Sputum Smear Microscopy at Two Months into Continuation-Phase: Should It Be Done in All Patients with Sputum Smear-Positive Tuberculosis?

BACKGROUND: The Revised National Tuberculosis Control Program (RNTCP) of India recommends follow-up sputum smear examination at two months into the continuation phase of treatment. The main intent of this (mid-CP) follow-up is to detect patients not responding to treatment around two-three months earlier than at the end of the treatment. However, the utility of mid-CP follow-up under programmatic conditions has been questioned. We undertook a multi-district study to determine if mid-CP follow-up is able to detect cases of treatment failures early among all types of patients with sputum smear-positive TB. METHODOLOGY: We reviewed existing records of patients with sputum smear-positive TB registered under the RNTCP in 43 districts across three states of India during a three month period in 2009. We estimated proportions of patients that could be detected as a case of treatment failure early, and assessed the impact of various policy options on laboratory workload and number needed to test to detect one case of treatment failure early. RESULTS: Of 10055 cases, mid-CP follow-up was done in 6944 (69%) cases. Mid-CP follow-up could benefit 117/8015 (1.5%) new and 206/2040 (10%) previously-treated sputum smear-positive cases by detecting their treatment failure early. Under the current policy, 31 patients had to be tested to detect one case of treatment failure early. All cases of treatment failure would still be detected early if mid-CP follow-up were discontinued for new sputum smear-positive cases who become sputum smear-negative after the intensive-phase of treatment. This would reduce the related laboratory workload by 69% and only 10 patients would need to be tested to detect one case of treatment failure early. CONCLUSION: Discontinuation of mid-CP follow-up among new sputum smear-positive cases who become sputum smear-negative after completing the intensive-phase of treatment will reduce the laboratory workload without impacting overall early detection of cases of treatment failure

Will adoption of the 2010 WHO ART guidelines for HIV-infected TB patients increase the demand for ART services in India?

BACKGROUND: In 2010, WHO expanded previously-recommended indications for anti-retroviral treatment to include all HIV-infected TB patients irrespective of CD4 count. India, however, still limits ART to those TB patients with CD4 counts <350/mm(3) or with extrapulmonary TB manifestations. We sought to evaluate the additional number of patients that would be initiated on ART if India adopted the current 2010 WHO ART guidelines for HIV-infected TB patients. METHODS: We evaluated all TB patients recorded in treatment registers of the Revised National TB Control Programme in June 2010 in the high-HIV prevalence state of Karnataka, and cross-matched HIV-infected TB patients with ART programme records. RESULTS: Of 6182 TB patients registered, HIV status was ascertained for 5761(93%) and 710(12%) were HIV-infected. 146(21%) HIV-infected TB patients were on ART prior to TB diagnosis. Of the remaining 564, 497(88%) were assessed for ART eligibility; of these, 436(88%) were eligible for ART according to 2006 WHO ART guidelines. Altogether, 487(69%) HIV-infected TB patients received ART during TB treatment. About 80% started ART within 8 weeks of TB treatment and 95% received an efavirenz based regimen. CONCLUSION: In Karnataka, India, about nine out of ten HIV-infected TB patients were eligible for ART according to 2006 WHO ART guidelines. The efficiency of HIV case finding, ART evaluation, and ART initiation was relatively high, with 78% of eligible HIV-infected patients actually initiated on ART, and 80% within 8 weeks of diagnosis. ART could be extended to all HIV-infected TB patients irrespective of CD4 count with relatively little additional burden on the national ART programme

Flow of cases of sputum smear-positive Tuberculosis as per successive sputum smear microscopy results.

<p>Mid-CP follow-up refers to the sputum smear microscopy which is scheduled between the 4^th and 6^th month of anti-TB treatment, i.e. in the middle of the ‘continuation phase’ (CP) of typical anti-TB treatment. Cases that are found to be smear-positive at 5^th month or later are considered as not responding to treatment (‘treatment failure’). Numerals shown in rectangular boxes refer to number of cases with treatment failure who were detected two-three months earlier than at the end of treatment as they were smear-positive in mid-CP follow-up at or beyond 5^th month of anti-TB treatment. Numerals shown in clear ovals refer to number of cases with treatment failure that were detected only at the end of treatment because they were either smear-negative in mid CP follow-up, or had a smear-positive mid-CP result before 5^th month of anti-TB treatment. Numerals shown in shaded ovals refer to number of cases with treatment failure who missed their mid-CP follow-up scheduled at or beyond 5^th month of treatment. These cases could have been detected two-three months earlier had they undergone mid-CP follow-up and were found to be smear-positive.</p

Timing of follow-up sputum smear examinations.

<p>Treatment duration and timing of follow-up sputum smear examinations for new and previously-treated cases of tuberculosis, highlighting the timing of the follow-up mid-continuation phase sputum smear examination. The initial two-three month intensive phase (light blue bars) is followed by a follow-up sputum smear examination (pink bars). If the follow-up sputum smear examination is positive, an additional 1-month extended-intensive phase treatment is given (dark blue bar), with additional follow-up sputum smear examination. After the intensive phase (or extended intensive phase), the continuation phase of treatment (grey bars) is immediately begin. After two months of continuation phase (i.e. between months 4 and 6), the mid-continuation phase (mid-CP) follow-up sputum smear examination is done (red bars, circled with dotted line). At the end of the continuation phase, a final follow-up sputum smear examination is done.</p

Impact of various policy options with regard to mid-CP follow-up on the number of cases of tuberculosis treatment failures detected early¹ and laboratory workload.

1<p>Detected as a case of treatment failure around two-three months earlier than if detected at the end of the treatment.</p>2<p>Percentage calculated by taking follow-up required under present policy as denominator.</p>3<p>Gain/Loss in absolute numbers indicated respectively by a positive or a negative sign; CP-Continuation Phase of TB treatment.</p

Timing of ART initiation and ART regimen in HIV-infected TB patients registered in Karnataka state, India, in June 2010.

<p>TB-Tuberculosis; HIV-Human immunodeficiency virus; ART-antiretroviral treatment.</p

Characteristics of HIV-infected TB patients registered in Karnataka state, India, in June 2010.

<p>*Percentages may not always add up to 100 due to rounding errors.</p><p>**There were 10 patients who had both pulmonary and extrapulmonary TB; they have been classified under extrapulmonary TB as they belong to HIV stage 4 and are ART eligible.</p><p>TB-Tuberculosis; HIV-Human immunodeficiency virus; CNS-Central Nervous System.</p

Eligibility for and initiation of antiretroviral treatment in HIV-infected TB patients registered in Karnataka state, India, in June 2010.

<p>*4 PTB patients were started on ART even though not eligible as per guidelines TB-Tuberculosis; HIV-Human immunodeficiency virus; PTB-pulmonary tuberculosis; EPTB-extrapulmonary tuberculosis; NACO-National AIDS Control Organization; ART-antiretroviral treatment; ARTC-ART centre.</p