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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.

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:BackgroundDrug-resistant tuberculosis continues to be a global public health threat. Ethiopia is one of the high-burden countries for tuberculosis and multi-drug resistant tuberculosis. The estimated annual incidents of tuberculosis were 119 per 100,000 populations in 2021 and the prevalence of multi-drug resistance tuberculosis is about 0.7% among newly diagnosed cases in Ethiopia. On time detection of rifampicin resistance is essential for the management of the disease and earlier treatment initiation. Among the different diagnostic tests; Xpert is widely used for the rapid detection of Mycobacterium tuberculosis and rifampicin resistant in the country. The prevalence of rifampicin resistance-pulmonary tuberculosis varied from locality to locality and the estimated national prevalence of rifampicin resistance pulmonary tuberculosis is not available in the country. Therefore, the aim of this meta-analysis was to summarize the results of available studies and generate pooled prevalence estimate of rifampicin resistance pulmonary tuberculosis in Ethiopia.MethodsLiterature search was carried out using PubMed and Scopus public databases. Original articles conducted in Ethiopia and those containing a prevalence report of rifampicin resistance pulmonary tuberculosis diagnosed by Xpert Mycobacterium tuberculosis/rifampicin resistance assay were included in the meta-analysis. All retrospective and prospective studies published until May 2022 were screened in the study. The methodological qualities of included article were assessed using Joanna Briggs Institute quality assessment tool for cross-sectional studies. Random effect model was used to determine the pooled prevalence of rifampicin resistance pulmonary tuberculosis. Subgroup analysis and regression were carried out across regional states and study designs. Heterogeneity across studies was assessed using I2 test. The data were analyzed using STATA version 14.ResultA total of 1570 titles were identified and 34 studies met the inclusion criteria. Of the total 17,292 pulmonary tuberculosis patients who were identified from the included articles, 1669 were rifampicin resistance pulmonary tuberculosis. The pooled prevalence of rifampicin resistant among pulmonary tuberculosis patients diagnosed with Xpert Mycobacterium tuberculosis/rifampicin resistance assay was 9.67% (95% CI: 8.11-11.24). The highest pooled prevalence was from Oromia11.84% (95% CI: 4.49-19.2%) and the lowest rifampicin resistance was identified in Amhara Regional State, 8.51% (95% CI: 5.96-11.06%). The pooled prevalence rates of rifampicin resistant among pulmonary tuberculosis patients were 10.18% (95% CI: 6.85-13.51) and 9.57% (95% CI: 7.68-11.47) in prospective and retrospective types of cross-sectional studies.ConclusionOur study showed that the pooled prevalence of rifampicin resistance among pulmonary tuberculosis patients was 9.67%. This showed that the occurrence of rifampicin resistance pulmonary tuberculosis among Mycobacterium tuberculosis patients remains high in Ethiopia. Regional state wise, rifampicin resistance variation was small. Further meta-analysis of factors associated with rifampicin resistance among pulmonary tuberculosis patients as well as among extrapulmonary Mycobacterium tuberculosis cases should be carried out.

Project description:The objective of this prospective observational study carried out at China-Uganda Friendship Hospital-Naguru in Kampala, Uganda, was to determine the performance of GeneXpert MTB/RIF Ultra (Xpert Ultra) molecular testing on saliva for active tuberculosis (TB) disease among consecutive adults undergoing TB diagnostic evaluation who were Xpert Ultra positive on sputum. We calculated sensitivity to determine TB diagnostic performance in comparison to a composite reference standard of Mycobacterium tuberculosis liquid and solid cultures on two spot sputum specimens. Xpert Ultra on a single saliva sample had a sensitivity of 90% (95% confidence interval [CI], 81 to 95%) relative to the composite sputum culture-based reference standard, similar to the composite sensitivity of 87% (95% CI, 77 to 94%) for fluorescence microscopy (FM) for acid-fast bacilli on two sputum smears. The sensitivity of salivary Xpert Ultra was 24% lower (95% CI for difference, 2 to 48%; P = 0.003) among persons living with HIV (71%; 95% CI, 44 to 90%) than among persons living without HIV (95%; 95% CI, 86 to 99%) and 46% higher (95% CI, 14 to 77%; P < 0.0001) among FM-positive (96%; 95% CI, 87 to 99%) than among FM-negative (50%; 95% CI, 19 to 81%) patients. The semiquantitative Xpert Ultra grade was systematically higher in sputum than in a paired saliva sample from the same patient. In conclusion, molecular testing of saliva for active TB diagnosis was feasible and almost as sensitive as molecular testing of sputum in a high TB burden setting. IMPORTANCE Tuberculosis is among the leading causes of morbidity and mortality worldwide, in large part because >3 million people go undiagnosed and untreated each year. Sputum has been the mainstay for TB diagnosis for over a century but can be difficult for patients to produce. In addition, the vigorous coughing required during sputum collection can lead to infection of nearby individuals and health workers. In this case-only study, applying the ultra-sensitive GeneXpert MTB/RIF Ultra molecular diagnostic assay to saliva detected 90% of culture-confirmed TB cases among 81 adults who were undergoing TB evaluation at the outpatient department of a general hospital in Uganda and tested sputum GeneXpert MTB/RIF Ultra positive. These results suggest that saliva may be a feasible and sensitive alternative to sputum for TB diagnosis, thereby meeting two key metrics proposed by the World Health Organization in its target performance profile for a nonsputum test for TB.

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.

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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