Ambulatory-based standardized therapy for multi-drug resistant tuberculosis: experience from Nepal, 2005-2006.

OBJECTIVE: The aim of this study was to describe treatment outcomes for multi-drug resistant tuberculosis (MDR-TB) outpatients on a standardized regimen in Nepal. METHODOLOGY: Data on pulmonary MDR-TB patients enrolled for treatment in the Green Light Committee-approved National Programme between 15 September 2005 and 15 September 2006 were studied. Standardized regimen was used (8Z-Km-Ofx-Eto-Cs/16Z-Ofx-Eto-Cs) for a maximum of 32 months and follow-up was by smear and culture. Drug susceptibility testing (DST) results were not used to modify the treatment regimen. MDR-TB therapy was delivered in outpatient facilities for the whole course of treatment. Multivariable analysis was used to explain bacteriological cure as a function of sex, age, initial body weight, history of previous treatment and the region of report. PRINCIPAL FINDINGS: In the first 12-months, 175 laboratory-confirmed MDR-TB cases (62% males) had outcomes reported. Most cases had failed a Category 2 first-line regimen (87%) or a Category 1 regimen (6%), 2% were previously untreated contacts of MDR-TB cases and 5% were unspecified. Cure was reported among 70% of patients (range 38%-93% by Region), 8% died, 5% failed treatment, and 17% defaulted. Unfavorable outcomes were not correlated to the number of resistant drugs at baseline DST. Cases who died had a lower mean body weight than those surviving (40.3 kg vs 47.2 kg, p<0.05). Default was significantly higher in two regions [Eastern OR = 6.2; 95%CL2.0-18.9; Far West OR = 5.0; 95%CL1.0-24.3]. At logistic regression, cure was inversely associated with body weight <36 kg [Adj.OR = 0.1; 95%CL0.0-0.3; ref. 55-75 kg] and treatment in the Eastern region [Adj.OR = 0.1; 95%CL0.0-0.4; ref. Central region]. CONCLUSIONS: The implementation of an ambulatory-based treatment programme for MDR-TB based on a fully standardized regimen can yield high cure rates even in resource-limited settings. The determinants of unfavorable outcome should be investigated thoroughly to maximize likelihood of successful treatment.

Delay in the diagnosis of tuberculosis in Nepal.

BACKGROUND: Identifying reasons for delay in diagnosis and treatment of tuberculosis is important for the health system to find ways to treat patients as early as possible, and hence reduce the suffering of patients and transmission of the disease. The objectives of this study was to assess the duration of delay in the diagnosis of tuberculosis and to investigate its determinants. METHODS: A cross-sectional survey was conducted using a structured questionnaire in 307 new tuberculosis patients registered by the National Tuberculosis Programme (NTP) in all DOTS centres in Banke district of Nepal. RESULTS: The median patient delay was 50 days, the median health system delay was 18 days, and the median total delay was 60 days. Sputum smear negative participants had significantly lower risk of patient delay. Smokers using >5 cigarettes per day had higher risk of patient delay and health system delay. CONCLUSION: Total delay in the diagnosis of tuberculosis in Banke district is shorter compared to other places in Nepal and neighbouring countries. The shorter delay for smear negative pulmonary tuberculosis raises suspicion that many of these patients are not examined according to the NTP manual before being diagnosed. Increasing public awareness of the disease and expansion of the facilities with assured quality could be helpful to reduce the delay in the diagnosis of tuberculosis.

Family-member DOTS and community DOTS for tuberculosis control in Nepal: cluster-randomised controlled trial.

BACKGROUND: A key component of the DOTS strategy for tuberculosis control (short-course chemotherapy following WHO guidelines) is direct observation of treatment. WHO technical guidelines recommend that health workers should undertake this part of the strategy, but will also accept direct observation of treatment in the community; WHO does not think that a family member should undertake this role. Supporting evidence for these recommendations is not available. The Nepal national tuberculosis programme asked us to develop and test a strategy of direct observation of treatment for the hill districts of Nepal, where direct observation of treatment by health workers is not feasible. We aimed to assess the success rates of two DOTS strategies developed for such areas. METHODS: Between mid-July, 2002, and mid-July, 2003, we undertook a cluster-randomised controlled trial to compare two strategies-community DOTS and family-member DOTS--in ten hill and mountain districts of Nepal. Districts were used as the unit of randomisation. Primary outcome was success rate (proportion of registered patients who achieved cure or completed treatment), and analysis was by intention to treat. FINDINGS: Five districts (549 patients) were allocated to community DOTS and five (358 patients) were allocated family-member DOTS. Community DOTS and family-member DOTS achieved success rates of 85% and 89%, respectively (odds ratio of success for community DOTS relative to family-member DOTS, 0.67 [95% CI 0.41-1.10]; p=0.09). Estimated case-finding rates were 63% with the community strategy and 44% with family-member DOTS. INTERPRETATION: The family-member DOTS and community DOTS strategies can both attain international targets for treatment success under programme conditions, and thus are appropriate for the hill and mountain districts of Nepal. Both strategies might also be appropriate in other parts of the world where directly observed treatment by health workers is not feasible. Our findings lend support to adoption of this patient-responsive approach to direct observation of treatment within global tuberculosis control policy.

Control of tuberculosis in an urban setting in Nepal: public-private partnership.

OBJECTIVES: To implement and evaluate a public-private partnership to deliver the internationally recommended strategy DOTS for the control of tuberculosis (TB) in Lalitpur municipality, Nepal, where it is estimated that 50% of patients with TB are managed in the private sector. METHODS: A local working group developed a public-private partnership for control of TB, which included diagnosis by private practitioners, direct observation of treatment and tracing of patients who missed appointments by nongovernmental organizations, and provision of training and drugs by the Nepal National TB Programme (NTP). The public-private partnership was evaluated through baseline and follow-up surveys of private practitioners, private pharmacies, and private laboratories, together with records kept by the Nepal NTP. FINDINGS: In the first 36 months, 1328 patients with TB were registered in the public-private partnership. Treatment success rates were >90%, and <1% of patients defaulted. Case notification of sputum-positive patients in the study area increased from 54 per 100 000 to 102 per 100 000. The numbers of patients with TB started on treatment by private practitioners decreased by more than two-thirds, the number of private pharmacies that stocked anti-TB drugs by one-third, the number of pharmacies selling anti-TB drugs by almost two-thirds, and sales of anti-TB drugs in pharmacies by almost two-thirds. Private practitioners were happy to refer patients to the public-private partnership. Not all private practitioners had to be involved: many patients bypassed private practitioners and went directly to free DOTS centres. CONCLUSIONS: A combination of the strengths of private practitioners, nongovernmental organizations, and the public sector in a public-private partnership can be used to provide a service that is liked by patients and gives high rates of treatment success and increased rates of patient notification. Similar public-private partnerships are likely to be replicable elsewhere, as inputs are not large and no special requirements exist.