Devesh Gupta

Updated national guidelines for pediatric tuberculosis in India, 2012.

In response to letter from Sahu, we wish to inform that: (a) the group extensively deliberated about appropriate doses for anti-TB drugs to be recommended for our country based on available evidence and concluded that the earlier recommended dosages needed revision. The current dosages were arrived after looking into various available pharmacokinetic data and evidence within and outside the country (published and unpublished data from studies at AIIMS and NIRT). The group arrived at these recommendations as a consensus, while keeping in mind the absolute need for adequate serum levels and also the possible risk of cumulative hepatotoxicity; (b) the group recommends the total duration of ATT in intracranial TB including TB Meningitis should be 9-12 months depending upon the clinical progress on treatment. This is in consonance with available evidence and experience; and (c) among retreatment cases, the INH resistance is significant but not absolute, hence a third drug ethambutol, is added to in the continuation phase (RHE). There is no scientific basis or evidence for including pyrazinamide instead of ethambutol in the continuation phase. Pyrazinamide works best when there is active inflammation and in acidic pH, hence its benefit may not be seen during the continuation phase [1]. Furthermore, addition of Ethambutol not only helps in preventing emergence of drug resistance [2] but also would minimize the potential risk of hepato-toxicity with prolonged use of the suggested three hepatotoxic drugs (RHZ).

Risk factors for treatment default among re-treatment tuberculosis patients in India, 2006.

Setting Under Indias Revised National Tuberculosis Control Programme (RNTCP), >15% of previously-treated patients in the reported 2006 patient cohort defaulted from anti-tuberculosis treatment. Objective To assess the timing, characteristics, and risk factors for default amongst re-treatment TB patients. Methodology For this case-control study, in 90 randomly-selected programme units treatment records were abstracted from all 2006 defaulters from the RNTCP re-treatment regimen (cases), with one consecutively-selected non-defaulter per case. Patients who interrupted anti-tuberculosis treatment for >2 months were classified as defaulters. Results 1,141 defaulters and 1,189 non-defaulters were included. The median duration of treatment prior to default was 81 days (25%–75% interquartile range 44–117 days) and documented retrieval efforts after treatment interruption were inadequate. Defaulters were more likely to have been male (adjusted odds ratio [aOR] 1.4, 95% confidence interval [CI] 1.2–1.7), have previously defaulted anti-tuberculosis treatment (aOR 1.3 95%CI 1.1–1.6], have previous treatment from non-RNTCP providers (AOR 1.3, 95%CI 1.0–1.6], or have public health facility-based treatment observation (aOR 1.3, 95%CI 1.1–1.6). Conclusions Amongst the large number of re-treatment patients in India, default occurs early and often. Improved pre-treatment counseling and community-based treatment provision may reduce default rates. Efforts to retrieve treatment interrupters prior to default require strengthening.

The profile and treatment outcomes of the older (aged 60 years and above) tuberculosis patients in Tamilnadu, South India.

Background With changing demographic patterns in the context of a high tuberculosis (TB) burden country, like India, there is very little information on the clinical and demographic factors associated with poor treatment outcome in the sub-group of older TB patients. The study aimed to assess the proportion of older TB patients (60 years of age and more), to compare the type of TB and treatment outcomes between older TB patients and other TB patients (less than 60 years of age) and to describe the demographic and clinical characteristics of older TB patients and assess any associations with TB treatment outcomes. Methods A retrospective cohort study involving a review of records from April to June 2011 in the 12 selected districts of Tamilnadu, India. Demographic, clinical and WHO defined disease classifications and treatment outcomes of all TB patients aged 60 years and above were extracted from TB registers maintained routinely by Revised National TB Control Program (RNTCP). Results Older TB patients accounted for 14% of all TB patients, of whom 47% were new sputum positive. They had 38% higher risk of unfavourable treatment outcomes as compared to all other TB patients (Relative risk (RR)-1.4, 95% CI 1.2–1.6). Among older TB patients, the risk for unfavourable treatment outcomes was higher for those aged 70 years and more (RR 1.5, 95% CI 1.2–1.9), males (RR 1.5, 95% CI 1.0–2.1), re-treatment patients (RR 2.5, 95% CI 1.9–3.2) and those who received community-based Direct Observed Treatment (RR 1.4, 95% CI 1.1–1.9). Conclusion Treatment outcomes were poor in older TB patients warranting special attention to this group – including routine assessment and recording of co-morbidities, a dedicated recording, reporting and monitoring of outcomes for this age-group and collaboration with National programme of non-communicable diseases for comprehensive management of co-morbidities.

Feasibility and effectiveness of provider initiated HIV testing and counseling of TB suspects in Vizianagaram district, South India.

Background Though internationally recommended, provider initiated HIV testing and counseling (PITC) of persons suspected of tuberculosis (TB) is not a policy in India; HIV seroprevalence among TB suspects has never been reported. The current policy of PITC for diagnosed TB cases may limit opportunities of early HIV diagnosis and treatment. We determined HIV seroprevalence among persons suspected of TB and assessed feasibility and effectiveness of PITC implementation at this earlier stage in the TB diagnostic pathway. Methods All adults examined for diagnostic sputum microscopy (TB suspects) in Vizianagaram district (population 2.5 million), in November-December 2010, were offered voluntary HIV counseling and testing (VCT) and assessed for TB diagnosis. Results Of 2918 eligible TB suspects, 2465(85%) consented to VCT. Among these, 246(10%) were HIV-positive. Of the 246, 84(34%) were newly diagnosed as HIV (HIV status not known previously). To detect a new case of HIV infection, the number needed to screen (NNS) was 26 among ‘TB suspects’, comparable to that among ‘TB patients’. Among suspects aged 25–54 years, not diagnosed as TB, the NNS was 17. Conclusion The seroprevalence of HIV among ‘TB suspects’ was as high as that among ‘TB patients’. Implementation of PITC among TB suspects was feasible and effective, detecting a large number of new HIV cases with minimal additional workload on staff of HIV testing centre. HIV testing of TB suspects aged 25–54 years demonstrated higher yield for a given effort, and should be considered by policy makers at least in settings with high HIV prevalence.

What are the reasons for poor uptake of HIV testing among patients with TB in an Eastern India District

Background National policy in India recommends HIV testing of all patients with TB. In West Bengal state, only 28% of patients with TB were tested for HIV between April-June, 2010. We conducted a cross-sectional survey to understand patient, provider and health system related factors associated with low uptake of HIV testing among patients with TB. Methods We reviewed TB and HIV program records to assess the HIV testing status of patients registered for anti-TB treatment from July-September 2010 in South-24-Parganas district, West Bengal, assessed availability of HIV testing kits and interviewed a random sample of patients with TB and providers. Results Among 1633 patients with TB with unknown HIV status at the time of diagnosis, 435 (26%) were tested for HIV within the intensive phase of TB treatment. Patients diagnosed with and treated for TB at facilities with co-located HIV testing services were more likely to get tested for HIV than at facilities without [RR = 1.27, (95% CI 1.20–3.35)]. Among 169 patients interviewed, 67 reported they were referred for HIV testing, among whom 47 were tested. During interviews, providers attributed the low proportion of patients with TB being referred and tested for HIV to inadequate knowledge among providers about the national policy, belief that patients will not test for HIV even if they are referred, shortage of HIV testing kits, and inadequate supervision by both programs. Discussion In West Bengal, poor uptake of HIV testing among patients with TB was associated with absence of HIV testing services at sites providing TB care services and to poor referral practices among providers. Comprehensive strategies to change providers’ beliefs and practices, decentralization of HIV testing to all TB care centers, and improved HIV test kit supply chain management may increase the proportion of patients with TB who are tested for HIV.

HIV Testing among Patients with Presumptive Tuberculosis: How Do We Implement in a Routine Programmatic Setting? Results of a Large Operational Research from India.

Background In March 2012, World Health Organization recommended that HIV testing should be offered to all patients with presumptive TB (previously called TB suspects). How this is best implemented and monitored in routine health care settings in India was not known. An operational research was conducted in Karnataka State (South India, population 64 million, accounts for 10% of India’s HIV burden), to test processes and learn results and challenges of screening presumptive TB patients for HIV within routine health care settings. Methods In this cross-sectional study conducted between January-March 2012, all presumptive TB patients attending public sector sputum microscopy centres state-wide were offered HIV testing by the laboratory technician, and referred to the nearest public sector HIV counselling and testing services, usually within the same facility. The HIV status of the patients was recorded in the routine TB laboratory form and TB laboratory register. The laboratory register was compiled to obtain the number of presumptive TB patients whose HIV status was ascertained, and the number found HIV positive. Aggregate data on reasons for non-testing were compiled at district level. Results Overall, 115,308 patients with presumptive TB were examined for sputum smear microscopy at 645 microscopy centres state-wide. Of these, HIV status was ascertained for 62,847(55%) among whom 7,559(12%) were HIV-positive, and of these, 3,034(40%) were newly diagnosed. Reasons for non-testing were reported for 37,700(72%) of the 52,461 patients without HIV testing; non-availability of testing services at site of sputum collection was cited by health staff in 54% of respondents. Only 4% of patients opted out of HIV testing. Conclusion Offering HIV testing routinely to presumptive TB patients detected large numbers of previously-undetected instances of HIV infection. Several operational challenges were noted which provide useful lessons for improving uptake of HIV testing in this important group.

HIV testing in people with presumptive tuberculosis: time for implementation

Despite progress in the global response to the dual epidemic of HIV/AIDS and tuberculosis, an estimated 1·8 million people died from AIDS-related diseases in 2010, including 350 000 deaths from HIV-associated tuberculosis. In view of the fact that HIV/AIDS is treatable, albeit with lifelong therapy, and drug-sensitive tuberculosis is curable, such high mortality rates are unacceptable. WHO and the Joint UN Programme on HIV/AIDS (UNAIDS) have both embraced a bold vision of “zero new HIV infections, zero discrimination and zero AIDS-related deaths” by 2015, which has been reinforced by the 2012 World Tuberculosis Day theme that emphasises “zero tuberculosis deaths”. In March, 2012, WHO launched its updated policy on collaborative tuberculosis and HIV activities, with some important new recommendations, one of which was that routine HIV testing and counselling should be off ered not only to patients diagnosed with tuberculosis, but also to all those being investigated for possible tuberculosis (hereafter referred to as presumptive tuberculosis). This recommendation implies that the HIV testing intervention should be moved upstream in the tuberculosis diagnostic pathway. In this Comment, we emphasise the logic behind this recommendation, argue that it will help to reduce mortality from HIV/AIDS and HIV-associated tuberculosis, and suggest how it can be implemented and monitored. The results of several studies in sub-Saharan Africa and India have shown that the prevalence of HIV in individuals with presumptive tuberculosis is as high as that in patients with diagnosed tuberculosis, with prevalence varying according to the epidemiological context. Some data show that people with presumptive tuberculosis who are sputum smear negative and infected with HIV generally fare poorly. For example, 63% of patients with presumptive tuberculosis in Zimbabwe were infected with HIV; 85% had CD4 cell counts lower than 350 cells per μL; and during a 12-month follow up, 25% were diagnosed and treated for tuberculosis, 16% died, and only 15% started antiretroviral therapy. These poor outcomes could be substantially improved by some simple interventions. First, if patients with HIV infection and presumptive tuberculosis are provided with structured HIV care that involves CD4 cell count assessment, co-trimoxazole preventive therapy, and antiretroviral therapy, this package will protect against serious HIV-related opportunistic infections, reverse immune defi ciency, and prevent tuberculosis. Second, such patients can be prioritised for new, high-sensitivity rapid diagnostics for tuberculosis, such as the nucleic acid amplifi cation test, Xpert MTB/ RIF (Cepheid, Sunnyvale, CA, USA). This test confi rms tuberculosis disease within 2 h, and provides additional information about rifampicin resistance, which helps to improve the treatment and management strategy. Third, if a diagnosis of active tuberculosis can be confi dently excluded, isoniazid preventive therapy can be used, for which there is increasing evidence for an additive and synergistic benefi t when combined with antiretroviral therapy. Although to move HIV testing upstream in settings of high HIV prevalence makes intuitive sense, further evidence is needed for whether such a policy actually reduces morbidity and mortality in settings of low HIV prevalence, in view of the resource implications. Although HIV testing and counselling in patients with diagnosed tuberculosis is widely implemented, monitored, and reported, testing for HIV in patients

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/mm3 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.

Strategy and way forward for TB elimination

Indias National Strategic Plan (NSP) for TB Elimination 2017-25 looks ambitious in terms of targets of TB notification aiming to reach 35 lakh TB patients annually, i.e. double that of current status. Strategies and interventions designed under the Plan with patient centered approaches, with synergistic public-private-patient partnership can make it possible to achieve real aim of reaching the unreached, by extending patient support systems and social protection to affected communities. In this review point, these strategies and commitments are summarized as future plan.