Journal Article > ResearchFull Text
PLOS Med. 1 October 2006; Volume 3 (Issue 10); DOI:10.1371/journal.pmed.0030384
Cox HS, Kebede YYK, Allamuratova S, Ismailov G, Davletmuratova Z, et al.
PLOS Med. 1 October 2006; Volume 3 (Issue 10); DOI:10.1371/journal.pmed.0030384
BACKGROUND: The DOTS (directly observed treatment short-course) strategy for tuberculosis (TB) control is recommended by the World Health Organization globally. However, there are few studies of long-term TB treatment outcomes from DOTS programs in high-burden settings and particularly settings of high drug resistance. A DOTS program was implemented progressively in Karakalpakstan, Uzbekistan starting in 1998. The total case notification rate in 2003 was 462/100,000, and a drug resistance survey found multidrug-resistant (MDR) Mycobacterium tuberculosis strains among 13% of new and 40% of previously treated patients. A retrospective, observational study was conducted to assess the capacity of standardized short-course chemotherapy to effectively cure patients with TB in this setting. METHODS AND FINDINGS: Using routine data sources, 213 patients who were sputum smear-positive for TB, included in the drug resistance survey and diagnosed consecutively in 2001-2002 from four districts, were followed up to a median of 22 months from diagnosis, to determine mortality and subsequent TB rediagnosis. Valid follow-up data were obtained for 197 (92%) of these patients. Mortality was high, with an average of 15% (95% confidence interval, 11% to 19%) dying per year after diagnosis (6% of 73 pansusceptible cases and 43% of 55 MDR TB cases also died per year). While 73 (74%) of the 99 new cases were "successfully" treated, 25 (34%) of these patients were subsequently rediagnosed with recurrent TB (13 were smear-positive on rediagnosis). Recurrence ranged from ten (23%) of 43 new, pansusceptible cases to six (60%) of ten previously treated MDR TB cases. MDR M. tuberculosis infection and previous TB treatment predicted unsuccessful DOTS treatment, while initial drug resistance contributed substantially to both mortality and disease recurrence after successful DOTS treatment. CONCLUSIONS: These results suggest that specific treatment of drug-resistant TB is needed in similar settings of high drug resistance. High disease recurrence after successful treatment, even for drug-susceptible cases, suggests that at least in this setting, end-of-treatment outcomes may not reflect the longer-term status of patients, with consequent negative impacts for patients and for TB control.
Journal Article > ResearchFull Text
Trop Med Int Health. 1 June 1996; Volume 1 (Issue 3); 385-392.; DOI:10.1046/j.1365-3156.1996.d01-49.x
Haelterman E, Boelaert M, Suetens C, Blok L, Henkens M, et al.
Trop Med Int Health. 1 June 1996; Volume 1 (Issue 3); 385-392.; DOI:10.1046/j.1365-3156.1996.d01-49.x
Serogroup A meningococcus epidemics occurred in refugee populations in Zaire in August 1994. The paper analyses the public health impact of a mass vaccination campaign implemented in a large refugee camp. We compared meningitis incidence rates from 2 similar camps. In Kibumba camp, vaccination was implemented early in the course of the epidemic whilst in the control camp (Katale), vaccination was delayed. At a threshold of 15 cases per 100 000 population per week an immunization campaign was implemented. Attack rates were 94 and 134 per 100,000 in Kibumba and Katale respectively over 2 months. In Kibumba, one week after crossing the threshold, 121,588 doses of vaccine were administered covering 76% of all refugees. Vaccination may have prevented 68 cases (30% of the expected cases). Despite its rapid institution and the high coverage achieved, the vaccination campaign had a limited impact on morbidity due to meningitis. In the early phase in refugee camps, the relative priorities of meningitis vaccination and case management need to be better defined.
Journal Article > ResearchFull Text
Clin Infect Dis. 1 June 2007; Volume 44 (Issue 11); DOI:10.1086/517536
Cox HS, Niemann S, Ismailov G, Doshetov D, Orozco JD , et al.
Clin Infect Dis. 1 June 2007; Volume 44 (Issue 11); DOI:10.1086/517536
BACKGROUND: Data on the performance of standardized short-course directly observed treatment (DOTS) of tuberculosis (TB) in areas with high levels of drug resistance and on the potential impact of DOTS on amplification of resistance are limited. Therefore, we analyzed treatment results from a cross-sectional sample of patients with TB enrolled in a DOTS program in an area with high levels of drug resistance in Uzbekistan and Turkmenistan in Central Asia. METHODS: Sputum samples for testing for susceptibility to 5 first-line drugs and for molecular typing were obtained from patients starting treatment in 8 districts. Patients with sputum smear results positive for TB at the end of the intensive phase of treatment and/or at 2 months into the continuation phase were tested again. RESULTS. Among 382 patients with diagnoses of TB, 62 did not respond well to treatment and were found to be infected with an identical Mycobacterium tuberculosis strain when tested again; 19 of these patients had strains that developed new or additional drug resistance. Amplification occurred in only 1.2% of patients with initially susceptible or monoresistant TB strains, but it occurred in 17% of those with polyresistant strains (but not multidrug-resistant strains, defined as strains with resistance to at least isoniazid and rifampicin) and in 7% of those with multidrug-resistant strains at diagnosis. Overall, 3.5% of the patients not initially infected with multidrug-resistant TB strains developed such strains during treatment. Amplification of resistance, however, was found only in polyresistant Beijing genotype strains. CONCLUSIONS: High levels of amplification of drug resistance demonstrated under well-established DOTS program conditions reinforce the need for implementation of DOTS-Plus for multidrug-resistant TB in areas with high levels of drug resistance. The strong association of Beijing genotype and amplification in situations of preexisting resistance is striking and may underlie the strong association between this genotype and drug resistance.