Validation of the GenoType® MTBDRplus assay for detection of MDR-TB in a public health laboratory in Thailand

<p>Abstract</p> <p>Background</p> <p>Over the past several years, new diagnostic techniques have been developed to allow for the rapid detection of multidrug resistant tuberculosis. The GenoType^®MTBDR<it>plus </it>test is a deoxyribonucleic acid (DNA) strip assay which uses polymerase chain reaction (PCR) and hybridization to detect genetic mutations in the genes that confer isoniazid (INH) and rifampn (RIF) resistance. This assay has demonstrated good performance and a rapid time to results, making this a promising tool to accelerate MDR-TB diagnosis and improve MDR-TB control. Validation of rapid tests for MDR-TB detection in different settings is needed to ensure acceptable performance, particularly in Asia, which has the largest number of MDR-TB cases in the world but only one previous report, in Vietnam, about the performance of the GenoType^®MDR<it>plus </it>assay. Thailand is ranked 18^thof 22 "high-burden" TB countries in the world, and there is evidence to suggest that rates of MDR-TB are increasing in Thailand. We compared the performance of the GenoType^®MTBDR<it>plus </it>assay to Mycobacterial Growth Indicator Tube for Antimycobacterial Susceptibility Testing (MGIT AST) for detection INH resistance, RIF resistance, and MDR-TB in stored acid-fast bacilli (AFB)-positive sputum specimens and isolates at a Public TB laboratory in Bangkok, Thailand.</p> <p>Methods</p> <p>50 stored isolates and 164 stored AFB-positive sputum specimens were tested using both the MGIT AST and the GenoType^®MTBDR<it>plus </it>assay.</p> <p>Results</p> <p>The GenoType^®MTBDR<it>plus </it>assay had a sensitivity of 95.3%, 100%, and 94.4% for INH resistance, RIF resistance, and MDR-TB, respectively. The difference in sensitivity between sputum specimens (93%) and isolates (100%) for INH resistance was not statistically significant (p = 0.08). Specificity was 100% for all resistance patterns and for both specimens and isolates. The laboratory processing time was a median of 25 days for MGIT AST and 5 days for the GenoType^®MTBDR<it>plus </it>(p < 0.01).</p> <p>Conclusion</p> <p>The GenoType^®MTBDR<it>plus </it>assay has been validated as a rapid and reliable first-line diagnostic test on AFB-positive sputum or MTB isolates for INH resistance, RIF resistance, and MDR-TB in Bangkok, Thailand. Further studies are needed to evaluate its impact on treatment outcome and the feasibility and cost associated with widespread implementation.</p

Evaluation of adherence to national treatment guidelines among tuberculosis patients in three provinces of South Africa

Setting. Standardised tuberculosis (TB) treatment through directly observed therapy (DOT) is available in South Africa, but the level of adherence to standardised TB treatment and its impact on treatment outcomes is unknown.Objectives. To describe adherence to standardised TB treatment and provision of DOT, and analyse its impact on treatment outcome.Methods. We utilised data collected for an evaluation of the South African national TB surveillance system. A treatment regimen was considered appropriate if based on national treatment guidelines. Multivariate log-binomial regression was used to evaluate the association between treatment regimens, including DOT provision, and treatment outcome.Results. Of 1 339 TB cases in the parent evaluation, 598 (44.7%) were excluded from analysis owing to missing outcome or treatment information. The majority (697, 94.1%) of the remaining 741 patients received an appropriate TB regimen. Almost all patients (717, 96.8%) received DOT, 443 (59.8%) throughout the treatment course and 274 (37.0%) during the intensive (256, 34.6%) or continuation (18, 2.4%) phase. Independent predictors of poor outcome were partial DOT (adjusted risk ratio (aRR) 3.1, 95% confidence interval (CI) 2.2 - 4.3) and previous treatment default (aRR 2.3, 95% CI 1.1 - 4.8).Conclusion. Patients who received incomplete DOT or had a history of defaulting from TB treatment had an increased risk of poor outcomes

Patterns of treatment interruption among patients with multidrug-resistant TB (MDR TB) and association with interim and final treatment outcomes.

BACKGROUND: The reasons that patients with multidrug-resistant tuberculosis (MDR TB) miss treatment are multi-factorial and complex. Identifying patterns of treatment interruption that predict poor outcomes can be used to target program activities aiming to improve treatment adherence. OBJECTIVE: To characterize patterns of treatment interruption among MDR TB patients and determine the association between patterns and treatment outcomes. METHODS: Retrospective analysis of MDR TB patients. A treatment interruption was defined as any time that a patient missed a prescribed dose of treatment for at least 1 day but for a period of less than 2 consecutive months. Patients were characterized by the number, length and variability of interruptions, variability of time between interruptions, and percent of missed doses. Final treatment outcome was dichotomized as a successful (cured or completed) or poor outcome (defaulted, failed, or died). Risk ratios were calculated to determine the association between characteristics of treatment interruption and treatment outcomes. All analyses were conducted in 6 month treatment intervals. RESULTS: Only 7.0% of 583 patients completed treatment without interruption. Of the remaining 542 patients, the median time to the first interruption was 2 ½ months (70 days). In multivariate analysis, patients who had longer interruptions with sporadic variability during the 6-12 month or the 12-18 month treatment period had a significantly increased risk for poor outcomes compared to patients who had short, regular interruptions (RR(adj) 4.37, 95% CI 1.2-15.8;  = 0.03 and RR(adj) 3.38, 95% CI 1.6-7.1; p = 0.001, respectively). In addition, missing 10% or more of the prescribed doses during any 6 month period in the initial 18 months of therapy significantly increased the risk for poor outcomes (RR(adj) range 1.55-2.35; p-value range 0.01-0.005). CONCLUSION: Patients that miss more consecutive days of treatment with sporadic interruption patterns or a greater proportion of treatment are at an increased risk for poor treatment outcomes

Economic costs of rotavirus gastroenteritis and cost-effectiveness of vaccination in developing countries.

BACKGROUND: Rotavirus is the leading cause of severe gastroenteritis in children worldwide. We evaluated the economic burden of rotavirus and the cost-effectiveness of vaccination from the health care perspective. METHODS: Estimates were based on existing epidemiological data, cost estimates, vaccine coverage, and efficacy data, as well as hypothetical vaccine prices. Outcome measures included health care and societal costs of rotavirus and benefits and incremental cost-effectiveness ratio of vaccination. Sensitivity analyses evaluated the impact of estimate uncertainty. RESULTS: Treatment costs increased with income level, and health burden decreased; however, burden varied across regions. On the basis of current vaccination coverage and timing, rotavirus vaccination would annually prevent 228,000 deaths, 13.7 million hospital visits, and 8.7 million disability-adjusted life-years, saving $188 million in treatment costs and$243 million in societal costs. At $5 per dose, the incremental cost-effectiveness ratio in low-, lower-middle-, and upper-middle-income countries was$88, $291, and$329 per disability-adjusted life-year averted, respectively, and $3,015,$9,951 and $11,296 per life saved, respectively. Vaccination would prevent approximately 45% of deaths and approximately 58% of associated medical visits and costs. CONCLUSIONS: Vaccination is a cost-effective strategy to reduce the health and economic burden of rotavirus. The cost-effectiveness of vaccination depends mostly on vaccine price and reaching children at highest risk of mortality

Multivariate association between treatment interruption pattern characteristics for each 6 month treatment period and poor treatment outcomes (default, failure, death) among MDR TB patients with at least one missed dose during the course of treatment (n = 542).

<p>RR, rate ratio; CI, confidence interval.</p>*<p>Each variable represents characteristic for the 6 month treatment period (e.g., 0–6 months).</p>†<p>All RRs adjusted for age, number of treatment interruptions, variability of time on treatment, and whether they were underweight (BMI<18), or received kanamycin/amikacin or clarithromycin during the treatment period. RRs presented are adjusted for all other variables in the model. Dashes (–) for RR and 95% CI indicate there were not enough observations in the interruption category for that time period to derive an estimate.</p

Treatment patterns among MDR TB patients, by 6 month intervals of treatment (n = 583).

<p>Four categories of treatment interruption patterns based on the patients in the period that had at least one treatment interruption (missed dose) during that period. Cut-offs to create categories based on the median of interruption characteristics (individual mean interruption length in days and the individual standard deviation of the interruption length in days) during the period, wherein individual values below and inclusive of the median value denoted short or small/regular and values exceeding the median cut-off were categorized as long or large/sporadic. The pooled median of individual mean days of interruption and standard deviation of interruption used for cut-offs was 1.14, 0 for 0–6 months; 1.21, 0.38 for 6–12 months; 1.28, 0.50 for 12–18 months, and 1.33, 0.51 for 18–24 months. N in parentheses at the top of each column reflects number of patients who were still on treatment at the beginning of the 6 month period.</p

Illustration of 4 different treatment interruption categories, based on length of interruption in days (short or long), and variability of interruption (small/regular or long/sporadic).

<p>Y-axis indicates treatment interruption as 0 (no; on treatment) or 1 (yes; interruption/missed dose).</p