Analysis of latent tuberculosis and mycobacterium avium infection data using mixture models

BACKGROUND: Estimation of the frequency of latent tuberculosis infection (LTBI) is difficult in areas with low tuberculosis infection rates and high exposure to non-tuberculous mycobacteria (NTM), including BCG vaccination. The objective was to assess LTBI and M avium infection and to estimate their probability based on skin tests responses in an infant population from a region with the aforementioned characteristics. METHODS: A population-based tuberculin skin test (TST) and sensitin (M avium) survey was conducted on seven years old infants in Biscay, a province from The Basque Country (Spain). 2268 schoolchildren received sensitin and 5277 TST. Participation rate was 89%. Commonly used estimation methods were compared with a method based on the fit of mixture models using the Expectation Maximization algorithm. Functions estimating the probabilities of LTBI and M avium infection given the observed skin tests responses were developed for vaccinated and unvaccinated children. RESULTS: LTBI prevalences varied widely according to the estimation method. The mixture model provided prevalences higher than expected although intermediates between those obtained by currently recommended approaches. Exposure to previous BCG vaccine produces an upward shift of an average of about 3 mm on the induration size to attain the same probability of infection. CONCLUSION: Our results confirm the commonplace exposure to NTM which effect should be taken into account when performing and assessing tuberculin surveys. The use of mixture analysis under the empirical Bayes framework allows to better estimate the probability of LTBI in settings with presence of other NTM and high BCG-vaccination coverage. An estimation of the average effect of BCG vaccination on TST induration is also provided. These models maximise information coming from classical tuberculin surveys and could be used together with the newly developed blood tests to improve survey's specificity and cost-effectiveness

What 'outliers' tell us about missed opportunities for tuberculosis control: a cross-sectional study of patients in Mumbai, India

BACKGROUND: India's Revised National Tuberculosis Control Programme (RNTCP) is deemed highly successful in terms of detection and cure rates. However, some patients experience delays in accessing diagnosis and treatment. Patients falling between the 96th and 100th percentiles for these access indicators are often ignored as atypical 'outliers' when assessing programme performance. They may, however, provide clues to understanding why some patients never reach the programme. This paper examines the underlying vulnerabilities of patients with extreme values for delays in accessing the RNTCP in Mumbai city, India. METHODS: We conducted a cross-sectional study with 266 new sputum positive patients registered with the RNTCP in Mumbai. Patients were classified as 'outliers' if patient, provider and system delays were beyond the 95th percentile for the respective variable. Case profiles of 'outliers' for patient, provider and system delays were examined and compared with the rest of the sample to identify key factors responsible for delays. RESULTS: Forty-two patients were 'outliers' on one or more of the delay variables. All 'outliers' had a significantly lower per capita income than the remaining sample. The lack of economic resources was compounded by social, structural and environmental vulnerabilities. Longer patient delays were related to patients' perception of symptoms as non-serious. Provider delays were incurred as a result of private providers' failure to respond to tuberculosis in a timely manner. Diagnostic and treatment delays were minimal, however, analysis of the 'outliers' revealed the importance of social support in enabling access to the programme. CONCLUSION: A proxy for those who fail to reach the programme, these case profiles highlight unique vulnerabilities that need innovative approaches by the RNTCP. The focus on 'outliers' provides a less resource- and time-intensive alternative to community-based studies for understanding the barriers to reaching public health programmes

Management and outcome of tuberculosis patients who fail treatment under routine programme conditions in Malawi.

SETTING: All 43 non-private hospitals (three central, 22 district and 18 mission) in Malawi that registered and treated TB cases between 1 July 1999 and 30 June 2000. OBJECTIVES: To determine 1) the number of new smear-positive PTB patients who failed treatment, 2) the management of patients who failed, 3) their treatment outcome and 4) culture and drug sensitivity results. DESIGN: Retrospective data collection using TB registers and laboratory culture and drug sensitivity registers. RESULTS: Ninety patients failed treatment, 60 (67%) at 5 months and 30 (33%) at the end of treatment. Sixty-four (71%) failure patients were registered and commenced on anti-tuberculosis treatment. Of these, 95% were registered in the same hospital as before, 89% were given a different TB registration number, 67% were correctly registered as 'failures' and 61% were treated within one month of failing the previous regimen. Forty-eight (75%) re-treated patients were cured. Only 31 (34%) of the 90 patients had sputum sent for culture and drug sensitivity testing. In 11 patients with cultures of M. tuberculosis, eight were fully sensitive and three had mono-resistance to isoniazid. CONCLUSION: While the outcome of failure patients who start retreatment is good, there are several programmatic deficiencies that need to be corrected

Decentralisation of tuberculosis services in an urban setting, Lilongwe, Malawi.

SETTING: Lilongwe, the capital of Malawi, one of the countries in the world badly affected by the human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) epidemic. OBJECTIVE: In the face of a rising burden of tuberculosis (TB) fuelled by HIV, to evaluate the impact on the Lilongwe district tuberculosis programme performance of decentralisation of TB services, including extending the range of options for supervision of directly observed treatment (DOT) during the initial phase of treatment, and using a fully oral, intermittent regimen. DESIGN: Prospective assessment under programme conditions of 1) duration of hospital stay, 2) bed occupancy and 3) 8-month treatment outcomes in a cohort of patients registered before (1997) and after (1998) the introduction of decentralisation of TB services. RESULTS: The number of new patients (all forms) registered in Lilongwe district was 3144 in 1997 and 3761 in 1998. There were significant differences (P < 0.05) between all outcomes that were compared. In 1998, bed occupancy dropped by 38%; among smear-positive patients, the average length of hospital stay fell from 58 days in 1997 to 16, the cure rate was higher (64% vs. 56%), default rate was lower (5% vs. 19%), and treatment completion rate was lower (2% vs. 4%); among smear-negative patients, the treatment completion rate was higher (50% vs. 33%), default rate was lower (23% vs. 55%), and death rate was higher (17% vs. 4%). This death rate is attributable to improved follow-up and reporting of outcomes, rather than to increased deaths. CONCLUSION: Programme implementation of decentralised TB services in Lilongwe, including an extended range of supervision options for DOT and the use of an ambulatory treatment regimen, achieved reduced hospital stay and bed occupancy and good treatment outcomes

Can we get more HIV-positive tuberculosis patients on antiretroviral treatment in a rural district of Malawi?

The World Health Organization (WHO) has set a target of treating 3 million people with antiretroviral treatment (ART) by 2005. In sub-Saharan Africa, HIV-positive tuberculosis (TB) patients could significantly contribute to this target. ART (stavudine/lamivudine/nevirapine) was initiated in Thyolo district, Malawi, in April 2003, and all HIV-positive TB patients were considered eligible and offered ART. Despite this, only 44 (13%) of 352 TB patients were eventually started on ART by the end of November 2003. Most TB patients leave hospital after 2 weeks to complete the initial phase of anti-tuberculosis treatment (rifampicin-based) in the community, and ART is offered to HIV-positive TB patients after they have started the continuation phase of treatment (isoniazid/ ethambutol). ART is only offered at hospital, while the majority of TB patients take their continuation phase of anti-tuberculosis treatment from health centres. HIV-positive TB patients therefore find it difficult to access ART. In this paper, we discuss a series of options to increase the uptake of ART among HIV-positive TB patients. The main options are: 1) to hospitalise HIV-positive TB patients with a view to starting ART in the continuation phase in hospital; 2) to decentralise ART delivery so ART can be delivered at health centres; 3) to replace nevirapine with efavirenz so ART can be started earlier in the initial phase of anti-tuberculosis treatment. Decentralisation of ART from hospitals to health centres would greatly improve ART access

Long-term outcome in patients registered with tuberculosis in Zomba, Malawi: mortality at 7 years according to initial HIV status and type of TB.

SETTING: Zomba Central Hospital, Malawi. OBJECTIVES: To determine the outcome of all adult patients who were registered for tuberculosis (TB) treatment 7 years previously according to initial human immunodeficiency virus (HIV) status and type of TB. DESIGN: A retrospective cohort study of adult patients registered for TB treatment between July and December 1995. Follow-up at patients' homes was performed at the end of treatment, at 32 months and at 84 months (7 years) from the time of TB registration. FINDINGS: Eight hundred and twenty-seven TB patients were registered: 793 had concordant HIV test results, of whom 612 (77%) were HIV-positive. At 7 years, 136 (17%) patients were alive, 539 (65%) had died and 152 (18%) were lost to follow-up. The death rate for all TB patients was 23.7 per 100 person-years of observation. HIV-positive patients had higher death rates than HIV-negative patients (hazard ratio [HR] 2.2, 95% confidence interval [95%CI] 1.7-2.8). Death rates in smear-negative pulmonary TB patients (HR 2.1, 95%CI 1.7-2.6) and in patients with extra-pulmonary TB (HR 1.7, 95% CI 1.3-2.0) were higher than in patients with smear-positive PTB. CONCLUSIONS: There was a high mortality rate in TB patients during and after anti-tuberculosis treatment. Adjunctive treatments to reduce death rates are urgently needed