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

The performance and yield of tuberculosis testing algorithms using microscopy, chest x-ray, and Xpert MTB/RIF

Setting: The introduction of Xpert MTB/RIF (Xpert) and renewed interest in chest x-ray (CXR) for tuberculosis testing has provided additional choices to the smear-based diagnostic algorithms used by TB programs previously. More programmatic data is needed to better understand the implications of possible approaches. Objective: We sought to evaluate how different testing algorithms using microscopy, Xpert and CXR impacted the number of people detected with TB in a district hospital in Nepal. Design: Consecutively recruited patients with TB-related symptoms were offered smear microscopy, CXR and Xpert. We tested six hypothetical algorithms and compared yield, bacteriologically positive (Bac+) cases missed, and tests conducted. Results: Among 929 patients, Bac+ prevalence was 17.3% (n = 161). Smear microscopy detected 121 (75.2% of Bac+). Depending on the radiologists’ interpretation of CXR, Xpert testing could be reduced by (31%–60%). Smear microscopy reduced Xpert cartridge need slightly, but increased the overall diagnostic tests performed. Conclusion: Xpert detected a large proportion of Bac+ TB cases missed by microscopy. CXR was useful in greatly reducing the number of diagnostic tests needed even among presumptive TB patients. Loose CXR readings should be used to identify more people for TB testing. More analysis of costs and standardized CXR reading should be considered. Keywords: Diagnostic algorithms Chest X-ray, Xpert MTB/RIF, Case detection, Tuberculosi

Characteristics of the study population.

<p>SD = Standard Deviation; IQR = Inter Quartile Range.</p

MDR-TB treatment centers and sub-centers in Nepal.

<p>Footnote <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008313#pone-0008313-g001" target="_blank">Figure 1:</a> In 2005–2006, not all the health centres were functioning. The 175 cases included in this study were under care at 17 clinics (Bhaktapur, Bheri, Bir, Genetup, Haraicha, HelpHand, INF_Banke, KohalpurMC, Mahakali, Mangalbare, NATA, NMC, NTC, Patan, RTC, Stupa, and TUTH).</p

Months till death (N = 14, thick line) or default (N = 29, dotted line) for MDR-TB cases, Nepal, 2005–2006.

<p>Months till death (N = 14, thick line) or default (N = 29, dotted line) for MDR-TB cases, Nepal, 2005–2006.</p

Resistance to first-line anti-TB drugs at baseline DST.

<p>Resistance to first-line anti-TB drugs at baseline DST.</p

Treatment outcomes for MDR-TB cases by region, Nepal, 2005–2006.

<p>Treatment outcomes for MDR-TB cases by region, Nepal, 2005–2006.</p

Variables associated with cure.

<p>Variables associated with cure.</p

Major adverse events registered in the study cohort.

<p>Major adverse events registered in the study cohort.</p