Pharmacy based surveillance for identifying missing tuberculosis cases: A mixed methods study from South India.

BACKGROUND: No Indian studies have assessed the implementation of recent policy on pharmacy based surveillance and its contribution in TB notification. So, this study was conducted with objectives to describe: a) pharmacy based TB surveillance and TB notification, and b) experiences of pharmacy based surveillance implementation from the programme managers and pharmacists perspective. METHODS: A mixed methods study-quantitative (cross-sectional) and qualitative (in-depth interviews) in two selected districts Dharmapuri and Salem districts of Tamil Nadu State, India. RESULTS: In 2018, 45 (11%) of 397 pharmacies in Dharmapuri and 90 (6%) of 1457 pharmacies in Salem districts reported sale of anti-TB drugs to 1307 and 1673 persons respectively. Upon validation through direct patient contact 942 (72%) persons in Dharmapuri and 863 (52%) persons were identified as previously 'un-notified' TB patients. These patients constituted 20% and 29% of the total TB cases notified in Dharmapuri and Salem respectively. The enablers for implementing this activity were: understanding the importance of notification, availability of resources (manpower, computers) to record, report and validate the patient data, repeated trainings and partnerships. The barriers were: patients' hesitancy to share their details to pharmacists (confidentiality), cumbersome recording and reporting process, difficulties in recording patient details during high workload busy business hours. CONCLUSION: This process contributed about one-fourth of the TB patients notified in these districts. Its implementation needs to be strengthened and should be scaled up in other parts of the country.

Extensively Drug-resistant Tuberculosis (XDR-TB): A daunting challenge to the current End TB Strategy and policy recommendations.

Extensively Drug-resistant Tuberculosis (XDR-TB) has emerged as one of the most formidable challenges to the End TB Strategy that has targeted a 95% reduction in TB deaths and 90% reduction in cases by 2035. Globally, there were an estimated 55,100 new XDR-TB cases in 2015 in 117 countries. However, only one in 30 XDR-TB cases had been reported so far. Drug susceptibility test (DST) is the mainstay for diagnosing XDR-TB, but the lack of laboratory facilities in the resource-limited endemic countries limit its uses. A few new drugs including bedaquiline and delamanid, have the potential to improve the efficiency of XDR-TB treatment, but the drugs have been included in 39 countries only. The costs of XDR-TB treatment are several folds higher than that of the MDR-TB. Despite the financing from the donors, there is an urgent need to fill the current funding gap of US$ 2 billion to ensure effective treatment and robust surveillance. In the review article we have addressed current update on XDR-TB, including surveillance, diagnosis and the interventions needed to treat and limit its spread, emphasis on extensive financial support for implementing of current recommendations to meet the goals of End TB Strategy.

Second line drug susceptibility testing to inform the treatment of rifampin-resistant tuberculosis: a quantitative perspective.

Treatment failure and resistance amplification are common among patients with rifampin-resistant tuberculosis (TB). Drug susceptibility testing (DST) for second-line drugs is recommended for these patients, but logistical difficulties have impeded widespread implementation of second-line DST in many settings. To provide a quantitative perspective on the decision to scale up second-line DST, we synthesize literature on the prevalence of second-line drug resistance, the expected clinical and epidemiologic benefits of using second-line DST to ensure that patients with rifampin-resistant TB receive effective regimens, and the costs of implementing (or not implementing) second-line DST for all individuals diagnosed with rifampin-resistant TB. We conclude that, in most settings, second-line DST could substantially improve treatment outcomes for patients with rifampin-resistant TB, reduce transmission of drug-resistant TB, prevent amplification of drug resistance, and be affordable or even cost-saving. Given the large investment made in each patient treated for rifampin-resistant TB, these payoffs would come at relatively small incremental cost. These anticipated benefits likely justify addressing the real challenges faced in implementing second-line DST in most high-burden settings.

Cost-effectiveness of a 12-dose regimen for treating latent tuberculous infection in the United States.

SETTING: A large randomized controlled trial recently showed that for treating latent tuberculous infection (LTBI) in persons at high risk of progression to tuberculosis (TB) disease, a 12-dose regimen of weekly rifapentine plus isoniazid (3HP) administered as directly observed treatment (DOT) can be as effective as 9 months of daily self-administered isoniazid (9H). OBJECTIVES: To assess the cost-effectiveness of 3HP compared to 9H. DESIGN: A computational model was designed to simulate individuals with LTBI treated with 9H or 3HP. Costs and health outcomes were estimated to determine the incremental costs per active TB case prevented and per quality-adjusted life year (QALY) gained by 3HP compared to 9H. RESULTS: Over a 20-year period, treatment of LTBI with 3HP rather than 9H resulted in 5.2 fewer cases of TB and 25 fewer lost QALYs per 1000 individuals treated. From the health system and societal perspectives, 3HP would cost respectively US$21,525 and $4294 more per TB case prevented, and respectively $4565 and $911 more per QALY gained. CONCLUSIONS: 3HP may be a cost-effective alternative to 9H, particularly if the cost of rifapentine decreases, the effectiveness of 3HP can be maintained without DOT, and 3HP treatment is limited to those with a high risk of progression to TB disease.

Analysis of the economic burden of diagnosis and treatment of tuberculosis patients in rural China.

SETTING: A county in Jiangsu Province, China. OBJECTIVES: To estimate the costs of the diagnosis and treatment of tuberculosis (TB) from the patient's perspective and to identify determinants of the patient's financial burden. DESIGN: In a cross-sectional survey, we interviewed 316 patients diagnosed from January 2010 to May 2011 who had already completed their anti-tuberculosis treatment. The financial burden on TB patients included out-of-pocket costs and productivity losses. RESULTS: The average per capita total out-of-pocket cost was 3024.0 Chinese yuan (CNY), with a median cost of 1086 CNY (interquartile range [IQR] 480-2456). Mean out-of-pocket medical and non-medical costs were respectively 2565.7 CNY and 458.3 CNY. Productivity lost by patients and family members was 2615.2 CNY (median 500, IQR 250-2025). Factors associated with out-of-pocket costs and productivity losses included hospitalisation, adverse drug reactions, cost of drugs to 'protect' the liver, cost of second-line anti-tuberculosis drugs and diagnostic delay. CONCLUSION: Although the government of China has implemented a 'free TB service policy', the economic burden on patients is still heavy. More patient-centred interventions are essential to reduce the financial burden on patients.

Associations between national tuberculosis program budgets and tuberculosis outcomes: an ecological study.

INTRODUCTION: The objective of this study is to explore the associations between national tuberculosis program (NTP) budget allocation and tuberculosis related outcomes in the World Health Organization's 22 high burden countries from 2007-2009. METHODS: This ecological study used mixed effects and generalized estimating equation models to identify independent associations between NTP budget allocations and various tuberculosis related outcomes. Models were adjusted for a number of independent variables previously noted to be associated with tuberculosis incidence. RESULTS: Increasing the percent of the NTP budget for advocacy, communication and social mobilization was associated with an increase in the case detection rate. Increasing TB-HIV funding was associated with an increase in HIV testing among TB patients. Increasing the percent of the population covered by the Directly Observed Therapy (DOT) program was associated with an increase in drug susceptibility testing. Laboratory funding was positively associated with tuberculosis notification. Increasing the budgets for first line drugs, management and multi-drug resistant tuberculosis (MDR-TB) was associated with a decrease in smear positive deaths. CONCLUSION: Effective TB control is a complex and multifaceted challenge. This study revealed a number of budget allocation related factors associated with improved TB outcome parameters. If confirmed with future longitudinal studies, these findings could help guide NTP managers with allocation decisions.

Costs associated with tuberculosis diagnosis and treatment in Yemen for patients and public health services.

This study determined the costs associated with tuberculosis (TB) diagnosis and treatment for the public health services and patients in Sana'a, Yemen. Data were collected prospectively from 320 pulmonary and extrapulmonary TB patients (160 each) who were followed until completion of treatment. Direct medical and nonmedical costs and indirect costs were calculated. The proportionate cost to the patients for pulmonary TB and extrapulmonary TB was 76.1% arid 89.4% respectively of the total for treatment. The mean cost to patients for pulmonary and extrapulmonary TB treatment was US$ 108.4 and US$ 328.0 respectively. The mean cost per patient to the health services for pulmonary and extrapulmonary TB treatment was US$ 34.0 and US$ 38.8 respectively. For pulmonary and extrapulmonary TB, drug treatment represented 59.3% and 77.9% respectively of the total cost to the health services. The greatest proportionate cost to patients for pulmonary TB treatment was time away from work (67.5% of the total cost), and for extrapulmonary TB was laboratory and X-ray costs (55.5%) followed by transportation (28.6%).

New drugs for the treatment of tuberculosis: needs, challenges, promise, and prospects for the future.

For the first time in 40 years, a portfolio of promising new compounds for the treatment of tuberculosis is on the horizon. The introduction of new drugs in combination treatment for all forms of tuberculosis raises several issues related to patients' access to novel treatments, programmatic feasibility, cost effectiveness, and implications for monitoring and surveillance, particularly with regard to the development of drug resistance. Particular attention should be given to the identification of optimal drug combination(s) for the treatment of all forms of tuberculosis, particularly in high-risk and vulnerable groups, such as human immunodeficiency virus-coinfected persons and children, and to the rational use of new drugs. Addressing these issues adequately requires the establishment of clear guidelines to assist countries in the development of policies for the proper use of tuberculosis drugs in a way that guarantees access to best treatments for all those in need and avoids inappropriate use of new drugs. After a description of these various challenges, we present activities that will be carried out by the World Health Organization in collaboration with key stakeholders for the development of policy guidelines for optimal treatment of tuberculosis.

Integrated delivery of HIV and tuberculosis services in sub-Saharan Africa: a systematic review.

Tuberculosis is a major cause of morbidity and mortality in people with HIV and about a quarter of HIV-related deaths are attributed to tuberculosis. In this Review we identify and synthesise published evidence for the effectiveness and cost-effectiveness of eight integrated strategies recommended by WHO that represent coordinated delivery of HIV and tuberculosis services. Evidence supports concurrent screening for tuberculosis and HIV, and provision of either co-trimoxazole during routine tuberculosis care or isoniazid during routine HIV care and at voluntary counselling and testing centres. Although integration of antiretroviral therapy into tuberculosis care has shown promise for improving health outcomes for patients, evidence is insufficient to make conclusive claims. Evidence is also insufficient on the accessibility of condoms at tuberculosis facilities, the benefits of risk reduction counselling in patients with tuberculosis, and the effectiveness of tuberculosis infection control in HIV health-care settings. The vertical response to the tuberculosis and HIV epidemics is ineffective and inefficient. Implications for policy makers and funders include further investments in implementing integrated tuberculosis and HIV programmes with known effectiveness, preferably in a way that strengthens health systems; evaluative research that identifies barriers to integration; and research on integrated strategies for which effectiveness, efficiency, and affordability are not well established.

Is there a role for patent medicine vendors in tuberculosis control in southern Nigeria?

Patent medicine vendors (PMVs) are a ubiquitous feature of the informal health sector in Nigeria. A previous study on healthcare-seeking behaviour of persons with chronic cough in southern Nigeria found that over 60% of respondents chose the PMV as a healthcare provider of first instance. This study sought to determine the willingness and capability of PMVs to play a role in the national tuberculosis (TB)-control effort. Study sites were selected through a multi-stage sampling process. In total, 388 PMVs, 17 principal officers of PMV associations, and 17 community leaders were purposively selected. Sets of structured questionnaire were administered to the PMVs while information from the principal officers of PMV associations and community leaders was elicited through in-depth interviews and focus-group discussions (FGDs). Quantitative data were collated using the Epi Info software (version 6.04) and analyzed using the SPSS software (version 15). Most (90%) PMVs indicated that they would be ready to cooperate with the national TB-control programme, if trained. Seventy-three percent attended persons with prolonged cough in the course of their career. However, 48% did not know the cause of TB. Only 3% ever-attended a training session on TB control. Sixty-six percent completed at least 12 years of schooling with secondary school certificate. Eighty percent of the community leaders were happy with the work of PMVs. About two-thirds (65.6%) of the PMVs were male. The PMVs are positively disposed to playing roles in TB control. Given this positive disposition and their widespread acceptance in healthcare-delivery in the communities, they have potentials for playing a role in TB control in southern Nigeria.

Economic evaluation of public-private mix for tuberculosis care and control, India. Part I. Socio-economic profile and costs among tuberculosis patients.

SETTING: Bangalore City, India. OBJECTIVES: To assess the socio-economic profile, health-seeking behaviour and costs related to tuberculosis (TB) diagnosis and treatment among patients treated under the Revised National TB Control Programme (RNTCP). DESIGN: All 1106 new TB patients registered for treatment under the RNTCP in the second quarter of 2005 participated. Interviews at the beginning and at the end of treatment were conducted. A convenience sample of 32 patients treated outside the RNTCP also participated. RESULTS: Among the TB patients, respectively 50% and 39% were from low and middle standard of living (SL) households, and 77% were from households with a per capita income of less than US$1 per day. The first health contact was with a private practitioner in the case of >70% of patients. Mean patient delay was low, at 21 days, but the mean health system delay was 52 days. The average cost incurred by patients before treatment in the RNTCP was US$145, and during treatment it was US$21. Costs as a proportion of annual household income per capita were 53% for people from low SL households and 41% for those from other households. Costs during treatment faced by patients treated outside the RNTCP averaged US$127. CONCLUSION: Patients treated under the RNTCP through a public-private mix approach were predominantly poor. Many of them experienced considerable health expenditures before starting treatment. Additional efforts are required to reduce the delays and the number of health care providers consulted, and to ensure that patients are shifted to subsidised treatment within the RNTCP.

Economic evaluation of public-private mix for tuberculosis care and control, India. Part II. Cost and cost-effectiveness.

SETTING: Bangalore City, India. OBJECTIVES: To assess the cost and cost-effectiveness of public-private mix (PPM) for tuberculosis (TB) care and control when implemented on a large scale. DESIGN: DOTS implementation under the Revised National TB Control Programme (RNTCP) began in 1999, PPM was introduced in mid-2001 and a second phase of intensified PPM began in 2003. Data on the costs and effects of TB treatment from 1999 to 2005 were collected and used to compare the two distinct phases of PPM with a scenario of no PPM. Costs were assessed in 2005 $US for public and private providers, patients and patient attendants. Sources of data included expenditure records, medical records, interviews with staff and patient surveys. Effectiveness was measured as the number of cases successfully treated. RESULTS: When PPM was implemented, total provider costs increased in proportion to the number of successfully treated TB cases. The average cost per patient treated from the provider perspective when PPM was implemented was stable, at US$69, in the intensified phase compared with US$71 pre-PPM. PPM resulted in the shift of an estimated 7200 patients from non-DOTS to DOTS treatment over 5 years. PPM implementation substantially reduced costs to patients, such that the average societal cost per patient successfully treated fell from US$154 to US$132 in the 4 years following the initiation of PPM. CONCLUSION: Implementation of PPM on a large scale in an urban setting can be cost-effective, and considerably reduces the financial burden of TB for patients.

Latent tuberculosis infection in children: a call for revised treatment guidelines.

BACKGROUND: Guidelines for latent tuberculosis infection do not consider drug-resistance patterns when recommending treatment for immigrant children. OBJECTIVES: The purpose of this research was to decide at what rate of isoniazid resistance a different regimen other than isoniazid for 9 months should be considered. METHODS: We constructed a decision tree by using published data. We studied 3 regimens considered to be effective for susceptible organisms: (1) isoniazid for 9 months, (2) rifampin for 6 months, and (3) isoniazid for 9 months plus rifampin for 6 months. In addition, we evaluated a regimen of isoniazid and rifampin for 3 months. Our base case was a 2-year-old child from Russia with a tuberculin skin test reaction of 12 mm. We assumed a societal perspective and expressed results as cost and cost per case of tuberculosis prevented. We conducted sensitivity analyses to test the stability of our model. RESULTS: In our baseline analysis, rifampin was the least costly treatment regimen for any child arriving from an area with an isoniazid-resistance rate of >/=11%. Treatment with isoniazid plus rifampin was the most effective but would cost more than $1 million per reactivation case prevented. Isoniazid would become the least costly regimen if any of the following thresholds were met: rifampin resistance given isoniazid resistance of more than 82%; rifampin resistance given no isoniazid resistance of >9%; cost of rifampin more than $47/month; effectiveness of rifampin lower than 63%; effectiveness of isoniazid higher than 74%; and cost of pulmonary tuberculosis less than $7661. Isoniazid and rifampin for 3 months was the least costly for all cases from areas with isoniazid resistance of <80% as long as the regimen's effectiveness was >50% for susceptible bacteria. However, this assumption remains to be proven. CONCLUSION: Because of the high prevalence of isoniazid resistance, rifampin should be considered for children with latent tuberculosis infection originating from countries with >11% isoniazid resistance.

In vitro drug resistance and response to therapy in pulmonary tuberculosis patients under a DOTS programme in south India.

Tuberculosis (TB) patients (n=605) whose pre-treatment sputum culture yielded Mycobacterium tuberculosis were studied for the association of in vitro resistance to anti-TB drugs and treatment outcome. Five hundred and fifty-four (92%) patients showed favourable outcome, while 51 (8%) showed unfavourable outcome to anti-TB treatment. Logistic regression analysis of the data revealed that male gender (Wald P=0.026) and multidrug resistance (MDR) (Wald P<0.001) were associated with unfavourable outcome. Proportion of treatment failure (6%) was higher in patients who had received earlier anti-TB drug therapy (re-treated patients) compared with the newly diagnosed patients (2%). Re-treated patients yielded more drug-resistant M. tuberculosis, including MDR (P<0.001), than new cases. Treatment guided by in vitro drug susceptibility tests may therefore be more effective and less expensive for such selected cases.

Cost of illness of tuberculosis in Penang, Malaysia.

OBJECTIVE: To assess the costs incurred by the public health services and patients as a result of tuberculosis (TB) treatment. Setting The study was conducted in a government hospital located in the northern region of Malaysia. METHOD: Retrospective data were collected from medical records and the patients were observed until the completion of their medication. A pharmacoeconomic evaluation was applied to calculate direct and indirect costs. MAIN OUTCOME MEASURE: Direct and indirect costs of tuberculosis treatment in a government health institution. RESULTS: Two hundred and one tuberculosis patients were included in the study. Different regimens with various durations of treatments were used. The direct medical and non-medical costs as well as indirect costs were calculated and were found to be as follows: US$61.44 for anti-tuberculosis drugs and supplies, US$28.63 for X-ray examinations, US$28.53 for laboratory tests, US$20.03 for healthcare staff time, US$4.28 for hospitalisation, US$43.20 for overhead costs, US$608.11 for transportation and meals and US$118.78 for time away from work. The cost to the patients constitutes approximately 80% of the total cost of the treatment. CONCLUSION: The cost of treating the illness of tuberculosis per patient was US$916.4. The cost of anti-tuberculosis drugs constituted the highest proportion of the cost to the public health services (31.7%) while the cost to the patient constituted the major proportion of the total cost of the illness (79.4%).

The Global Drug Facility: a unique, holistic and pioneering approach to drug procurement and management.

In January 2006, the Stop TB Partnership launched the Global Plan to Stop TB 2006-2015, which describes the actions and resources needed to reduce tuberculosis (TB) incidence, prevalence and deaths. A fundamental aim of the Global Plan is to expand equitable access to affordable high-quality anti-tuberculous drugs and diagnostics. A principal tool developed by the Stop TB Partnership to achieve this is the Global Drug Facility (GDF). This paper demonstrates the GDFs unique, holistic and pioneering approach to drug procurement and management by analysing its key achievements. One of these has been to provide 9 million patient-treatments to 78 countries in its first 6 years of operation. The GDF recognized that the incentives provided by free or affordable anti-tuberculosis drugs are not sufficient to induce governments to improve their programmes standards and coverage, nor does the provision of free or affordable drugs guarantee that there is broad access to, and use of, drug treatment in cases where procurement systems are weak, regulatory hurdles exist or there are unreliable distribution and storage systems. Thus, the paper also illustrates how the GDF has contributed towards making sustained improvements in the capacity of countries worldwide to properly manage their anti-TB drugs. This paper also assesses some of the limitations, shortcomings and risks associated with the model. The paper concludes by examining the GDFs key plans and strategies for the future, and the challenges associated with implementation.