Treatment outcomes of drug resistant tuberculosis patients with multiple poor prognostic indicators in Uganda: A countrywide 5-year retrospective study

Baluku, Joseph Baruch; Nakazibwe, Bridget; Naloka, Joshua; Nabwana, Martin; Mwanja, Sarah; Mulwana, Rose; Sempiira, Mike; Nassozi, Sylvia; Babirye, Febronius; Namugenyi, Carol; Ntambi, Samuel; Namiiro, Sharon; Bongomin, Felix; Katuramu, Richard; Andia-Biraro, Irene; Worodria, William

doi:10.1016/j.jctube.2021.100221

Cited by 28 publications

(33 citation statements)

References 31 publications

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“…It is worth noting that DRTB treatment success in Uganda was 74% in the 2017 cohort, which was way above the global estimate of 57% (World Health Organization, 2020) and therefore, it is not surprising that pregnant women with DRTB in Uganda also had a higher rate of treatment success. Additionally, while there was a high prevalence of HIV among pregnant women in our study, the proportion is lower than the 53%-59% reported among nationwide DRTB cohorts whose treatment success rate was >70% (Baluku et al, 2021;Kasozi et al, 2020). Even among people with TB/HIV co-infection in Uganda, regardless of pregnancy status, the treatment success rate is 74% (Musaazi et al, 2017).…”

Section: Discussioncontrasting

confidence: 74%

“…This was part of a larger countrywide retrospective review of patients' charts from 16 of 17 DRTB treatment sites in Uganda (Baluku et al, 2021). In this study, eligible patients were all pregnant women with laboratory-confirmed DRTB who had a documented treatment outcome between 2013 and 2019.…”

Section: Study Setting and Populationmentioning

confidence: 99%

“…Women were monitored monthly for clinical improvement (signs and symptoms), sputum conversion (sputum cultures) and side effects (serum creatinine, liver transaminases, full haemogram and audiometry). Further details of DRTB management in Uganda are described elsewhere (Baluku et al, 2021;Kasozi et al, 2020).…”

Section: Diagnosis and Management Of Drtb Among Pregnant Womenmentioning

confidence: 99%

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Treatment outcomes of pregnant women with drug-resistant tuberculosis in Uganda: A retrospective review of 18 cases

Baluku

Bongomin

2021

International Journal of Infectious Diseases

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Background: There is a dearth of reports on drug-resistant tuberculosis (DRTB) treatment outcomes among pregnant women in tuberculosis (TB)/HIV high-burdened countries. We report treatment outcomes of 18 pregnant women with DRTB in Uganda. Methods: We reviewed charts of individuals who received DRTB treatment in Uganda across 16 DRTB treatment sites. We included all women who were pregnant during DRTB treatment and had a treatment outcome documented between 2013 and 2019. Results: There were 18 pregnant women with a mean age (standard deviation (SD)) of 27.5 (5.2) years, of whom 8 (44.4%) were HIV co-infected. Among these women, 12 (66.7%) had primary DRTB and 8 (44.4%) had multidrug-resistant TB. Levofloxacin (Lfx), Pyrazinamide, Cycloserine and Kanamycin (Kn) were the most (>78%) used drugs in the treatment regimen and the mean (SD) treatment duration was 17.6 (7.5) months. Elevated liver enzymes (81.8%, n = 11) and hearing loss (33.3%, n = 15) were the most frequently encountered drug adverse events. Treatment success was observed among 15 (83.3%) patients, 2 (11.1%) patients were lost to follow up and 1 (5.6%) patient died. Conclusion:The treatment success among pregnant women with DRTB in Uganda was high despite a high prevalence of HIV co-infection.

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Section: Discussioncontrasting

confidence: 74%

Section: Study Setting and Populationmentioning

confidence: 99%

Section: Diagnosis and Management Of Drtb Among Pregnant Womenmentioning

confidence: 99%

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Treatment outcomes of pregnant women with drug-resistant tuberculosis in Uganda: A retrospective review of 18 cases

Baluku

Bongomin

2021

International Journal of Infectious Diseases

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“…We conducted secondary analysis of data from a nationwide retrospective cohort [ 20 ] of DR-TB patients with poor prognostic indicators who had laboratory confirmed DR-TB and a treatment outcome documented between January 2013 and December 2019. We extracted data for patients reviewed by the national DR-TB consilium during the same period.…”

Section: Methodsmentioning

confidence: 99%

“…In this study, we describe characteristics and treatment outcomes of DR-TB cases presented to the national DR-TB consilium in Uganda drawn from a large nationwide cohort [ 20 ] of patients with poor prognostic indicators, of whom 59% were HIV co-infected.…”

Section: Introductionmentioning

confidence: 99%

Multidisciplinary management of difficult-to-treat drug resistant tuberculosis: a review of cases presented to the national consilium in Uganda

et al. 2021

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Background Patients with drug resistant tuberculosis (DR-TB) with comorbidities and drug toxicities are difficult to treat. Guidelines recommend such patients to be managed in consultation with a multidisciplinary team of experts (the “TB consilium”) to optimise treatment regimens. We describe characteristics and treatment outcomes of DR-TB cases presented to the national DR-TB consilium in Uganda between 2013 and 2019. Methods We performed a secondary analysis of data from a nation-wide retrospective cohort of DR-TB patients with poor prognostic indicators in Uganda. Patients had a treatment outcome documented between 2013 and 2019. Characteristics and treatment outcomes were compared between cases reviewed by the consilium with those that were not reviewed. Results Of 1,122 DR-TB cases, 189 (16.8%) cases from 16 treatment sites were reviewed by the consilium, of whom 86 (45.5%) were reviewed more than once. The most frequent inquiries (N = 308) from DR-TB treatment sites were construction of a treatment regimen (38.6%) and management of side effects (24.0%) while the most frequent consilium recommendations (N = 408) were a DR-TB regimen (21.7%) and “observation while on current regimen” (16.6%). Among the cases reviewed, 152 (80.4%) were from facilities other than the national referral hospital, 113 (61.1%) were aged ≥ 35 years, 72 (40.9%) were unemployed, and 26 (31.0%) had defaulted antiretroviral therapy. Additionally, 141 (90.4%) had hepatic injury, 55 (91.7%) had bilateral hearing loss, 20 (4.8%) had psychiatric symptoms and 14 (17.7%) had abnormal baseline systolic blood pressure. Resistance to second-line drugs (SLDs) was observed among 9 (4.8%) cases while 13 (6.9%) cases had previous exposure to SLDs. Bedaquiline (13.2%, n = 25), clofazimine (28.6%, n = 54), high-dose isoniazid (22.8%, n = 43) and linezolid (6.7%, n = 13) were more frequently prescribed among cases reviewed by the consilium than those not reviewed. Treatment success was observed among 126 (66.7%) cases reviewed. Conclusion Cases reviewed by the consilium had several comorbidities, drug toxicities and a low treatment success rate. Consilia are important “gatekeepers” for new and repurposed drugs. There is need to build capacity of lower health facilities to construct DR-TB regimens and manage adverse effects.

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Mapping the Pharmacogenetic Landscape in a Ugandan Population: Implications for Personalized Medicine in an Underrepresented Population

Samarasinghe,

Lee,

Corpas

et al. 2024

Clin Pharma and Therapeutics

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Africans are extremely underrepresented in global genomic research. African populations face high burdens of communicable and non‐communicable diseases and experience widespread polypharmacy. As population‐specific genetic studies are crucial to understanding unique genetic profiles and optimizing treatments to reduce medication‐related complications in this diverse population, the present study aims to characterize the pharmacogenomics profile of a rural Ugandan population. We analyzed low‐pass whole genome sequencing data from 1998 Ugandans to investigate 18 clinically actionable pharmacogenes in this population. We utilized PyPGx to identify star alleles (haplotype patterns) and compared allele frequencies across populations using the Pharmacogenomics Knowledgebase PharmGKB. Clinical interpretations of the identified alleles were conducted following established dosing guidelines. Over 99% of participants displayed actionable phenotypes across the 18 pharmacogenes, averaging 3.5 actionable genotypes per individual. Several variant alleles known to affect drug metabolism (i.e., CYP3A5*1, CYP2B6*9, CYP3A5*6, CYP2D6*17, CYP2D6*29, and TMPT*3C)—which are generally more prevalent in African individuals—were notably enriched in the Ugandan cohort, beyond reported frequencies in other African peoples. More than half of the cohort exhibited a predicted impaired drug response associated with CFTR, IFNL3, CYP2B6, and CYP2C19, and approximately 31% predicted altered CYP2D6 metabolism. Potentially impaired CYP2C9, SLCO1B1, TPMT, and DPYD metabolic phenotypes were also enriched in Ugandans compared with other African populations. Ugandans exhibit distinct allele profiles that could impact drug efficacy and safety. Our findings have important implications for pharmacogenomics in Uganda, particularly with respect to the treatment of prevalent communicable and non‐communicable diseases, and they emphasize the potential of pharmacogenomics‐guided therapies to optimize healthcare outcomes and precision medicine in Uganda.

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Treatment outcomes of drug resistant tuberculosis patients with multiple poor prognostic indicators in Uganda: A countrywide 5-year retrospective study

Cited by 28 publications

References 31 publications

Treatment outcomes of pregnant women with drug-resistant tuberculosis in Uganda: A retrospective review of 18 cases

Treatment outcomes of pregnant women with drug-resistant tuberculosis in Uganda: A retrospective review of 18 cases

Multidisciplinary management of difficult-to-treat drug resistant tuberculosis: a review of cases presented to the national consilium in Uganda

Mapping the Pharmacogenetic Landscape in a Ugandan Population: Implications for Personalized Medicine in an Underrepresented Population

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