The cost per test ranged from US dollars 0.35 for haemoglobin to US dollars 11.7 per unit of blood issued and the total annual cost of the laboratory service was US dollars 32618. Blood transfusion and microscopy for malaria and TB comprised the majority of tests. Ensuring that these tests are of the highest quality will therefore have the most impact in reducing wastage of laboratory resources. Inadequate quality of haemoglobin estimations is a particular problem. The findings of this study are likely to be relevant to other low-income countries with similar disease burdens.

SUMMARY 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. KEY W ORDS: patient preferences; treatment costs; poverty; access

BackgroundIn the Arkhangelsk region of Northern Russia, multidrug-resistant (MDR) tuberculosis (TB) rates in new cases are amongst the highest in the world. In 2014, MDR-TB rates reached 31.7% among new cases and 56.9% among retreatment cases. The development of new diagnostic tools allows for faster detection of both TB and MDR-TB and should lead to reduced transmission by earlier initiation of anti-TB therapy.Study aimThe PROVE-IT (Policy Relevant Outcomes from Validating Evidence on Impact) Russia study aimed to assess the impact of the implementation of line probe assay (LPA) as part of an LPA-based diagnostic algorithm for patients with presumptive MDR-TB focusing on time to treatment initiation with time from first-care seeking visit to the initiation of MDR-TB treatment rather than diagnostic accuracy as the primary outcome, and to assess treatment outcomes. We hypothesized that the implementation of LPA would result in faster time to treatment initiation and better treatment outcomes.MethodsA culture-based diagnostic algorithm used prior to LPA implementation was compared to an LPA-based algorithm that replaced BacTAlert and Löwenstein Jensen (LJ) for drug sensitivity testing. A total of 295 MDR-TB patients were included in the study, 163 diagnosed with the culture-based algorithm, 132 with the LPA-based algorithm.ResultsAmong smear positive patients, the implementation of the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 50 and 66 days compared to the culture-based algorithm (BacTAlert and LJ respectively, pConclusionThe results of the study suggest that the introduction of LPA leads to faster time to MDR diagnosis and earlier treatment initiation as well as better treatment outcomes for patients with MDR-TB. These findings also highlight the need for further improvements within the health system to reduce both patient and diagnostic delays to truly optimize the impact of new, rapid diagnostics.

Background\ud Early access to tuberculosis diagnosis and treatment remains a challenge in developing countries. General use of informal providers such as storekeepers is common. The aim of this study was to determine the effectiveness and acceptability of a storekeeper-based referral system for TB suspects in urban settings of Lilongwe, Malawi.\ud \ud Methods\ud The referral system intervention was implemented in two sub-districts. This was evaluated using a pre and post comparison as well as comparison with a third sub-district designated as the control. The intervention included training of storekeepers to detect and refer clients with chronic cough using predesigned referral letters along with monitoring and supervision. Data from a community based chronic cough survey and an audit of health centre records were used to measure its effectiveness. Focus group discussions and in-depth interviews were carried out to document acceptability of the intervention with the different stakeholders.\ud \ud Results\ud Following the intervention, the mean patient delay appeared lower in the intervention than comparison areas (2.14 weeks (SD 5.8) vs 8.8 weeks (SD 15.1)). However, after adjusting for confounding variables this difference was not significant (p = 0.07). After the intervention the proportion of the population diagnosed with smear positive TB in the intervention sites (1.2 per 1000) was significantly higher than in the comparison area (0.6 per 1000, p

This study, nested within a clinical trial, by Luis Cuevas and colleagues finds that LED-FM microscopy has higher sensitivity but lower specificity than Zn microscopy for detecting tuberculosis in sputum samples., Background The diagnosis of tuberculosis (TB) in resource-limited settings relies on Ziehl-Neelsen (ZN) smear microscopy. LED fluorescence microscopy (LED-FM) has many potential advantages over ZN smear microscopy, but requires evaluation in the field. The aim of this study was to assess the sensitivity/specificity of LED-FM for the diagnosis of pulmonary TB and whether its performance varies with the timing of specimen collection. Methods and Findings Adults with cough ≥2 wk were enrolled consecutively in Ethiopia, Nepal, Nigeria, and Yemen. Sputum specimens were examined by ZN smear microscopy and LED-FM and compared with culture as the reference standard. Specimens were collected using a spot-morning-spot (SMS) or spot-spot-morning (SSM) scheme to explore whether the collection of the first two smears at the health care facility (i.e., “on the spot”) the first day of consultation followed by a morning sample the next day (SSM) would identify similar numbers of smear-positive patients as smears collected via the SMS scheme (i.e., one on-the-spot-smear the first day, followed by a morning specimen collected at home and a second on-the-spot sample the second day). In total, 529 (21.6%) culture-positive and 1,826 (74.6%) culture-negative patients were enrolled, of which 1,156 (49%) submitted SSM specimens and 1,199 (51%) submitted SMS specimens. Single LED-FM smears had higher sensitivity but lower specificity than single ZN smears. Using two LED-FM or two ZN smears per patient was 72.8% (385/529, 95% CI 68.8%–76.5%) and 65.8% (348/529, 95% CI 61.6%–69.8%) sensitive (p, Editors' Summary Background Tuberculosis is a global public health problem. Every year, about 1.7 million people die from this contagious bacterial infection, and about 9 million new cases occur, mainly in low- and middle-income countries. Mycobacterium tuberculosis, which causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze, and usually infects the lungs (pulmonary tuberculosis). Symptoms of tuberculosis include a persistent cough, weight loss, and night sweats. Because tuberculosis is easily transmitted and potentially deadly, it is important that it is diagnosed quickly and accurately and immediately treated. The “gold standard” diagnostic test for tuberculosis is mycobacterial culture (in liquid or solid medium), in which laboratory technicians try to grow M. tuberculosis from sputum (mucus brought up from the lungs by coughing). However, this test is expensive, so most patients suspected of having pulmonary tuberculosis in resource-limited countries are investigated using sputum smear microscopy. In this cheaper but less sensitive test, sputum samples are “smeared” onto microscope slides, stained with Ziehl-Neelsen (ZN) dye, and then examined with a microscope for the presence of M. tuberculosis. Why Was This Study Done? With smear microscopy, multiple samples have to be examined to increase the test's sensitivity (the proportion of patients with culture-positive tuberculosis that the test detects). Because each smear examination takes up to 10 minutes, tuberculosis diagnosis with ZN smear microscopy creates a large laboratory workload. A variant form of smear microscopy—light-emitting-diode fluorescence microscopy (LED-FM)—could reduce this workload. With LED-FM, smears stained with a fluorescent dye can be examined in a quarter of the time it takes to examine ZN smears. In this study, the researchers evaluate the sensitivity and specificity (the proportion of people with a negative smear among people without tuberculosis; a high specificity indicates a low false-positive rate) of LED-FM using samples collected in a trial undertaken in four resource-limited countries (Ethiopia, Nepal, Nigeria, and Yemen) to investigate two schemes for sputum sample collection. In the spot-morning-spot (SMS) scheme, patients provide an on-the-spot specimen at their initial consultation, a specimen collected at home the next morning, and a second on-the-spot sample when they deliver their morning specimen. In the spot-spot-morning (SSM) scheme, patients provide two on-the-spot samples during their first clinic visit and a sample collected at home the next morning. What Did the Researchers Do and Find? In the main trial, the researchers collected sputum samples using the SMS or SSM scheme from 6,627 patients with a cough lasting more than two weeks. For their investigation of LED-FM, they examined nearly 2,400 samples (half SSM and half SMS specimens, about a quarter of which were tuberculosis culture-positive) with both ZN smear microscopy and LED-FM and determined the sensitivity and specificity of both tests—with one, two, or three sputum samples per patient—relative to mycobacterial solid culture. Single LED-FM smears had higher sensitivity but lower specificity than single ZN smears. The sensitivities of two LED-FM and two ZN smears were 72.8% and 65.8%, respectively; the specificities of these tests were 90.9% and 98.0%. The sensitivities of three LED-FM and three ZN smears were 77% and 70.5%, respectively; the specificities of these tests were 88.1% and 96.5%. The sensitivity and specificity of both tests was similar for samples collected using the SMS and the SSM schemes. What Do These Findings Mean? These findings show that in the resource-limited countries included in this trial, LED-FM has a higher sensitivity but lower specificity than ZN smear microscopy. The researchers calculate that in this study the accuracy of three LED-FM examinations was 85% (2,017 out of 2,355 patients were correctly classified as infected or uninfected), whereas the accuracy of three ZN smears was 91.8%. Thus, although LED-FM should identify more people with tuberculosis than ZN smear microscopy, because of its lower specificity, its use might also lead to more people without tuberculosis being needlessly treated for the disease. Nevertheless, provided that the introduction of LED-FM is accompanied by appropriate training and performance monitoring, LED-FM is an attractive potential tool for the laboratory diagnosis of tuberculosis that, together with a move towards the collection of two on-the-spot smears in a single clinic visit, could ensure that poor patients have access to timely tuberculosis diagnosis and prompt treatment. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001057. Details of the parent trial in which the samples used in this study were collected are available in a PLoS Medicine Research Article by Cuevas et al. The World Health Organization provides information on all aspects of tuberculosis, including information on tuberculosis diagnostics; recent WHO policy statements on diagnosis of tuberculosis are available; the Stop TB Partnership provides information on global tuberculosis control (some information in several languages) The US Centers for Disease Control and Prevention has information about tuberculosis, including information on the diagnosis of tuberculosis disease The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis MedlinePlus has links to further information about tuberculosis (in English and Spanish) A new Web site dedicated to the discussion and optimization of smear microscopy has recently been launched

Background: Nucleic acid amplification tests (NAAT) based on PCR provide rapid identification of Mycobacterium tuberculosis and the detection of rifampicin resistance. Indications for their use in clinical samples are now included in British tuberculosis guidelines. Methods: A retrospective audit of patients with suspected mycobacterial infection in a Liverpool hospital between 2002 and 2006. Documentation of the impact of NAAT usage in acid fast bacillus (AFB) microscopy positive samples on clinical practice and the influence of a multidisciplinary group on their appropriate use, compared with British guidelines. Results: Mycobacteria were seen or isolated from 282 patients and identified as M tuberculosis in 181 (64%). NAAT were indicated in 87/123 AFB positive samples and performed in 51 (59%). M tuberculosis was confirmed or excluded by this method in 86% of tested samples within 2 weeks, compared with 7% identified using standard methods. The appropriate use of NAAT increased significantly over the study period. The NAAT result had a clinical impact in 20/51 (39%) tested patients. Culture results suggest the potential for a direct clinical impact in 8/36 (22%) patients in which it was indicated but not sent and 5/36 (14%) patients for whom it was not indicated. Patients managed by the multidisciplinary group had a higher rate of HIV testing and appropriate use of NAAT. Conclusions: There were significant clinical benefits from the use of nucleic acid amplification tests in this low prevalence setting. Our data suggest that there would be additional benefit from their use with all AFB smear positive clinical samples.

We describe the performance of bleach-digested Zeihl-Neelsen (ZN) smears in TB suspects with/without HIV. In total, 51 (26%) and 62 (31%) out of the first 198 spot and digested smears were positive. Seven of the 30 HIV-positive patients had TB and their ZN smears were negative, scanty or 1 +. Six of seven digested smears were scanty. Forty-two of 115 HIV-negative patients had TB. Eleven (26%) of their digested smears were negative, 12 (29%) scanty and 19 (45%) positive. Despite the lower bacilli numbers of HIV-positive patients, the technique had sensitivity and specificity similar to that in HIV-negative patients.

The bleach digestion of sputum may improve the yield of smear microscopy but has not been validated in patients with HIV. Therefore we assessed the performance of bleach-digested smear microscopy among patients with HIV. One thousand three hundred and twenty one patients with chronic cough submitted three sputum samples for direct smear microscopy and were offered HIV tests. One sample was selected for a bleach-digested smear and another one was cultured. Patients were classified as having 'definite' (>= 2 positive smears), 'very likely' (smear-negative, culture- positive), 'less likely' (one smear-positive, culture-negative) and 'unlikely' (smear and culture negative) tuberculosis (TB). In all, 566/1045 (54%) patients were HIV positive and 731/1186 (62%) were culture positive. The digested smears were positive in 123/125 (98%) 'definite', 4/118 (3%) 'very likely' and 1/174 'unlikely' TB patients with HIV and in 125/127 (98%) 'definite', 2/74 (3%) 'very likely', 4/4 'less likely' and 2/127 'unlikely' TB without HIV. Three direct smears identified 252 (57%) and one digested smear 254 (57%) of the 444 patients with 'definite' or 'very likely' TB. One bleach-digested smear performed similarly to three direct smears. Both methods were less sensitive in HIV-positive patients. Further studies are needed to compare the performance of the two methods under operational conditions. (c) 2007 Elsevier Ltd. All rights reserved.

China has made a significant achievement in tackling the TB epidemic over the last decade, due largely to the implementation of directly-observed treatment strategy (DOT). The cure rate of TB cases reached more than 90% for registered TB patients. However, the case detection rate has, unfortunately, been very low (some 30%). Using available information, this paper identifies four main problems facing TB control in China, these are, low case finding, a substantial proportion of TB patients failing to complete standardised treatment, increased proportion of MDR TB patients, and lack of effective TB control among "floating populations". The paper also analyses the possible causes of these problems associated with socio-economic barriers in care seeking, ineffectiveness of TB services, particularly in poor areas, lack of co-operation between health facilities, and weakness of political and financial commitments of local governments to TB control. The paper ends with the discussion of opportunities and challenges facing TB control and makes recommendations for further actions and research.

Summary Background Smear microscopy is relatively insensitive for the diagnosis of TB. The digestion of sputum with household bleach prior to smear preparation has been reported to improve its sensitivity. This method has not been validated. Methods Seven hundred and fifty six patients with symptoms suggestive of pulmonary TB (PTB) were asked to submit 3 sputum specimens for direct microscopy. One specimen was selected at random for culture and another specimen was digested to prepare a further smear. The WHO case definition (⩾2 positive smears or one positive smear and positive culture) was used to compare the sensitivity and specificity of the smears. Findings Four hundred and fifty five (60%) patients were culture-positive. Of these, 235 (31%) had “definite” PTB and 223 (29%) “very likely” PTB (smear-negative, culture-positive). The WHO case definition identified 51% (235/458) of the patients with “definite” or “very likely” PTB. One digested smear detected 219 (93%) of the 235 patients with “definite” PTB and 10 patients with “very likely” PTB (sensitivity (95%CI) 50% (45–55%); specificity 99% (97–100%)). The positive and negative predictive values for one digested smear were 98% (95–99%) and 56% (52–60%) respectively, which were not different ( p > 0.5 ) to the WHO case definition (100% and 57%, respectively). Interpretation One bleach-digested smear is as sensitive and specific as the WHO case definition for the diagnosis of PTB.

BACKGROUND: The number of people infected with tuberculosis continues to rise worldwide. Rifampicin‐containing treatment regimens can achieve high cure rates. Intermittent drug treatment delivered in the community has the potential to improve adherence to treatment. OBJECTIVES: The objective of this review was to compare the effectiveness of rifampicin‐containing short‐course chemotherapy regimens, given two or three times a week, with similar regimens given daily in adult patients with pulmonary tuberculosis. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group specialized trials register (January 2003), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2002), MEDLINE (1966 to January 2003), EMBASE (1980 to December 2002), and reference lists of articles. We contacted experts in the field. SELECTION CRITERIA: Randomized and quasi‐randomized trials of any multiple drug regimen containing rifampicin in patients with confirmed pulmonary tuberculosis. Treatment had to be given up to three times a week for up to nine months, with any initial daily dosing period not more than one month, and was compared to daily dosing throughout for the same period. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality. MAIN RESULTS: One trial involving 399 patients was included. The trial compared treatment three times per week with daily treatment for six months. There was no difference in cure rate (198 out of 199 people in the intermittent group compared to all 200 in the daily group), but 5 patients relapsed in the group receiving intermittent therapy compared to one in the group receiving the daily regimen. AUTHORS' CONCLUSIONS: There is not enough evidence to assess the equivalence of effect between fully intermittent, rifampicin‐containing short‐course chemotherapy and similar daily therapy in patients with pulmonary tuberculosis. Larger randomized studies are required to establish the equivalence of fully intermittent, short‐course chemotherapy, with daily regimens.

Contains fulltext : 96579.pdf (Publisher’s version ) (Open Access) BACKGROUND: More than 50 million people around the world are investigated for tuberculosis using sputum smear microscopy annually. This process requires repeated visits and patients often drop out. METHODS AND FINDINGS: This clinical trial of adults with cough >/=2 wk duration (in Ethiopia, Nepal, Nigeria, and Yemen) compared the sensitivity/specificity of two sputum samples collected "on the spot" during the first visit plus one sputum sample collected the following morning (spot-spot-morning [SSM]) versus the standard spot-morning-spot (SMS) scheme. Analyses were per protocol analysis (PPA) and intention to treat (ITT). A sub-analysis compared just the first two smears of each scheme, spot-spot and spot-morning. In total, 6,627 patients (3,052 SSM/3,575 SMS) were enrolled; 6,466 had culture and 1,526 were culture-positive. The sensitivity of SSM (ITT, 70.2%, 95% CI 66.5%-73.9%) was non-inferior to the sensitivity of SMS (PPA, 65.9%, 95% CI 62.3%-69.5%). Similarly, the specificity of SSM (ITT, 96.9%, 95% CI 93.2%-99.9%) was non-inferior to the specificity of SMS (ITT, 97.6%, 95% CI 94.0%-99.9%). The sensitivity of spot-spot (ITT, 63.6%, 95% CI 59.7%-67.5%) was also non-inferior to spot-morning (ITT, 64.8%, 95% CI 61.3%-68.3%), as the difference was within the selected -5% non-inferiority limit (difference ITT = 1.4%, 95% CI -3.7% to 6.6%). Patients screened using the SSM scheme were more likely to provide the first two specimens than patients screened with the SMS scheme (98% versus 94.2%, p

World wide, more adult deaths are attributed to Mycobacterium tuberculosis than to any other infectious agent, and without improvements in control 30 million people are expected to die from tuberculosis in 1990-2000.1 In sub-Saharan Africa alone about 1.5 million new cases arise each year. How can we care for all these patients? We have known for almost 40 years that most patients with tuberculosis can be treated in the community without increasing the risk of their infecting contacts. Indeed, the strategy of supervised outpatient therapy was developed in poor settings.2 Nevertheless, until recently, the World Health Organisation and the International Union Against Tuberculosis and Lung Disease advocated a strategy of admission to hospital for at least the first two months of treatment, primarily as a way of ensuring adherence. Indeed hospitalisation, together with the other elements of the control programme, was highly effective.3 However, the epidemic of tuberculosis associated with HIV in sub-Saharan Africa is such that hospital based care is no longer feasible. The caseload in Malawi increased from 5334 in 1985 to 19 195 in 1995 (Malawi …

Objective: To determine whether preventive treatment for tuberculosis in adults infected with HIV reduces the frequency of tuberculosis and overall mortality. Design: Systematic review and data synthesis of randomised placebo controlled trials. Main outcome measures: Active tuberculosis, mortality, and adverse drug reaction requiring cessation of the study regimen. Outcomes stratified by status of purified protein derivative skin test. Results: Four trials comprising 4055 adults from Haiti, Kenya, the United States, and Uganda were included. All compared isoniazid (6-12 months) with placebo, and one trial also compared multidrug treatment for 3 months with placebo. Mean follow up was 15-33 months. Overall, frequency of tuberculosis (relative risk 0.57, 95% confidence interval 0.41 to 0.79) was reduced in those receiving preventive treatment compared with placebo: mortality was not significantly reduced (0.93, 0.83 to 1.05). In subjects positive for purified protein derivative receiving preventive treatment, the risk of tuberculosis was reduced substantially (0.32, 0.19 to 0.51) and the risk of death was reduced moderately (0.73, 0.57 to 0.95) compared with those taking placebo. In adults negative for purified protein derivative receiving preventive treatment, the risk of tuberculosis (0.82, 0.50 to 1.36) and the risk of death (1.02, 0.89 to 1.17) were not reduced significantly. Adverse drug reactions were more frequent, but not significantly so, in patients receiving drug compared with placebo (1.45, 0.98 to 2.14). Conclusions: Preventive treatment given for 3-12 months protects against tuberculosis in adults infected with HIV, at least in the short to medium term. Protection is greatest in subjects positive for purified protein derivative, in whom death is also less frequent. Long term benefits remain to be shown.