Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise.

The current active-latent paradigm of tuberculosis largely neglects the documented spectrum of disease. Inconsistency with regard to definitions, terminology, and diagnostic criteria for different tuberculosis states has limited the progress in research and product development that are needed to achieve tuberculosis elimination. We aimed to develop a new framework of classification for tuberculosis that accommodates key disease states but is sufficiently simple to support pragmatic research and implementation. Through an international Delphi exercise that involved 71 participants representing a wide range of disciplines, sectors, income settings, and geographies, consensus was reached on a set of conceptual states, related terminology, and research gaps. The International Consensus for Early TB (ICE-TB) framework distinguishes disease from infection by the presence of macroscopic pathology and defines two subclinical and two clinical tuberculosis states on the basis of reported symptoms or signs of tuberculosis, further differentiated by likely infectiousness. The presence of viable Mycobacterium tuberculosis and an associated host response are prerequisites for all states of infection and disease. Our framework provides a clear direction for tuberculosis research, which will, in time, improve tuberculosis clinical care and elimination policies.

A SARS-CoV-2 coronavirus nucleocapsid protein antigen-detecting lateral flow assay.

Inexpensive, simple, rapid diagnostics are necessary for efficient detection, treatment, and mitigation of COVID-19. Assays for SARS-CoV2 using reverse transcription polymerase chain reaction (RT-PCR) offer good sensitivity and excellent specificity, but are expensive, slowed by transport to centralized testing laboratories, and often unavailable. Antigen-based assays are inexpensive and can be rapidly mass-produced and deployed at point-of-care, with lateral flow assays (LFAs) being the most common format. While various manufacturers have produced commercially available SARS-Cov2 antigen LFAs, access to validated tests remains difficult or cost prohibitive in low-and middle-income countries. Herein, we present a visually read open-access LFA (OA-LFA) using commercially-available antibodies and materials for the detection of SARS-CoV-2. The LFA yielded a Limit of Detection (LOD) of 4 TCID50/swab of gamma irradiated SARS-CoV-2 virus, meeting the acceptable analytical sensitivity outlined by in World Health Organization target product profile. The open-source architecture presented in this manuscript provides a template for manufacturers around the globe to rapidly design a SARS-CoV2 antigen test.

Antibody Screening Results for Anti-Nucleocapsid Antibodies Toward the Development of a Lateral Flow Assay to Detect SARS-CoV-2 Nucleocapsid Protein.

The global COVID-19 pandemic has created an urgent demand for large numbers of inexpensive, accurate, rapid, point-of-care diagnostic tests. Analyte-based assays are suitably rapid and inexpensive and can be rapidly mass-produced, but for sufficiently accurate performance, they require highly optimized antibodies and assay conditions. We used an automated liquid handling system, customized to handle arrays of lateral flow (immuno)assays (LFAs) in a high-throughput screen, to identify anti-nucleocapsid antibodies that will perform optimally in an LFA. We tested 1021 anti-nucleocapsid antibody pairs as LFA capture and detection reagents with the goal of highlighting pairs that have the greatest affinity for the nucleocapsid protein of SARS-CoV-2 within the LFA format. In contrast to traditional antibody screening methods (e.g., ELISA, bio-layer interferometry), the method described here integrates real-time reaction kinetics with transport in, and immobilization directly onto, nitrocellulose. We have identified several candidate antibody pairs that are suitable for further development of an LFA for SARS-CoV-2.

Screening Antibodies Raised against the Spike Glycoprotein of SARS-CoV-2 to Support the Development of Rapid Antigen Assays.

Severe acute respiratory coronavirus-2 (SARS-CoV-2) is a novel viral pathogen and therefore a challenge to accurately diagnose infection. Asymptomatic cases are common and so it is difficult to accurately identify infected cases to support surveillance and case detection. Diagnostic test developers are working to meet the global demand for accurate and rapid diagnostic tests to support disease management. However, the focus of many of these has been on molecular diagnostic tests, and more recently serologic tests, for use in primarily high-income countries. Low- and middle-income countries typically have very limited access to molecular diagnostic testing due to fewer resources. Serologic testing is an inappropriate surrogate as the early stages of infection are not detected and misdiagnosis will promote continued transmission. Detection of infection via direct antigen testing may allow for earlier diagnosis provided such a method is sensitive. Leading SARS-CoV-2 biomarkers include spike protein, nucleocapsid protein, envelope protein, and membrane protein. This research focuses on antibodies to SARS-CoV-2 spike protein due to the number of monoclonal antibodies that have been developed for therapeutic research but also have potential diagnostic value. In this study, we assessed the performance of antibodies to the spike glycoprotein, acquired from both commercial and private groups in multiplexed liquid immunoassays, with concurrent testing via a half-strip lateral flow assays (LFA) to indicate antibodies with potential in LFA development. These processes allow for the selection of pairs of high-affinity antispike antibodies that are suitable for liquid immunoassays and LFA, some of which with sensitivity into the low picogram range with the liquid immunoassay formats with no cross-reactivity to other coronavirus S antigens. Discrepancies in optimal ranking were observed with the top pairs used in the liquid and LFA formats. These findings can support the development of SARS-CoV-2 LFAs and diagnostic tools.

Tuberculosis preventive treatment: the next chapter of tuberculosis elimination in India.

The End TB Strategy envisions a world free of tuberculosis-zero deaths, disease and suffering due to tuberculosis by 2035. This requires reducing the global tuberculosis incidence from >1250 cases per million people to <100 cases per million people within the next two decades. Expanding testing and treatment of tuberculosis infection is critical to achieving this goal. In high-burden countries, like India, the implementation of tuberculosis preventive treatment (TPT) remains a low priority. In this analysis article, we explore potential challenges and solutions of implementing TPT in India. The next chapter in tuberculosis elimination in India will require cost-effective and sustainable interventions aimed at tuberculosis infection. This will require constant innovation, locally driven solutions to address the diverse and dynamic tuberculosis epidemiology and persistent programme monitoring and evaluation. As new tools, regimens and approaches emerge, midcourse adjustments to policy and practice must be adopted. The development and implementation of new tools and strategies will call for close collaboration between local, national and international partners-both public and private-national health authorities, non-governmental organisations, research community and the diagnostic and pharmaceutical industry. Leading by example, India can contribute to global knowledge through operational research and programmatic implementation for combating tuberculosis infection.

Unacceptable treatment outcomes and associated factors among India's initial cohorts of multidrug-resistant tuberculosis (MDR-TB) patients under the revised national TB control programme (2007-2011): Evidence leading to policy enhancement.

BACKGROUND: Globally, India has the world's highest burden of multidrug-resistant tuberculosis (MDR-TB). Programmatic Management of Drug Resistant TB (PMDT) in India began in 2007 and nationwide coverage was achieved in early 2013. Poor initial microbiological outcomes under the Revised National Tuberculosis Control Programme (RNTCP) prompted detailed analysis. This is the first study on factors significantly associated with poor outcomes in MDR-TB patients treated under the RNTCP. OBJECTIVE: To evaluate initial sputum culture conversion, culture reversion and final treatment outcomes among MDR-TB patients registered in India from 2007 to early 2011 who were treated with a standard 24-month regimen under daily-observed treatment. METHODS: This is a retrospective cohort study. Clinical and microbiological data were abstracted from PMDT records. Initial sputum culture conversion, culture reversion and treatment outcomes were defined by country adaptation of the standard WHO definitions (2008). Cox proportional hazards modeling with logistic regression, multinomial logistic regression and adjusted odds ratio was used to evaluate factors associated with interim and final outcomes respectively, controlling for demographic and clinical characteristics. RESULTS: In the cohort of 3712 MDR-TB patients, 2735 (73.6%) had initial sputum culture conversion at 100 median days (IQR 92-125), of which 506 (18.5%) had culture reversion at 279 median days (IQR 202-381). Treatment outcomes were available for 2264 (60.9%) patients while 1448 (39.0%) patients were still on treatment or yet to have a definite outcome at the time of analysis. Of 2264 patients, 781 (34.5%) had treatment success, 644 (28.4%) died, 670 (29.6%) were lost to follow up, 169 (7.5%) experienced treatment failure or were changed to XDR-TB treatment. Factors significantly associated with either culture non-conversion, culture reversion and/or unfavorable treatment outcomes were baseline BMI < 18; ≥ seven missed doses in intensive phase (IP) and continuation phase (CP); cavitary disease; prior treatment episodes characterized by re-treatment regimen taken twice, longer duration and more episodes of treatment; any weight loss during treatment; males and additional resistance to first line drugs (Ethambutol, Streptomycin). In a subgroup of 104 MDR-TB patients, 62 (59.6%) had Ofloxacin resistance among whom only 25.8% had treatment success, half of the success (54.8%) seen in Ofloxacin sensitive patients. Baseline susceptibility to Ofloxacin (HR 2.04) and Kanamycin (HR 4.55) significantly doubled and quadrupled the chances for culture conversion respectively while baseline susceptibility to Ofloxacin (AOR 0.37) also significantly reduced the odds of unfavorable treatment outcomes (p value ≤0.05) in multinomial logistic regression model. CONCLUSION: India's initial MDR-TB patients' cohort treated under the RNTCP experienced poor treatment outcomes. To address the factors associated with poor treatment outcomes revealed in our study, a systematic multi-pronged approach would be needed. A series of policies and interventions have been developed to address these factors to improve DR-TB treatment outcomes and are being scaled-up in India.

Evaluation of TB Case Finding through Systematic Contact Investigation, Chhattisgarh, India.

Rationale. Contact investigation is an established tool for early case detection of tuberculosis (TB). In India, contact investigation is not often conducted, despite national policy, and the yield of contact investigation is not well described. Objective. To determine the yield of evaluating household contacts of sputum smear-positive TB cases in Rajnandgaon district, Chhattisgarh, India. Methods. Among 14 public health care facilities with sputum smear microscopy services, home visits were conducted to identify household contacts of all registered sputum smear-positive TB cases. We used a standardized protocol to screen for clinical symptoms suggestive of active TB with additional referral for chest radiograph and sputa collection. Results. From December 2010 to May 2011, 1,556 household contacts of 312 sputum smear-positive TB cases were identified, of which 148 (9.5%) were symptomatic. Among these, 109 (73.6%) were evaluated by sputum examination resulting in 11 cases (10.1%) of sputum smear-positive TB and 4 cases (3.6%) of smear-negative TB. Household visits contributed additional 63% TB cases compared to passive case detection alone. Conclusion. A standard procedure for conducting household contact investigation identified additional TB cases in the community and offered an opportunity to initiate isoniazid chemoprophylaxis among children.

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India.

BACKGROUND: Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. METHODS: This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. RESULTS: In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. CONCLUSION: Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefold.

Airborne infection control in India: Baseline assessment of health facilities.

BACKGROUND: Tuberculosis transmission in health care settings represents a major public health problem. In 2010, national airborne infection control (AIC) guidelines were adopted in India. These guidelines included specific policies for TB prevention and control in health care settings. However, the feasibility and effectiveness of these guidelines have not been assessed in routine practice. This study aimed to conduct baseline assessments of AIC policies and practices within a convenience sample of 35 health care settings across 3 states in India and to assess the level of implementation at each facility after one year. METHOD: A multi-agency, multidisciplinary panel of experts performed site visits using a standardized risk assessment tool to document current practices and review resource capacity. At the conclusion of each assessment, facility-specific recommendations were provided to improve AIC performance to align with national guidelines. RESULT: Upon initial assessment, AIC systems were found to be poorly developed and implemented. Administrative controls were not commonly practiced and many departments needed renovation to achieve minimum environmental standards. One year after the baseline assessments, there were substantial improvements in both policy and practice. CONCLUSION: A package of capacity building and systems development that followed national guidelines substantially improved implementation of AIC policies and practice.

A multi-site validation in India of the line probe assay for the rapid diagnosis of multi-drug resistant tuberculosis directly from sputum specimens.

UNLABELLED: Rifampicin (R) and isoniazid (H) are key first-line anti-tuberculosis drugs. Failure to detect resistance to these two drugs early results in treatment failure and poor clinical outcomes. The study purpose was to validate the use of the GenoType MTBDRplus line probe assay (LPA) to detect resistance to R and H in Mycobacterium tuberculosis strains directly from smear-positive sputum samples in India. METHOD: Smear positive sputum specimens from 320 patients were subjected to LPA and results compared against those from conventional Lowenstein Jensen (LJ) culture and drug susceptibility testing (C&DST). All specimens with discordant R DST results were subjected to either sequencing of the rpoB gene and/or repeat DST on liquid culture (MGIT 960) at a National Reference Laboratory. RESULTS: Significantly higher proportion of interpretable results were observed with LPA compared to LJ C&DST (94% vs. 80%, p-value <0.01). A total of 248 patients had both LJ and LPA DST results available; 232 (93.5%) had concordant R DST results. Among the 16 discordant R DST results, 13 (81%) were resolved in agreement with LPA results. Final LPA performance characteristics were sensitivity 96% (CI: 90%-98%), specificity 99% (CI: 95%-99%), positive predictive value 99% (CI: 95%-99%), and negative predictive value 95% (CI: 89%-98%). The median turnaround testing time, including specimen transportation time, on LPA was 11 days as compared with 89 days for LJ C&DST. CONCLUSIONS: LPA proved highly accurate in the rapid detection of R resistance. The reduction in time to diagnosis may potentially enable earlier commencement of the appropriate drug therapy, leading to some reduction of transmission of drug-resistant strains.

Tuberculosis management practices by private practitioners in Andhra Pradesh, India.

SETTING: Private medical practitioners in Visakhapatnam district, Andhra Pradesh, India. OBJECTIVES: To evaluate self-reported TB diagnostic and treatment practices amongst private medical practitioners against benchmark practices articulated in the International Standards of Tuberculosis Care (ISTC), and factors associated with compliance with ISTC. DESIGN: Cross- sectional survey using semi-structured interviews. RESULTS: Of 296 randomly selected private practitioners, 201 (68%) were assessed for compliance to ISTC diagnostic and treatment standards in TB management. Only 11 (6%) followed a combination of 6 diagnostic standards together and only 1 followed a combination of all seven treatment standards together. There were 28 (14%) private practitioners who complied with a combination of three core ISTC (cough for tuberculosis suspects, sputum smear examination and use of standardized treatment). Higher ISTC compliance was associated with caring for more than 20 TB patients annually, prior sensitization to TB control guidelines, and practice of alternate systems of medicine. CONCLUSION: Few private practitioners in Visakhapatnam, India reported TB diagnostic and treatment practices that met ISTC. Better engagement of the private sector is urgently required to improve TB management practices and to prevent diagnostic delay and drug resistance.

Is one sputum specimen as good as two during follow-up cultures for monitoring multi drug resistant tuberculosis patients in India?

BACKGROUND: In India, the Revised National Tuberculosis Control Programme (RNTCP) has adopted the strategy of examining two specimens during follow-up culture examinations to monitor the treatment response of multi-drug resistant tuberculosis (MDR-TB) patients. OBJECTIVES: To determine the incremental yield of the second sputum specimen during follow-up culture examinations among patients with MDR-TB and the effect on case management on changing from two to one specimen follow-up strategy. METHODS: A cross sectional record review of MDR-TB patients registered during 2008-09 under RNTCP was undertaken in three MDR-TB treatment sites of India. RESULTS: Of 1721 pairs of follow-up sputum culture examinations done among 220 MDR-TB patients, 451(26%) were positive with either of the two specimens; 29(1.7%) were culture positive only on the second specimen indicating the incremental yield. To detect one additional culture positive result on the second specimen, 59 specimens needed to be processed. If we had examined only one specimen, we would have missed 29 culture-positive results. By current RNTCP guidelines, however, a single specimen policy would have altered case management in only 3(0.2%) instances, where patients would have missed a one month extension of the intensive phase of MDR-TB treatment. There is no meaningful advantage in using two specimens for the monitoring of MDR-TB patients. A single specimen policy could be safely implemented with negligible clinical effect on MDR-TB patients and favourable resource implications for RNTCP.

High diabetes prevalence among tuberculosis cases in Kerala, India.

BACKGROUND: While diabetes mellitus (DM) is a known risk factor for tuberculosis, the prevalence among TB patients in India is unknown. Routine screening of TB patients for DM may be an opportunity for its early diagnosis and improved management and might improve TB treatment outcomes. We conducted a cross-sectional survey of TB patients registered from June-July 2011 in the state of Kerala, India, to determine the prevalence of DM. METHODOLOGY/PRINCIPAL FINDINGS: A state-wide representative sample of TB patients in Kerala was interviewed and screened for DM using glycosylated hemoglobin (HbA1c); patients self-reporting a history of DM or those with HbA1c ≥6.5% were defined as diabetic. Among 552 TB patients screened, 243(44%) had DM - 128(23%) had previously known DM and 115(21%) were newly diagnosed - with higher prevalence among males and those aged >50 years. The number needed to screen(NNS) to find one newly diagnosed case of DM was just four. Of 128 TB patients with previously known DM, 107(84%) had HbA1c ≥7% indicating poor glycemic control. CONCLUSIONS/SIGNIFICANCE: Nearly half of TB patients in Kerala have DM, and approximately half of these patients were newly-diagnosed during this survey. Routine screening of TB patients for DM using HbA1c yielded a large number of DM cases and offered earlier management opportunities which may improve TB and DM outcomes. However, the most cost-effective ways of DM screening need to be established by futher operational research.

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.

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

SETTING: Under India's 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.

Perceptions of tuberculosis patients on provider-initiated HIV testing and counseling--a study from south India.

BACKGROUND: The acceptability and feasibility of provider-initiated HIV testing and counseling (PITC) in many settings across Asia with concentrated HIV epidemics is not known. A pilot study of the PITC policy undertaken within the public health care systems in two districts in India offered the opportunity to understand patient's perspectives on the process of referral for HIV testing and linking to HIV treatment and care. METHODS: We conducted a cross-sectional study of randomly selected TB patients registered by the TB control program between July and November 2007 in two districts in south India. Trained interviewers met patients shortly after TB diagnosis and administered a structured questionnaire. Patients were assessed regarding their experience with HIV status assessment, referral for counseling and testing, and for HIV-infected patients the counseling itself and subsequent referral for HIV treatment and care. RESULTS: Of the 568 interviewed TB patients, 455 (80%) reported being referred for HIV testing after they presented to the health facility for investigations or treatment for TB. Over half the respondents reported having to travel long distances and incurred financial difficulties in reaching the Integrated Counselling and Testing Centre (ICTC) and two-thirds had to make more than two visits. Only 48% reported having been counseled before the test. Of the 110 HIV-infected patients interviewed, (including 43 with previously-known positive HIV status and 67 detected by PITC), 89 (81%) reported being referred for anti-retroviral treatment (ART); 82 patients reached the ART centre but only 44 had been initiated on ART. CONCLUSIONS: This study provides the first evidence from India that routine, provider-initiated voluntary HIV testing of TB patients is acceptable, feasible and can be achieved with very high efficiency under programmatic conditions. While PITC is useful in identifying new HIV-infected patients so that they can be successfully linked to ART, the convenience and proximity of testing centres, quality of HIV counseling, and efficiency of ART services need attention.

Feasibility of provider-initiated HIV testing and counselling of tuberculosis patients under the TB control programme in two districts of South India.

BACKGROUND: Provider-initiated HIV testing and counselling (PITC) is internationally recommended for tuberculosis (TB) patients, but the feasibility, effectiveness, and impact of this policy on the TB programme in India are unknown. We evaluated PITC of TB patients across two districts in India considered to have generalized HIV epidemics, Tiruchirappalli (population 2.5 million) and Mysore (population 2.8 million). METHODOLOGY/PRINCIPAL FINDINGS: Starting June 2007, healthcare providers in both districts were instructed to ascertain HIV status for all TB patients, and refer those with unknown HIV status to the nearest Integrated Counselling and Testing Centre (ICTC)--often in the same facility--for counselling and voluntary HIV testing. All TB patients registered from June 2007 to March 2008 were followed prospectively. Field investigators assessed PITC practices and abstracted data from routine TB programme records and HIV counselling registers to determine the proportion of TB patients appropriately evaluated for HIV infection. Patient records were traced to determine the efficiency of referral links to HIV care and antiretroviral treatment (ART). Between July 2007 and March 2008, 5299 TB patients were registered in both study districts. Of the 4701 with unknown HIV status at the time of TB treatment initiation, 3368 (72%) were referred to an ICTC, and 3111 (66%) were newly tested for HIV. PITC implementation resulted in the ascertainment of HIV status for 3709/5299 (70%) of TB patients, and detected 200 cases with previously undiagnosed HIV infection. Overall, 468 (8.8%) of all registered TB patients were HIV-infected; 177 (37%) were documented to have also received any ART. CONCLUSIONS: With implementation of PITC in India, HIV status was successfully ascertained for 70% of TB patients. Previously undiagnosed HIV-infection was detected in 6.4% of those TB patients newly tested, enabling referral for life-saving anti-retroviral treatment. ART uptake, however, was poor, suggesting that PITC implementation should include measures to strengthen and support ART referral, evaluation, and initiation.

Linking HIV-infected TB patients to cotrimoxazole prophylaxis and antiretroviral treatment in India.

BACKGROUND: HIV-infected persons suffering from tuberculosis experience high mortality. No programmatic studies from India have documented the delivery of mortality-reducing interventions, such as cotrimoxazole prophylactic treatment (CPT) and antiretroviral treatment (ART). To guide TB-HIV policy in India we studied the effectiveness of delivering CPT and ART to HIV-infected persons treated for tuberculosis in three districts in Andhra Pradesh, India, and evaluated factors associated with death. METHODS AND FINDINGS: We retrospectively abstracted data for all HIV-infected tuberculosis patients diagnosed from March 2007 through August 2007 using standard treatment outcome definitions. 734 HIV-infected tuberculosis patients were identified; 493 (67%) were males and 569 (80%) were between the ages of 24-44 years. 710 (97%) initiated CPT, and 351 (50%) collected >60% of their monthly cotrimoxazole pouches provided throughout TB treatment. Access to ART was documented in 380 (51%) patients. Overall 130 (17%) patients died during TB treatment. Patients receiving ART were less likely to die (adjusted hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.3-0.6), while males and those with pulmonary TB were more likely to die (HR 1.7, 95% CI 1.1-2.7, and HR 1.9, 95% CI 1.1-3.2 respectively). CONCLUSIONS: Among HIV-infected TB patients in India death was common despite the availability of free cotrimoxazole locally and ART from referral centres. Death was strongly associated with the absence of ART during TB treatment. To minimize death, programmes should promote high levels of ART uptake and closely monitor progress in implementation.

Public-private mix TB activities in Meerut, Uttar Pradesh, North India: delivering dots via collaboration with private providers and non-governmental organizations.

BACKGROUND: We evaluated the contribution of public-private collaboration between the Indian tuberculosis (TB) programme and the private health sector (including non-governmental organizations and private providers) to TB case-detection and treatment outcomes in Meerut district, India. METHODOLOGY: District TB registers from January 2001-June 2003 were reviewed. RESULTS: The 2002 new AFB-positive case-notification rate (103/100,000 population) in Meerut exceeded national targets. Of the 7,062 new AFB-positive patients registered, 2,084 (29%) were detected at private sector microscopy and DOTS treatment centres; treatment outcomes met programme targets. CONCLUSION: Public-private collaborations can be successfully implemented at the district level in India, and have the potential for substantial contributions to TB control efforts in India.