Improving tuberculosis control: an interdisciplinary approach.
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Biomedical subjects
Publications and source records attributed to Roxana Rustomjee.
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Over recent years, tuberculosis (TB) and disease caused by human immunodeficiency virus (HIV) have merged in a synergistic pandemic. The number of new cases of TB is stabilizing and declining, except in countries with a high prevalence of HIV infection. In these countries, where HIV is driving an increase in the TB burden, the capacity of the current tools and strategies to reduce the burden has been exceeded. This paper summarizes the current status of TB management and describes recent thinking and strategy adjustments required for the control of TB in settings of high HIV prevalence. We review the information on anti-TB drugs that is available in the public domain and highlight the need for continued and concerted efforts (including financial, human and infrastructural investments) for the development of new strategies and anti-TB agents.
RATIONALE: Comparison of the early bactericidal activity (EBA) of rifapentine and its pharmacokinetics with those of rifampin to determine the cause of poor clinical response and regrowth between doses, leading to rifamycin monoresistance at relapse. OBJECTIVES: Determination of the dose size of rifapentine that gives sufficient drug exposure to prevent regrowth. METHODS: EBA study over initial 5 days of treatment of 123 patients, half at Durban and half at Cape Town, who received single rifapentine doses of 300, 600, 900, or 1,200 mg rifapentine or five daily doses of 150, 300, or 600 mg rifampin, with a pharmacokinetic study on 58 patients measuring standard parameters for each dose size of rifamycin and their desacetyl metabolites. RESULTS: The EBAs for both rifamycins were similar, with a linear relationship to log dose at lower doses and a curvilinear response at higher doses giving a plateau at 1,136 mg rifapentine. The area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) agreed well for both rifamycins on the assumption that the only free 2% of free rifapentine and the 14% of free rifampin after plasma binding were active in the lesions. CONCLUSIONS: Only the free proportions of the rifamycins were active in lesions. From consideration of the pulse size and the duration of the postantibiotic lag, a 1,200-mg dose of rifapentine seemed necessary to improve response and to prevent regrowth between doses, and hence rifamycin monoresistance.
A randomized controlled trial was carried out to assess the effectiveness of azithromycin versus a standard regimen with doxycycline/ciprofloxacin in the treatment of sexually transmitted infections in a resource-poor environment. Infection with Chlamydia trachomatis was cured in 23/24 (95.8%) of women in the azithromycin arm versus 19/21 (90.5%) in the doxycycline arm (P = 0.6), resulting in three treatment failures. Gonorrhoea was cured in 55/56 (98.2%) women, with one treatment failure in a patient with concomitant C. trachomatis infection. These results indicate that a single oral dose of azithromycin may prove to be a more effective and convenient treatment for sexually transmitted infections in women in a resource-poor environment