Bottom-up or top-down: unit cost estimation of tuberculosis diagnostic tests in India.

SETTING: Of 18 sites that participated in an implementation study of the Xpert® MTB/RIF assay in India, we selected five microscopy centres and two reference laboratories. OBJECTIVE: To obtain unit costs of diagnostic tests for tuberculosis (TB) and drug-resistant TB. DESIGN: Laboratories were purposely selected to capture regional variations and different laboratory types. Both bottom-up and the top-down methods were used to estimate unit costs. RESULTS: At the microscopy centres, mean bottom-up unit costs were respectively US$0.83 (range US$0.60-US$1.10) and US$12.29 (US$11.61-US$12.89) for sputum smear microscopy and Xpert. At the reference laboratories, mean unit costs were US$1.69 for the decontamination procedure, US$9.83 for a solid culture, US$11.06 for a liquid culture, US$29.88 for a drug susceptibility test, and US$18.18 for a line-probe assay. Top-down mean unit cost estimates were higher for all tests, and for sputum smear microscopy and Xpert these increased to respectively US$1.51 and US$13.58. The difference between bottom-up and top-down estimates was greatest for tests performed at the reference laboratories. CONCLUSION: These unit costs for TB diagnostics can be used to estimate resource requirements and cost-effectiveness in India, taking into account geographical location, laboratory type and capacity utilisation

Care seeking and attitudes towards treatment compliance by newly enrolled tuberculosis patients in the district treatment programme in rural western Kenya: a qualitative study

<p>Abstract</p> <p>Background</p> <p>The two issues mostly affecting the success of tuberculosis (TB) control programmes are delay in presentation and non-adherence to treatment. It is important to understand the factors that contribute to these issues, particularly in resource limited settings, where rates of tuberculosis are high. The objective of this study is to assess health-seeking behaviour and health care experiences among persons with pulmonary tuberculosis, and identify the reasons patients might not complete their treatment.</p> <p>Methods</p> <p>We performed qualitative one-on-one in-depth interviews with pulmonary tuberculosis patients in nine health facilities in rural western Kenya. Thirty-one patients, 18 women and 13 men, participated in the study. All reside in an area of western Kenya with a Health and Demographic Surveillance System (HDSS). They had attended treatment for up to 4 weeks on scheduled TB clinic days in September and October 2005.</p> <p>The nine sites all provide diagnostic and treatment services. Eight of the facilities were public (3 hospitals and 5 health centres) and one was a mission health centre.</p> <p>Results</p> <p>Most patients initially self-treated with herbal remedies or drugs purchased from kiosks or pharmacies before seeking professional care. The reported time from initial symptoms to TB diagnosis ranged from 3 weeks to 9 years. Misinterpretation of early symptoms and financial constraints were the most common reasons reported for the delay.</p> <p>We also explored potential reasons that patients might discontinue their treatment before completing it. Reasons included being unaware of the duration of TB treatment, stopping treatment once symptoms subsided, and lack of family support.</p> <p>Conclusions</p> <p>This qualitative study highlighted important challenges to TB control in rural western Kenya, and provided useful information that was further validated in a quantitative study in the same area.</p

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

Estimating the annual risk of infection with Mycobacterium tuberculosis among adolescents in Western Kenya in preparation for TB vaccine trials

Background: Adolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations. Methods: Adolescents aged 12-18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 h for reading. A TST of ≥10 mm if HIV negative or ≥ 5 mm if HIV positive, was considered positive. Results: Of 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1, 95% CI 29.2-35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2-3.1). Risk factors for a positive TST included being male (OR 1.3, 95% CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95% CI 1.2,1.8), having a BCG scar (OR 1.5,95% CI 1.2,1.8), living in a rural area (OR 1.4, 95% CI 1.1,1.9), and being out of school (OR 1.8, 95% CI 1.4,2.3). Conclusion: We conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Dramatic and sustained increase in HIV-testing rates among antenatal attendees in Eastern Uganda after a policy change from voluntary counselling and testing to routine counselling and testing for HIV: a retrospective analysis of hospital records, 2002-2009

<p>Abstract</p> <p>Background</p> <p>The burden of mother-to-child transmission of HIV in Uganda is high. The aim of this paper is to describe the experience of the first 7 years of the prevention of mother- to- child transmission of HIV (PMTCT) programme in Mbale Regional Hospital, Eastern Uganda, with particular reference to the lessons learnt in changing from voluntary counselling and testing (VCT) to routine counselling and testing (RCT) for HIV testing in antenatal services.</p> <p>Methods</p> <p>The study was a retrospective analysis of the PMTCT records of Mbale Regional Referral Hospital, Uganda, from May 2002 to April 2009. The data on HIV testing of pregnant women and their male partners was extracted from the reports and registers using a standardized data extraction form, and data was analysed using descriptive statistics. Permission to conduct the study was obtained from School of Medicine, Makerere University College of Health Sciences; Uganda National Council of Science and Technology, and Mbale Hospital.</p> <p>Results</p> <p>A total of 54 429 new antenatal (ANC) attendees and 469 male-partners accessed antenatal services at Mbale Regional Referral Hospital. There was a sustained, significant increase in HIV testing among new ANC attendees from 22% during the VCT period to 88% during the RCT period (<it>p </it>= 0.002), while among male partners, HIV testing increased from 88% to 100% (<it>p </it>= 0.010) However, the overall number of male partners who tested for HIV remained very low despite the change from VCT to RCT approach in HIV testing.</p> <p>Conclusions</p> <p>Routine offer of antenatal HIV testing dramatically increased HIV testing in pregnant women and their partners in Uganda. Our findings call for further strengthening of the policy for routine HIV testing in antenatal clinics. Our study also showed that male partner HIV testing in antenatal clinics is low and this area needs further work through research and innovative interventions in order to improve male partner involvement.</p

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone

Cost-effectiveness of rapid susceptibility testing against second-line drugs for tuberculosis

Drug susceptibility testing (DST) against second-line tuberculosis drugs (SLDs) is essential for improving outcomes among multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) cases. To evaluate the potential cost-effectiveness of rapid DST for SLDs. We constructed a decision analysis model of Xpert MTB/RIF-based TB diagnosis in East and South-East Asia to compare culture-based DST vs. a hypothetical rapid SLD DST system for specimens resistant to rifampin. Our primary outcomes were the effectiveness and incremental cost-effectiveness of a rapid SLD DST assay relative to culture-based DST. For rapid SLD DST to be more effective than culture-based DST, treating individuals with pre-XDR/XDR-TB with a standardized MDR-TB regimen while awaiting culture-based DST must incur at least 30% excess XDR-TB mortality (100% = treatment with first-line drugs); rapid SLD DST should attain an aggregate sensitivity and specificity for all pre-XDR/XDR mutations of 88% and 96%, respectively. The unit cost of the rapid SLD DST assay must approach that of culture to achieve common thresholds for cost-effectiveness in low-income countries. Rapid SLD DST has the potential to be cost-effective, but must meet stringent criteria for accuracy and costs, and requires that standardized second-line treatment for pre-XDR/XDR-TB incur substantial excess mortality before the return of culture result

Diagnostic practices and estimated burden of tuberculosis among children admitted to 13 government hospitals in Kenya: An analysis of two years’ routine clinical data

BACKGROUND:True burden of tuberculosis (TB) in children is unknown. Hospitalised children are low-hanging fruit for TB case detection as they are within the system. We aimed to explore the process of recognition and investigation for childhood TB using a guideline-linked cascade of care. METHODS:This was an observational study of 42,107 children admitted to 13 county hospitals in Kenya from 01Nov 15-31Oct 16, and 01Nov 17-31Oct 18. We estimated those that met each step of the cascade, those with an apparent (or "Working") TB diagnosis and modelled associations with TB tests amongst guideline-eligible children. RESULTS:23,741/42,107 (56.4%) met step 1 of the cascade (≥2 signs and symptoms suggestive of TB). Step 2(further screening of history of TB contact/full respiratory exam) was documented in 14,873/23,741 (62.6%) who met Step 1. Step 3(chest x-ray or Mantoux test) was requested in 2,451/14,873 (16.5%) who met Step 2. Step 4(≥1 bacteriological test) was requested in 392/2,451 (15.9%) who met Step 3. Step 5("Working TB" diagnosis) was documented in 175/392 (44.6%) who met Step 4. Factors associated with request of TB tests in patients who met Step 1 included: i) older children [AOR 1.19(CI 1.09-1.31)]; ii) co-morbidities of HIV, malnutrition or pneumonia [AOR 3.81(CI 3.05-4.75), 2.98(CI 2.69-3.31) and 2.98(CI 2.60-3.40) respectively]; iii) sicker children, readmitted/referred [AOR 1.24(CI 1.08-1.42) and 1.15(CI 1.04-1.28) respectively]. "Working TB" diagnosis was made in 2.9%(1,202/42,107) of all admissions and 0.2%(89/42,107) were bacteriologically-confirmed. CONCLUSIONS:More than half of all paediatric admissions had symptoms associated with TB and nearly two-thirds had more specific history documented. Only a few amongst them got TB tests requested. TB was diagnosed in 2.9% of all admissions but most were inadequately investigated. Major challenges remain in identifying and investigating TB in children in hospitals with access to Xpert MTB/RIF and a review is needed of existing guidelines