Potential cost-effectiveness of rifampin vs. isoniazid for latent tuberculosis: implications for future clinical trials.

SETTING: Standard treatment for latent tuberculosis infection (LTBI) is 9 months daily isoniazid (9INH). An alternative is 4 months daily rifampin (4RMP), associated with better completion and less toxicity; however, its efficacy remains uncertain. OBJECTIVES: To assess the cost-effectiveness of these regimens for treating LTBI in human immunodeficiency virus negative persons, using results from a recent clinical trial, plus different scenarios for 4RMP efficacy, and to estimate the costs of an adequately powered noninferiority trial and resulting savings from substitution with 4RMP. DESIGN: A decision-analysis model tracked TB contacts and lower-risk tuberculin reactors receiving 9INH, 4RMP or no treatment. For different 4RMP efficacy scenarios, we estimated the cost-effectiveness, sample size and cost of non-inferiority trials, and potential cost savings substituting 4RMP for 9INH for 10 years in Canada. RESULTS: With an assumed 4RMP efficacy of 60%, 9INH was more effective but slightly more expensive. Above a threshold efficacy of 69%, 4RMP was cheaper and more effective than 9INH. If the true efficacy of 4RMP is ≥75%, a trial powered to detect non-inferiority with a lower limit of 60% estimated efficacy (~20 000 subjects) may lead to cost savings within 10 years, even with the extreme assumption that Canada bears the entire cost. CONCLUSION: 4RMP may be a reasonable alternative to 9INH. Costs of a large-scale non-inferiority trial may be offset by subsequent savings.

Cost of tuberculosis diagnosis and treatment from the patient perspective in Lusaka, Zambia.

SETTING: Urban primary health centres in Lusaka, Zambia. OBJECTIVES: 1) To estimate patient costs for tuberculosis (TB) diagnosis and treatment and 2) to identify determinants of patient costs. METHODS: A cross-sectional survey of 103 adult TB patients who had been on treatment for 1-3 months was conducted using a standardised questionnaire. Direct and indirect costs were estimated, converted into US$ and categorised into two time periods: 'pre-diagnosis/care-seeking' and 'post-diagnosis/treatment'. Determinants of patient costs were analysed using multiple linear regression. RESULTS: The median total patient costs for diagnosis and 2 months of treatment was $24.78 (interquartile range 13.56-40.30) per patient--equivalent to 47.8% of patients' median monthly income. Sex, patient delays in seeking care and method of treatment supervision were significant predictors of total patient costs. The total direct costs as a proportion of income were higher for women than men (P < 0.001). Treatment costs incurred by patients on the clinic-based directly observed treatment strategy were more than three times greater than those incurred by patients on the self-administered treatment strategy (P < 0.001). CONCLUSION: Clinic-based treatment supervision posed a significant economic burden on patients. The creation or strengthening of community-based treatment supervision programmes would have the greatest potential impact on reducing patients' TB-related costs.

Clinical heterogeneity and prognosis in combined methylmalonic aciduria and homocystinuria (cblC).

The clbC form of methylmalonic acidaemia is a rare and poorly understood condition which results from impaired biosynthesis of methylcobalamin and adenosylcobalamin. The consequent functional deficiencies of methylmalonyl-CoA mutase and methionine synthase produce both methylmalonic aciduria and homocystinuria. Systemic symptoms and neurological decompensation comprise the clinical phenotype. In an effort to clarify the phenotype and prognosis, we obtained clinical information on 50 patients with methylmalonic acidaemia whose cells had been assigned to the cblC complementation group. We identified two distinct phenotypes; they differed in age of onset, presence of systemic symptoms, type of neurological symptoms, and outcome after diagnosis and treatment. Forty-four patients presented in the first year of life. Feeding difficulties, neurological dysfunction (hypotonia, seizures, developmental delay), and ophthalmological and haematological abnormalities characterized their clinical picture. About one-quarter of those patients died. Survival was associated with neurological impairment; only one infant was neurologically intact at follow-up. Onset in childhood, in contrast, was associated with less severe haematological abnormalities, largely involving the red cell series. Extrapyramidal signs, dementia, delirium or psychosis characterized the neurological findings. Survival, with mild to moderate disability in some, was typical in patients with later onset. Treatment in both groups included hydroxycobalamin, betaine and carnitine; complete normalization of biochemical parameters was rare.