Dataset Information

Surveillance for multi-drug and rifampicin resistant tuberculosis and treatment outcomes among previously treated persons with tuberculosis in the era of GeneXpert in rural eastern Uganda.

ABSTRACT: Rationale:Previously treated persons with bacteriologically confirmed pulmonary tuberculosis (BC-PTB) have increased risk of developing multi-drug resistant or rifampicin resistant tuberculosis (MDR/RR-TB). Surveillance for resistance is critical to identify and treat MDR/RR-TB to ensure cure and prevent transmission. There are limited studies conducted on this subject. Objectives:We examined the frequency and factors associated with MDR/RR-TB surveillance among previously treated persons with BC-PTB, and described their treatment outcomes in rural eastern Uganda. Methods:We reviewed treatment records for BC-PTB between January 2015 and June 2018 at 10 clinics in eastern Uganda. We collected data on demographics, surveillance for MDR/RR, use of GeneXpert and treatment outcomes. We performed bivariate and multivariate analyses. For multivariate analysis, we used the modified Poisson regression analysis with robust standard errors and stated the results as adjusted risk ratio (aRR) with 95% confidence intervals (CI). All analyses were conducted in R version 3.5.2. Measurements and main results:We obtained records for 135 previously treated persons with BC-PTB and of these, 41 (30.4%) had undergone surveillance for MDR/RR-TB. Treatment failures were less likely to have surveillance compared to relapses (aRR, 0.28; 95% CI, 0.08-0.95), and there was an increasing trend in the likelihood for surveillance between 2015 and 2018 (aRR, 1.77; 95% CI, 1.39-2.25). There was no difference in MDR/RR-TB surveillance rate between health facilities with and without GeneXpert on-site (aRR, 1.52; 95% CI, 0.81-2.86) and between male and female patients (aRR, 0.54; 95% CI, 0.21-1.37). Overall, 92 (68.1%) previously treated persons with BC-PTB were successfully treated for tuberculosis. Conclusions:MDR/RR-TB surveillance and treatment success rates among previously treated persons with BC-PTB in rural eastern Uganda are low. Tuberculosis programs should strengthen MDR/RR-TB surveillance and especially target those with treatment failure.

SUBMITTER: Izudi J

PROVIDER: S-EPMC7038458 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Surveillance for multi-drug and rifampicin resistant tuberculosis and treatment outcomes among previously treated persons with tuberculosis in the era of GeneXpert in rural eastern Uganda.

Izudi Jonathan J Tamwesigire Imelda K IK Bajunirwe Francis F

Journal of clinical tuberculosis and other mycobacterial diseases 20200213

<h4>Rationale</h4>Previously treated persons with bacteriologically confirmed pulmonary tuberculosis (BC-PTB) have increased risk of developing multi-drug resistant or rifampicin resistant tuberculosis (MDR/RR-TB). Surveillance for resistance is critical to identify and treat MDR/RR-TB to ensure cure and prevent transmission. There are limited studies conducted on this subject.<h4>Objectives</h4>We examined the frequency and factors associated with MDR/RR-TB surveillance among previously treated ...[more]

PMID: 32123755

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Project description:BackgroundDrug-resistant tuberculosis (DR-TB), including rifampicin-resistant tuberculosis (RR-TB) and multidrug-resistant tuberculosis (MDR-TB, or RR-TB with additional isoniazid resistance), presents challenges to TB control. In Uganda, the GeneXpert test provides point-of-care testing for TB and rifampicin resistance. Patients identified with RR-TB receive culture-based drug susceptibility testing (DST) to identify additional resistance, if any. There are few data on the epidemiological profiles of current DR-TB patients in Uganda. We described patients with RR-TB in Uganda and assessed the trends of RR-TB to inform TB control interventions.MethodsWe identified patients with RR-TB whose samples were referred for culture and DST during 2014-2018 from routinely-generated laboratory surveillance data at the Uganda National Tuberculosis Reference Laboratory. Data on patient demographics and drug sensitivity profile of Mycobacterium tuberculosis isolates were abstracted. Population data were obtained from the Uganda Bureau of Statistics to calculate incidence. Descriptive epidemiology was performed, and logistic regression used to assess trends.ResultsWe identified 1474 patients whose mean age was 36 ± 17 years. Overall incidence was 3.8/100,000 population. Males were more affected by RR-TB than females (4.9 vs. 2.7/100,000, p ≤ 0.01). Geographically, Northern Uganda was the most affected region (IR = 6.9/100,000) followed by the Central region (IR = 5.01/100,000). The overall population incidence of RR-TB increased by 20% over the evaluation period (OR = 1.2; 95% CI 1.15-1.23); RR-TB in new TB cases increased by 35% (OR = 1.35; 95% CI 1.3-1.4) and by 7% in previously-treated cases (OR = 1.07; 95% CI 1.0-1.1). Of the 1474 patients with RR-TB, 923 (63%) were culture-positive of whom 670 (72%) had full DST available. Based on the DST results, 522/670 (78%) had MDR-TB.ConclusionBetween 2014 and 2018, the incidence of RR-TB increased especially among newly-diagnosed TB patients. We recommend intensified efforts and screening for early diagnosis especially among previously treated patients. Mechanisms should be in put to ensure that all patients with RR-TB obtain DST.

Project description:Resistance to anti-tuberculosis drugs is a serious public health problem. Multi-drug resistant tuberculosis (MDR-TB), defined as resistance to at least rifampicin and isoniazid, has been reported in all regions of the world. Current phenotypic methods of assessing drug susceptibility of M. tuberculosis are slow. Rapid molecular methods to detect resistance to rifampicin have been developed but they are not affordable in some high prevalence countries such as those in sub Saharan Africa. A simple multi-well plate assay using mycobacteriophage D29 has been developed to test M. tuberculosis isolates for resistance to rifampicin. The purpose of this study was to investigate the performance of this technology in Kampala, Uganda.In a blinded study 149 M. tuberculosis isolates were tested for resistance to rifampicin by the phage assay and results compared to those from routine phenotypic testing in BACTEC 460. Three concentrations of drug were used 2, 4 and 10 microg/ml. Isolates found resistant by either assay were subjected to sequence analysis of a 81 bp fragment of the rpoB gene to identify mutations predictive of resistance. Four isolates with discrepant phage and BACTEC results were tested in a second phenotypic assay to determine minimal inhibitory concentrations.Initial analysis suggested a sensitivity and specificity of 100% and 96.5% respectively for the phage assay used at 4 and 10 microg/ml when compared to the BACTEC 460. However, further analysis revealed 4 false negative results from the BACTEC 460 and the phage assay proved the more sensitive and specific of the two tests. Of the 39 isolates found resistant by the phage assay 38 (97.4%) were found to have mutations predictive of resistance in the 81 bp region of the rpoB gene. When used at 2 mug/ml false resistant results were observed from the phage assay. The cost of reagents for testing each isolate was estimated to be 1.3 US dollars when testing a batch of 20 isolates on a single 96 well plate. Results were obtained in 48 hours.The phage assay can be used for screening of isolates for resistance to rifampicin, with high sensitivity and specificity in Uganda. The test may be useful in poorly resourced laboratories as a rapid screen to differentiate between rifampicin susceptible and potential MDR-TB cases.

Project description:BackgroundIntroduction of GeneXpert MTB/RIF (Xpert) assay has constituted a major breakthrough for tuberculosis (TB) diagnostics. Several patient factors may influence diagnostic performance of Xpert including sputum quality.ObjectiveWe carried out a prospective, observational, cross-sectional study to determine the effect of sputum quality on diagnostic performance of Xpert among presumed TB patients in Uganda.MethodsWe collected clinical and demographic information and two sputum samples from participants. Staff recorded sputum quality and performed LED fluorescence microscopy and mycobacterial culture on each sample. If both smear examinations were negative, Xpert testing was performed. We calculated diagnostic yield, sensitivity, specificity, and other indicators for Xpert for each stratum of sputum quality in reference to a standard of mycobacterial culture.ResultsPatients with salivary sputum showed a trend towards a substantially higher proportion of samples that were Xpert-positive (54/286, 19%, 95% CI 15-24) compared with those with all other sputum sample types (221/1496, 15%, 95% CI 13-17). Blood-stained sputum produced the lowest sensitivity (28%; 95% CI 12-49) and salivary sputum the highest (66%; 95% CI 53-77). Specificity didn't vary meaningfully by sample types. Salivary sputum was significantly more sensitive than mucoid sputum (+13%, 95% CI +1 to +26), while blood-stained sputum was significantly less sensitive (-24%, 95% CI -42 to -5).ConclusionsOur findings demonstrate the need to exercise caution in collecting sputum for Xpert and in interpreting results because sputum quality may impact test yield and sensitivity. In particular, it may be wise to pursue additional testing should blood-stained sputum test negative while salivary sputum should be readily accepted for Xpert testing given its higher sensitivity and potentially higher yield than other sample types. These findings challenge conventional recommendations against collecting salivary sputum for TB diagnosis and could inform new standards for sputum quality.

Dataset Information

Surveillance for multi-drug and rifampicin resistant tuberculosis and treatment outcomes among previously treated persons with tuberculosis in the era of GeneXpert in rural eastern Uganda.

Publications

Surveillance for multi-drug and rifampicin resistant tuberculosis and treatment outcomes among previously treated persons with tuberculosis in the era of GeneXpert in rural eastern Uganda.

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