Anti-Tuberculosis Drug Resistance among New and Previously Treated Sputum Smear-Positive Tuberculosis Patients in Uganda: Results of the First National Survey

Lukoye, Deus; Adatu, Francis; Musisi, Kenneth; Kasule, George William; Were, Willy; Odeke, R; Kalamya, Julius N; Awor, Ann; Date, Anand; Joloba, Moses

doi:10.1371/journal.pone.0070763

Cited by 73 publications

(92 citation statements)

References 17 publications

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“…However, estimates of primary resistance to isoniazid in HIV-infected individuals in all three trial settings were low, ranging from 3.8% in Soweto (6), 7.5% in Nairobi (34), and 4-9% in Uganda (35,36), and unlikely to affect our results. A recent national drug resistance survey in Uganda found that primary isoniazid resistance has remained low at 5% (37). It is also possible that IPT may lead to the selection of isoniazid resistance in individuals undergoing treatment; however, there appears to be no evidence of this in the included trials.…”

Section: Discussionmentioning

confidence: 99%

Ability of preventive therapy to cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-burden settings

Houben¹,

Sumner²,

Grant

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Trials of isoniazid preventive therapy (IPT) for people living with HIV in southern Africa have shown high rates of tuberculosis disease immediately after cessation of therapy. This could be due to the lack of cure following preventive therapy or reinfection with rapid progression to disease. Using a model fitted to trial data, we estimate the degree to which preventive therapies cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-tuberculosis-burden settings. We identified randomized controlled trials that compared IPT to placebo or alternative regimen in HIV-positive, tuberculin skin test positive individuals. A mathematical model describing tuberculosis transmission in a closed cohort of HIV-positive, M. tuberculosis infected, antiretroviral therapy naive individuals following completion of preventive therapy (or placebo) was fitted to posttherapy tuberculosis rates to estimate the annual risk of M. tuberculosis reinfection and the proportion of individuals whose latent infection was cured after therapy. Three trials met our inclusion criteria. Estimated annual risks of reinfection ranged between 3.7 and 4.9%. Our results suggest 6 mo of isoniazid cured in a small proportion [estimated proportion cured = 0% (interquartile range 0-30.9%)]. The proportion cured for 3-mo regimens containing rifampicin or rifapentine was 19-100%. IPT alone does not cure existing infections in the majority of HIV-infected individuals. In high-incidence settings, continuous IPT should be integrated with HIV care. Where the risk of reinfection is lower, preventive therapy with more curative drugs should be preferred for HIV-positive individuals to achieve durable patient benefit.

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Section: Discussionmentioning

confidence: 99%

Ability of preventive therapy to cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-burden settings

Houben¹,

Sumner²,

Grant

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Besides, extensively drug resistant TB (XDR-TB) has been reported by 92 countries (including Kenya) and about 10.6% of MDR TB patients have XDRTB globally. Therefore, the rapid spread of MDRTB and XDRTB especially in new TB patients is challenging the effectiveness of TB control programmes in many low income countries [8] [9]. cases is vital in the assessment of the effectiveness of national TB control progrmmme [10].…”

Section: Introductionmentioning

confidence: 99%

Drug Susceptibility Patterns of Mycobacterium tuberculosis Isolates from Tuberculosis Patients in Coastal Kenya

Yonge¹,

Otieno²,

Sharma³

et al. 2017

JTR

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Background: Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis. Anti-tuberculosis drug resistance is an emerging health problem in Kenya and especially in Coastal region. This is a major challenge in tuberculosis control. Diagnosis is based on Ziel-Neelsen staining alone and patients are treated without information on sensitivity patterns.Aim: This study aimed to determine drug susceptibility patterns of Mycobacterium tuberculosis in Coastal Kenya. Study Design: Hospital and laboratory based cross-sectional study was carried between April 2015 and July 2016 at Coast General Referral hospital; Tudor, Port-Reitz, Likoni Sub-County hospitals; Mlaleo, Kongowea and Mikindani health centers. Methodology: Sputum samples from patients with bacteriological confirmed TB on microscopy were cultured on Lowenstein Jensen (LJ) media. Strains of MTB complex from Lowenstein Jensen (LJ) slopes were subjected to drug susceptibility testing (DST) to first-line drugs including isoniazid (H), rifampicin (R), streptomycin (S) and Ethambutol (E) using proportional method on the Mycobacterium Growth Indicator Tube (MGIT) conventional method. Participants were offered diagnostic testing and counselling for HIV testing. Results: Drug sensitivity test was performed for a total of 210 Mycobacterium tuberculosis isolates for the first line anti-TB drugs. About seventy eight percent and twenty nine percent of the strains from new patients and previously treated patients were fully sensitive to all the drugs tested respectively. Prevalence of any resistance to one drug was 102 (48.6%, 95% CI: 20.45 -28.23). Any single drug resistance was most frequent in isoniazid 30 (16.0%), Ethambutol 20 (10.0%), Streptomycin 18 (18.3%) and Rifampicin 4 (2.1%) in newly diagnosed patients. Among previously treated patients any resistance to streptomycin, ethambutol, isoniaziad and rifampicin was 10 (58.8%), 9 (52.9%), 7 (41.2%) and 4 (23.5%) respectively. Prevalence of MDR-TB defined as resistant to at least both isoniazid and rifampicin was 10 (4.8%) among new and previously treated patients respectively. Conclusion: The current study reveals that the overall resistance to first line anti-TB drugs was high. Although the rate of MDR-TB was relatively low, this signifies that conditions favouring the spread of MDR-TB are on high rise. Therefore, it is essential to address the problems of development of drug resistant strains of TB by establishing good TB programmes (DOTS). Patients' adherence to anti-TB drugs and introducing drug sensitivity testing (DST) services at County level hospitals will minimize occurrence of drug resistant.

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“…Anti-TB drug resistance levels in Uganda are low, with any resistance to anti-TB drugs estimated at 10.3% among new cases and 25.9% among the previously treated, while multidrug-resistant TB (MDR-TB) prevalence is 1.4% and 12.1%, respectively (13). About 53% of all TB patients in Uganda are coinfected with HIV (12), while at population level the HIV prevalence rate is 7.3% in the 15-to 49-year age group (14).…”

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confidence: 99%

The T2 Mycobacterium tuberculosis Genotype, Predominant in Kampala, Uganda, Shows Negative Correlation with Antituberculosis Drug Resistance

Lukoye¹,

Katabazi²,

Musisi³

et al. 2014

Antimicrob Agents Chemother

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e Surveillance of the circulating Mycobacterium tuberculosis complex (MTC) strains in a given locality is important for understanding tuberculosis (TB) epidemiology. We performed molecular epidemiological studies on sputum smear-positive isolates that were collected for anti-TB drug resistance surveillance to establish the variability of MTC lineages with anti-TB drug resistance and HIV infection. Spoligotyping was performed to determine MTC phylogenetic lineages. We compared patients' MTC lineages with drug susceptibility testing (DST) patterns and HIV serostatus. , 5.0; 95% CI, 2.0 to 11.9; P < 0.001) and CAS (OR adj , 2.9; 95% CI, 1.4.0 to 6.3; P ‫؍‬ 0.006) families were more likely to show any resistance than was T2. All other MTC lineages combined were more likely to be resistant to any of the anti-TB drugs than were the T2 strains (OR adj , 1.7; 95% CI, 1.0 to 2.9; P ‫؍‬ 0.040). There were no significant associations between multidrug resistance and MTC lineages, but numbers of multidrug-resistant TB strains were small. No association was established between MTC lineages and HIV status. In conclusion, the T2 MTC lineage negatively correlates with anti-TB drug resistance, which might partly explain the reported low levels of anti-TB drug resistance in Kampala, Uganda. Patients' HIV status plays no role with respect to the MTC lineage distribution.

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Anti-Tuberculosis Drug Resistance among New and Previously Treated Sputum Smear-Positive Tuberculosis Patients in Uganda: Results of the First National Survey

Cited by 73 publications

References 17 publications

Ability of preventive therapy to cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-burden settings

Ability of preventive therapy to cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-burden settings

Drug Susceptibility Patterns of Mycobacterium tuberculosis Isolates from Tuberculosis Patients in Coastal Kenya

The T2 Mycobacterium tuberculosis Genotype, Predominant in Kampala, Uganda, Shows Negative Correlation with Antituberculosis Drug Resistance

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