Why are people dying due to tuberculosis? A study from Alappuzha District, Kerala, India.

BACKGROUND: Tuberculosis (TB)is a major killer disease worldwide. It is the ninth leading cause of death worldwide and the leading cause from a single infectious agent. In India also, TB kills about 480,000 persons every year and more than 1400 every day. Vision of the National TB Control Programme is TB-Free India with zero deaths, disease and poverty due to TB. Specific targets set in the End TB strategy include a 90% reduction in TB deaths and an 80% reduction in TB incidence by 2030, compared with 2015. Understanding about real cause of death is important to plan strategies to further prevent TB deaths. In the above circumstances we conducted a study, the objective of which was to find out the cause of deaths among patients registered in RNTCP unit of Alappuzha district of Kerala, India. METHODS: In RNTCP a patient who died during the course of treatment regardless of cause is declared as 'Died' due to TB. During the year 2015, 1618 cases were registered in RNTCP of Alappuzha district of which 90 patients died, showing a case fatality rate of 5.56%. Verbal autopsy can be considered as an essential public health tool for studying reasonable estimate of the cause of death at a community level even though not an accurate method at individual level. As part of the study, we visited the 4 RNTCP units of the district and collected the address of the TB patients who died in the area. With the help of the field staff we visited their houses and filled the death audit form of RNTCP along with the additional details. Verbal autopsy was conducted using WHO verbal autopsy format 2012 with immediate house hold contacts. RESULTS: Out of 90 deaths which occurred, three addresses could not be traced and another 15 patient relatives could not be contacted as they migrated out or were not available at their homes on two visits. Among them, mean age was found to be 62.6 years (SD+12.9). Males were 67 (77%) and rest 20 (23%)were females. Cause of death was analysed after Verbal autopsy for 72 deaths. Among 72 deaths, it was found that 29 (40.3%) had nothing other than TB, where as cause of death for 13 (18.1%) patients was myocardial infarction, 11 (15.3%) had cancer, 2 (2.8%) stroke and 17 (23.7%) other causes which include bronchiectasis, COPD, chicken pox, hepatitis, renal failure, and suicide. Only in 35 cases nothing other than TB could be suggested as a cause of death. Thus in 52 out of 87 (60%) cases, the causes of death were diseases other than TB. CONCLUSION: Among the TB deaths in Alappuzha district, 60% of deaths were due to diseases other than TB. Along with early diagnosis of all TB cases, screening for co-morbidity, appropriate management of co-morbidity and periodic clinical review of TB patients should also be part of the major strategies to prevent TB related deaths.

Utility of the microcolony method for evaluation of multidrug-resistant tuberculosis patients in Karachi, Pakistan.

OBJECTIVE: To compare the microcolony method (MCM) with the reference culture method to evaluate culture conversion in multidrug-resistant tuberculosis (MDR-TB) patients.MATERIAL AND METHODS: Adult patients with Mycobacterium tuberculosis culture-positive MDR-TB undergoing second-line anti-tuberculosis treatment were recruited from two tertiary care chest clinics from January 2013 to October 2014. The MCM was performed in addition to MGIT™ and Löwenstein-Jensen medium (reference method) on sputum samples submitted on a monthly basis.RESULTS: Of 140 patients, culture conversion could be evaluated in 95 patients. The MCM showed 100% agreement with the reference M. tuberculosis culture in 83 of 95 patients who achieved culture conversion. In smear-positive and smear-negative cases, the mean time to positivity was 9.1 and 11.4 days for the MCM and 16.1 and 23.2 days for the reference M. tuberculosis culture respectively. The contamination rate for the MCM was 4.5% in comparison with 6.1% for the reference M. tuberculosis culture. The cost of MCM was estimated to be 30% that of the reference method.CONCLUSION: The MCM can be used in non-urban laboratories as a safe, rapid and cost-effective substitute for the reference M. tuberculosis culture to assess culture conversion in MDR-TB patients.Note: Abstract has been published in International Journal of Mycobacteriology 2015; 4: 159-160.

[Budget impact of the incorporation of GeneXpert MTB/RIF for diagnosis of pulmonary tuberculosis from the perspective of the Brazilian Unified National Health System, Brazil, 2013-2017]. / Impacto orçamentário da incorporação do GeneXpert MTB/RIF para o diagnóstico da tuberculose pulmonar na perspectiva do Sistema Único de Saúde, Brasil, 2013-2017.

The study aimed to estimate the budget impact of GeneXpert MTB/RIF for diagnosis of tuberculosis from the perspective of the Brazilian National Program for Tuberculosis Control, drawing on a static model using the epidemiological method, from 2013 to 2017. GeneXpert MTB/RIF was compared with two diagnostic sputum smear tests. The study used epidemiological, population, and cost data, exchange rates, and databases from the Brazilian Unified National Health System. Sensitivity analysis of scenarios was performed. Incorporation of GeneXpert MTB/RIF would cost BRL 147 million (roughly USD 45 million) in five years and would have an impact of 23 to 26% in the first two years and some 11% between 2015 and 2017. The results can support Brazilian and other Latin American health administrators in planning and managing the decision on incorporating the technology.

Resumo: O objetivo do estudo foi estimar o impacto orçamentário do GeneXpert MTB/RIF para o diagnóstico da tuberculose sob a perspectiva do Programa Nacional de Controle da Tuberculose, valendo-se de um modelo estático apoiado no método epidemiológico entre 2013 e 2017. Comparou-se um teste Xpert MTB/RIF com duas baciloscopias diagnósticas. Utilizaram-se dados epidemiológicos, populacionais, de custos, a taxa de câmbio e bases de dados do Sistema Único de Saúde. Foi realizada análise de sensibilidade por cenários. A incorporação do GeneXpert MTB/RIF demandaria um montante de R$ 147 milhões em cinco anos e representaria um impacto de 23% a 26% nos dois primeiros anos, e de cerca de 11% entre 2015 e 2017. Os resultados podem apoiar os gestores brasileiros e dos países latino-americanos no planejamento e gestão na sua decisão de incorporação da tecnologia.

Resumen: El objetivo del estudio fue estimar el impacto presupuestario del GeneXpert MTB/RIF para el diagnóstico de la tuberculosis, desde la perspectiva del Programa Nacional de Control de la Tuberculosis de Brasil, valiéndose de un modelo estático, apoyado en el método epidemiológico entre 2013 y 2017. Se comparó un test Xpert MTB/RIF con dos baciloscopias diagnósticas. Se utilizaron datos epidemiológicos, poblacionales, de costes, la tasa de cambio y bases de datos del Sistema Único de Salud. Se realizó un análisis de sensibilidad por escenarios. La incorporación del GeneXpert MTB/RIF demandaría un montante de R$ 147 millones en cinco años y representaría un impacto de 23 a 26% durante los dos primeros años, y de cerca de un 11% entre 2015 y 2017. Los resultados pueden apoyar a los gestores brasileiros y de los países latinoamericanos en la planificación y gestión a la hora de decidir incorporar este tipo de tecnología.

Impacto orçamentário da incorporação do GeneXpert MTB/RIF para o diagnóstico da tuberculose pulmonar na perspectiva do Sistema Único de Saúde, Brasil, 2013-2017 / Budget impact of the incorporation of GeneXpert MTB/RIF for diagnosis of pulmonary tuberculosis from the perspective of the Brazilian Unified National Health System, Brazil, 2013-2017 / Impacto presupuestario de la incorporación del GeneXpert MTB/RIF para el diagnóstico de la tuberculosis pulmonar desde la perspectiva del Sistema Único de Salud, Brasil, 2013-2017

Resumo: O objetivo do estudo foi estimar o impacto orçamentário do GeneXpert MTB/RIF para o diagnóstico da tuberculose sob a perspectiva do Programa Nacional de Controle da Tuberculose, valendo-se de um modelo estático apoiado no método epidemiológico entre 2013 e 2017. Comparou-se um teste Xpert MTB/RIF com duas baciloscopias diagnósticas. Utilizaram-se dados epidemiológicos, populacionais, de custos, a taxa de câmbio e bases de dados do Sistema Único de Saúde. Foi realizada análise de sensibilidade por cenários. A incorporação do GeneXpert MTB/RIF demandaria um montante de R$ 147 milhões em cinco anos e representaria um impacto de 23% a 26% nos dois primeiros anos, e de cerca de 11% entre 2015 e 2017. Os resultados podem apoiar os gestores brasileiros e dos países latino-americanos no planejamento e gestão na sua decisão de incorporação da tecnologia.

Abstract: The study aimed to estimate the budget impact of GeneXpert MTB/RIF for diagnosis of tuberculosis from the perspective of the Brazilian National Program for Tuberculosis Control, drawing on a static model using the epidemiological method, from 2013 to 2017. GeneXpert MTB/RIF was compared with two diagnostic sputum smear tests. The study used epidemiological, population, and cost data, exchange rates, and databases from the Brazilian Unified National Health System. Sensitivity analysis of scenarios was performed. Incorporation of GeneXpert MTB/RIF would cost BRL 147 million (roughly USD 45 million) in five years and would have an impact of 23 to 26% in the first two years and some 11% between 2015 and 2017. The results can support Brazilian and other Latin American health administrators in planning and managing the decision on incorporating the technology.

Resumen: El objetivo del estudio fue estimar el impacto presupuestario del GeneXpert MTB/RIF para el diagnóstico de la tuberculosis, desde la perspectiva del Programa Nacional de Control de la Tuberculosis de Brasil, valiéndose de un modelo estático, apoyado en el método epidemiológico entre 2013 y 2017. Se comparó un test Xpert MTB/RIF con dos baciloscopias diagnósticas. Se utilizaron datos epidemiológicos, poblacionales, de costes, la tasa de cambio y bases de datos del Sistema Único de Salud. Se realizó un análisis de sensibilidad por escenarios. La incorporación del GeneXpert MTB/RIF demandaría un montante de R$ 147 millones en cinco años y representaría un impacto de 23 a 26% durante los dos primeros años, y de cerca de un 11% entre 2015 y 2017. Los resultados pueden apoyar a los gestores brasileiros y de los países latinoamericanos en la planificación y gestión a la hora de decidir incorporar este tipo de tecnología.

The economic burden of TB diagnosis and treatment in South Africa.

Social protection against the cost of illness is a central policy objective of Universal Health Coverage and the post-2015 Global strategy for Tuberculosis (TB). Understanding the economic burden associated with TB illness and care is key to identifying appropriate interventions towards achieving this target. The aims of this study were to identify points in patient pathways from start of TB symptoms to treatment completion where interventions could be targeted to reduce the economic impact on patients and households, and to identify those most vulnerable to these costs. Two cohorts of patients accessing TB services from ten clinics in four provinces in South Africa were surveyed between July 2012 and June 2013. One cohort of 351 people with suspected TB were interviewed at the point of receiving a TB diagnostic and followed up six months later. Another cohort of 168 patients on TB treatment, at the same ten facilities, was interviewed at two-months and five-months on treatment. Patients were asked about their health-seeking behaviour, associated costs, income loss, and coping strategies used. Patients incurred the greatest share of TB episode costs (41%) prior to starting treatment, with the largest portion of these costs being due to income loss. Poorer patients incurred higher direct costs during treatment than those who were less poor but only 5% of those interviewed were accessing cash-transfers during treatment. Indirect costs accounted for 52% of total episode cost. Despite free TB diagnosis and care in South Africa, patients incur substantial direct and indirect costs particularly prior to starting treatment. The poorest group of patients were incurring higher costs, with fewer resources to pay for it. Both the direct and indirect cost of illness should be taken into account when setting levels of financial protection and social support, to prevent TB illness from pushing the poor further into poverty.

Factors contributing to the high prevalence of multidrug-resistant tuberculosis among previously treated patients: a case-control study from China.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) has emerged as a serious global public health problem. In China, the risk factors for MDR-TB have not been systematically evaluated. OBJECTIVE: To identify risk factors associated with MDR-TB among previously treated patients in China. DESIGN: A case-control study was carried out. Cases were selected from previously treated MDR-TB patients who were resistant to both isoniazid and rifampin, and controls were selected from previously treated TB patients who were sensitive to isoniazid and rifampin (non-MDR-TB). Information was collected from the registration database and a structured questionnaire. RESULTS: A total of 61 cases and 50 controls were recruited. A multivariate analysis showed that the family annual per-capita income ≤7,000 Yuan (odds ratio [OR]=3.238; 95% confidence interval [CI]: 1.270-8.252), no history of fixed dose combinations (FDCs) in anti-TB treatment (OR=4.027; 95% CI: 1.457-11.129), and adverse reactions in the course of TB treatment (OR=3.568; 95% CI: 1.402-9.085) were independent predictors of MDR-TB. Moreover, among the TB patients who had adverse reactions, quitting the treatment was shown as a risk factor for MDR-TB (p=0.009). CONCLUSION: In the control of MDR-TB among previously treated patients, lower socioeconomic groups, the expanding use of FDCs, and improving adherence to treatment by implementing Directly Observed Therapy Short Course-Plus (DOTS-Plus), strictly should become a priority that requires strong commitment and collaboration among health organizations.

Determinants of consultation, diagnosis and treatment delays among new smear-positive pulmonary tuberculosis patients in Morocco: a cross-sectional study.

We conducted a cross-sectional survey in 2012 in 12 selected provinces and prefectures in Morocco to determine consultation delay (patient delay), diagnosis delay and treatment delay (health system delays), and factors relating to these delays. The sample included 250 eligible and consenting newly diagnosed smearpositive pulmonary tuberculosis patients who were interviewed at the time of their registration within Diagnosis of Tuberculosis and Respiratory Diseases Reference Centers (CDTMR) or Integrated Health Centers (CSI) using a pretested and structured questionnaire. The median total delay was 46 days [inter-quartile interval (IQI) = 29-84 days]. Patient delay (median = 20; IQI = 8-47 days) was higher than health system delay (median=15; IIQ = 7-35 days). Being illiterate, thinking symptoms will disappear by themselves; having financial constraints and feeling fear of diagnosis or social isolation were associated with patient delay. Consulting first in the private sector or having 3 or more consultations before diagnosis was associated with health system delay.

Household contact investigation for tuberculosis in Vietnam: study protocol for a cluster randomized controlled trial.

BACKGROUND: Tuberculosis is an infectious disease that continues to cause considerable morbidity and mortality globally. Only 65% of patients worldwide are currently diagnosed. Contact investigation is a strategy that aims to increase case detection and reduce transmission of tuberculosis, yet there is little evidence to show its effectiveness. METHODS/DESIGN: We will conduct a cluster randomized controlled trial of contact investigation within the national tuberculosis control program of Vietnam. Household contacts of patients with smear-positive pulmonary tuberculosis will be invited to attend district tuberculosis units for symptom screening, examination, and chest radiography on four occasions over a two-year period. The primary endpoint is clinically confirmed tuberculosis among contacts during the 24 months of follow-up, ascertained using capture-recapture analysis. Microbiologically proven tuberculosis and treatment completion rates among contacts diagnosed with tuberculosis will be secondary endpoints. The incremental cost-effectiveness ratio will be estimated. The study will have 80% power to detect a 50% increase in the primary endpoint in the active intervention arm compared with the control arm. The study will include 8,829 contacts in each of the active screening and control groups, within 70 districts in 8 provinces in Vietnam, in both rural and urban settings. DISCUSSION: The effectiveness of contact investigation as a tool for improved tuberculosis case finding has not been established. This cluster randomized trial will provide valuable operational information for national tuberculosis programs in high-prevalence countries, in order to select the most cost-effective strategies to improve tuberculosis case detection. TRIAL REGISTRATION: The ACT2 study has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000600044).

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%).

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.

[Diffculties in medico-social management of tuberculosis in Pneumology Departement of Fann University Teaching Hospital]. / Difficultés dans la prise en charge médico-sociale de la tuberculose a la clinique de Pneumologie du CHU de Fann.

This prospective study included all the patients who, during the month of September 1995, were admitted for pulmonary baclliferous tuberculosis to the Pneumology Clinic of the Fann University Hospital, Dakar. The patient's escorts and the health personnel were also included in this study. The aim of the study was to find the different socio-economic and health factors impeding the hospitalization of tuberculosis patients in the Pneumology Clinic of Fann University Hospital. 22 members of the health team, 209 patients aged between 15 and 65 years and 209 escorts were interviewed. Out of the 10% of tuberculosis patients with HIV seropositivity, 80% admitted not to have informed their spouses of their infection. The decision to be admitted was made by the patient himself in 54.4% of cases and by his family in 45.5% of cases. Late admittance with regards to the beginning of symptoms was due to the recourse to traditional medicine in 43.7% of cases, wrong diagnosis in 24%, ignorance in 19.3% and, in 13% of cases, due to inappropiate anti tuberculosis treatment. Despite the fact that anti tuberculosis medicine was free of charge, each patient or his family spent an average sum of 87,500 CFA F (US dollar 175) for a month's admission (the minimal salary (SMIG) in Senegal is 32,000 CFA F (US dollar 64), and 40% of the patients and escorts had difficulties making this payment. 9 patients were judged to be poor by 25.7% of the patients and 8.7% found relations with the health personnel difficult. The escorts deplored the lack of toilets (only 1 out of 4 was functional), the time worn facilities, the overcrowding as well as the irregularity and poor quality of the hospital meals. The entire health team deplored the lack of adequate personnel and 30% of them deplored the lack of hygiene of some patients and escorts. Taking financial charge of tuberculosis patients at the Pneumology Clinic of the Fann University Hospital requires an increased financial effort from the State (rehabilitation of the facilities, recruitment of medical and paramedical personnel, improved meals) harmonisation on a national scale of anti tuberculosis therapeutic protocoles and an Information-Education-Communication (IEC) programme on tuberculosis and hygiene.

Cost-effectiveness of community health workers in tuberculosis control in Bangladesh.

OBJECTIVE: To compare the cost-effectiveness of the tuberculosis (TB) programme run by the Bangladesh Rural Advancement Committee (BRAC), which uses community health workers (CHWs), with that of the government TB programme which does not use CHWs. METHODS: TB control statistics and cost data for July 1996 - June 1997 were collected from both government and BRAC thanas (subdistricts) in rural Bangladesh. To measure the cost per patient cured, total costs were divided by the total number of patients cured. FINDINGS: In the BRAC and government areas, respectively, a total of 186 and 185 TB patients were identified over one year, with cure rates among sputum-positive patients of 84% and 82%. However, the cost per patient cured was US$ 64 in the BRAC area compared to US$ 96 in the government area. CONCLUSION: The government programme was 50% more expensive for similar outcomes. Although both the BRAC and government TB control programmes appeared to achieve satisfactory cure rates using DOTS (a five-point strategy), the involvement of CHWs was found to be more cost-effective in rural Bangladesh. With the same budget, the BRAC programme could cure three TB patients for every two in the government programme.

Treatment costs of directly observed therapy and traditional therapy for Mycobacterium tuberculosis: a comparative analysis.

OBJECTIVE: Treatment of tuberculosis is a time-consuming and expensive process, often complicated by patient non-adherence. Directly observed therapy (DOT), an out-patient management strategy designed to ensure adherence, is not widely used because it is perceived to be too expensive. This study compared costs of tuberculosis treatment in DOT to the same factors in traditional therapy. DESIGN: A retrospective economic evaluation of 659 tuberculosis cases was reported to a major metropolitan county public health department between 1980 and 1994. Out-patient costs, in-patient costs and the cost impact of relapse and acquired resistance were estimated in 1995 dollars. RESULTS: Treatment costs were lower with DOT: $15,670 per case for in-patient care and $700 per case for out-patient care (P < 0.001). These cost differences resulted from shorter therapy duration (334 vs 550 days), fewer patient hospitalizations (58 vs 75%) and shorter hospital stays (26 vs 55 days per hospitalized patient). Relapse or acquired resistance occurred in 10.9% of patients and accounted for 35.7% of cost with traditional therapy, as compared to 1.2% of patients and 6.0% of cost with observed therapy. CONCLUSIONS: Directly observed therapy is less costly than traditional therapy.