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Item Treatment outcomes of drug resistant tuberculosis patients with multiple poor prognostic indicators in Uganda: A countrywide 5-year retrospective study(Elsevier, 2021) Baruch Baluku, Joseph; 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, WilliamBackground: Comorbid conditions and adverse drug events are associated with poor treatment outcomes among patients with drug resistant tuberculosis (DR – TB). This study aimed at determining the treatment outcomes of DR – TB patients with poor prognostic indicators in Uganda. Methods: We reviewed treatment records of DR – TB patients from 16 treatment sites in Uganda. Eligible patients had confirmed DR – TB, a treatment outcome in 2014–2019 and at least one of 15 pre-defined poor prognostic indicators at treatment initiation or during therapy. The pre-defined poor prognostic indicators were HIV co infection, diabetes, heart failure, malignancy, psychiatric illness/symptoms, severe anaemia, alcohol use, ciga rette smoking, low body mass index, elevated creatinine, hepatic dysfunction, hearing loss, resistance to fluo roquinolones and/or second-line aminoglycosides, previous exposure to second-line drugs (SLDs), and pregnancy. Tuberculosis treatment outcomes were treatment success, mortality, loss to follow up, and treatment failure as defined by the World Health Organisation. We used logistic and cox proportional hazards regression analysis to determine predictors of treatment success and mortality, respectively. Results: Of 1122 DR – TB patients, 709 (63.2%) were male and the median (interquartile range, IQR) age was 36.0 (28.0–45.0) years. A total of 925 (82.4%) had ≥2 poor prognostic indicators. Treatment success and mortality occurred among 806 (71.8%) and 207 (18.4%) patients whereas treatment loss-to-follow-up and failure were observed among 96 (8.6%) and 13 (1.2%) patients, respectively. Mild (OR: 0.57, 95% CI 0.39–0.84, p = 0.004), moderate (OR: 0.18, 95% CI 0.12–0.26, p < 0.001) and severe anaemia (OR: 0.09, 95% CI 0.05–0.17, p < 0.001) and previous exposure to SLDs (OR: 0.19, 95% CI 0.08–0.48, p < 0.001) predicted lower odds of treatment success while the number of poor prognostic indicators (HR: 1.62, 95% CI 1.30–2.01, p < 0.001), for every additional poor prognostic indicator) predicted mortality. Conclusion: Among DR – TB patients with multiple poor prognostic indicators, mortality was the most frequent unsuccessful outcomes. Every additional poor prognostic indicator increased the risk of mortality while anaemia and previous exposure to SLDs were associated with lower odds of treatment success. The management of anaemia among DR – TB patients needs to be evaluated by prospective studies. DR – TB programs should also optimise DR – TB treatment the first time it is initiated.Item Anemia in Ugandan pregnant women: a cross-sectional, systematic review and meta-analysis study(Tropical medicine and health, 2021-02-19) Bongomin, Felix; Olum, Ronald; Kyazze, Andrew Peter; Ninsiima, Sandra; Nattabi, Gloria; Nakyagaba, Lourita; Nabakka, Winnie; Kukunda, Rebecca; Ssekamatte, Phillip; Kibirige, Davis; Cose, Stephen; Nakimuli, Annettee; Baruch Baluku, Joseph; Andia-Biraro, IreneBackground: Anemia in pregnancy represents a global public health concern due to wide ranging maternal and neonatal adverse outcomes in all peripartum periods. We estimated the prevalence and factors associated with anemia in pregnancy at a national obstetrics and gynecology referral hospital in Uganda and in addition performed a systematic review and meta-analysis of the overall burden of anemia in pregnancy in Uganda. Methods: We conducted a cross-sectional study among 263 pregnant women attending the antenatal care clinic of Kawempe National Referral Hospital, Kampala, Uganda, in September 2020. Anemia in pregnancy was defined as a hemoglobin level of < 11.0 g/dl and microcytosis as a mean corpuscular volume (MCV) of < 76 fL. We also performed a systematic review (PROSPERO Registration ID: CRD42020213001) and meta-analysis of studies indexed on MEDLINE, Embase, African Journal Online, ClinicalTrials.gov, ICTRP, and the Cochrane Library of systematic review between 1 January 2000 and 31 September 2020 reporting on the prevalence of anemia in pregnancy in Uganda. Results: The prevalence of anemia was 14.1% (n= 37) (95%CI 10.4–18.8), of whom 21 (56.8%) had microcytic anemia. All cases of anemia occurred in the second or third trimester of pregnancy and none were severe. However, women with anemia had significantly lower MCV (75.1 vs. 80.2 fL, p<0.0001) and anthropometric measurements, such as weight (63.3 vs. 68.9kg; p=0.008), body mass index (25.2 vs. 27.3, p=0.013), hip (98.5 vs. 103.8 cm, p=0.002), and waist (91.1 vs. 95.1 cm, p=0.027) circumferences and mean systolic blood pressure (BP) (118 vs 125 mmHg, p=0.014). Additionally, most had BP within the normal range (59.5% vs. 34.1%, p=0.023). The comparison meta-analysis of pooled data from 17 published studies of anemia in pregnancy in Uganda, which had a total of 14,410 pregnant mothers, revealed a prevalence of 30% (95% CI 23–37). Conclusions: Despite our study having a lower prevalence compared to other studies in Uganda, these findings further confirm that anemia in pregnancy is still of public health significance and is likely to have nutritional causes, requiring targeted interventions. A larger study would be necessary to demonstrate potential use of basic clinical parameters such as weight or blood pressure as screening predictors for anemia in pregnancy.Item Cardiovascular risk factors among people with drug-resistant tuberculosis in Uganda(BMC, 2022-10-10) Baruch Baluku, Joseph; Nabwana, Martin; Nalunjogi, Joanitah; Muttamba, Winters; Mubangizi, Ivan; Nakiyingi, Lydia; Ssengooba, Willy; Olum, Ronald; Bongomin, Felix; Andia-Biraro, Irene; Worodria, WilliamBackground Tuberculosis (TB) and its risk factors are independently associated with cardiovascular disease (CVD). We determined the prevalence and associations of CVD risk factors among people with drug-resistant tuberculosis (DRTB) in Uganda. Methods In this cross-sectional study, we enrolled people with microbiologically confirmed DRTB at four treatment sites in Uganda between July to December 2021. The studied CVD risk factors were any history of cigarette smoking, diabetes mellitus (DM) hypertension, high body mass index (BMI), central obesity and dyslipidaemia. We used modified Poisson regression models with robust standard errors to determine factors independently associated with each of dyslipidaemia, hypertension, and central obesity. Results Among 212 participants, 118 (55.7%) had HIV. Overall, 196 (92.5%, 95% confidence interval (CI) 88.0-95.3) had≥1 CVD risk factor. The prevalence; 95% CI of individual CVD risk factors was: dyslipidaemia (62.5%; 55.4–69.1), hypertension (40.6%; 33.8–47.9), central obesity (39.3%; 32.9–46.1), smoking (36.3%; 30.1–43.1), high BMI (8.0%; 5.0–12.8) and DM (6.5%; 3.7–11.1). Dyslipidaemia was associated with an increase in glycated haemoglobin (adjusted prevalence ratio (aPR) 1.14, 95%CI 1.06–1.22). Hypertension was associated with rural residence (aPR 1.89, 95% CI 1.14– 3.14) and previous history of smoking (aPR 0.46, 95% CI 0.21–0.98). Central obesity was associated with increasing age (aPR 1.02, 95%CI 1.00–1.03), and elevated diastolic blood pressure (aPR 1.03 95%CI 1.00–1.06). Conclusion There is a high prevalence of CVD risk factors among people with DRTB in Uganda, of which dyslipidaemia is the commonest. We recommend integrated services for identification and management of CVD risk factors in DRTB.Item Aspergillus-specific IgM/IgG antibody serostatus of patients hospitalized with moderate-critical COVID-19 in Uganda(African Health Sciences, 2022-09-03) Bongomin, Felix; Kwizera, Richard; Mande, Emmanuel; Aloyo, Sharley Melissa; Achan, Beatrice; Namusobya, Martha; Sereke, Senai Goitom; Batte, Charles; Kiguli, Sarah; Baruch Baluku, Joseph; Joloba, Moses L; Kirenga, Bruce JInvasive pulmonary aspergillosis is known to complicate the coronavirus diseases-2019 (COVID-19), especially those with crit ical illness. We investigated the baseline anti-Aspergillus antibody serostatus of patients with moderate-critical COVID-19 hos pitalized at 3 COVID-19 Treatment Units in Uganda. All 46 tested patients, mean age 30, and 11% with underlying respiratory disease had a negative serum anti-Aspergillus IgM/IgG antibody immunochromatographic test on day 3 (mean) of symptom onset (range 1-26), but follow up specimens to assess seroconversion were not available.Item Gender diferences among patients with drug resistant tuberculosis and HIV co-infection in Uganda: a countrywide retrospective cohort study(Springer, 2021-10-18) Baruch Baluku, Joseph; Mukasa, David; Bongomin, Felix; Stadelmann, Anna; Nuwagira, Edwin; Haller, Sabine; Ntabadde, Kauthrah; Turyahabwe, StaviaBackground: Gender diferences among patients with drug resistant tuberculosis (DRTB) and HIV co-infection could afect treatment outcomes. We compared characteristics and treatment outcomes of DRTB/HIV co-infected men and women in Uganda. Methods: We conducted a retrospective chart review of patients with DRTB from 16 treatment sites in Uganda. Eligible patients were aged≥18 years, had confrmed DRTB, HIV co-infection and a treatment outcome registered between 2013 and 2019. We compared socio-demographic and clinical characteristics and tuberculosis treatment outcomes between men and women. Potential predictors of mortality were determined by cox proportional hazard regression analysis that controlled for gender. Statistical signifcance was set at p<0.05. Results: Of 666 DRTB/HIV co-infected patients, 401 (60.2%) were men. The median (IQR) age of men and women was 37.0 (13.0) and 34.0 (13.0) years respectively (p<0.001). Men were signifcantly more likely to be on tenofovir-based antiretroviral therapy (ART), high-dose isoniazid-containing DRTB regimen and to have history of cigarette or alcohol use. They were also more likely to have multi-drug resistant TB, isoniazid and streptomycin resistance and had higher creatinine, aspartate and gamma-glutamyl aminotransferase and total bilirubin levels. Conversely, women were more likely to be unemployed, unmarried, receive treatment from the national referral hospital and to have anemia, a capreomycin-containing DRTB regimen and zidovudine-based ART. Treatment success was observed among 437 (65.6%) and did not difer between the genders. However, mortality was higher among men than women (25.7% vs. 18.5%, p=0.030) and men had a shorter mean (standard error) survival time (16.8 (0.42) vs. 19.0 (0.46) months), Log Rank test (p=0.046). Predictors of mortality, after adjusting for gender, were cigarette smoking (aHR=4.87, 95% CI 1.28–18.58, p=0.020), an increase in alanine aminotransferase levels (aHR=1.05, 95% CI 1.02–1.07, p<0.001), and his tory of ART default (aHR=3.86, 95% CI 1.31–11.37, p=0.014) while a higher baseline CD4 count was associated with lower mortality (aHR=0.94, 95% CI 0.89–0.99, p=0.013 for every 10 cells/mm3 increment). Conclusion: Mortality was higher among men than women with DRTB/HIV co-infection which could be explained by several sociodemographic and clinical differences.Item Prevalence of cardiovascular risk factors in active tuberculosis inAfrica: a systematic review and meta‑analysis(Scientifc Reports, 2022-09-19) Baruch Baluku, Joseph; Olum, Ronald; Bagasha, Peace; Okello, Emmy; Bongomin, FelixPeople with tuberculosis (TB) are at risk of major adverse cardiovascular events. We estimated the prevalence of cardiovascular risk (CVR) factors among people with active TB in Africa. This was a systematic review and meta-analysis of studies from Africa. We searched EMBASE, MEDLINE through PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, mRCTs, Clinical trials.gov, and International Clinical Trials Registry Platform from inception to 31st December 2021. Among 110 eligible studies, 79 (238,316 participants) were included in the meta-analysis for smoking, 67 (52,793 participants) for current alcohol use, 30 (31,450 participants) for hazardous alcohol use, 51 (37,879 participants) for diabetes mellitus (DM), 19 (18,211 participants) for hypertension and 18 (13,910 participants) for obesity. The pooled prevalence was 26.0% (95% confidence interval 22.0–29.0) for smoking, 30.0% (25.0–35.0) for any current alcohol use, 21.0% (17.0–26.0) for hazardous alcohol use, 14.0% (9.0–18.0) for hypertension, 7.0% (6.0–9.0) for DM, and 4.0% (2.0–5.0) for obesity. Cost effective strategies are needed to screen for CVR factors among people with active TB in Africa.Item Multidisciplinary management of difcult-to-treat drug resistant tuberculosis: a review of cases presented to the national consilium in Uganda(BMC Pulmonary Medicine, 2021-06-03) Baruch Baluku, Joseph; Katuramu, Richard; Naloka, Joshua; Kizito, Enock; Nabwana, Martin; Bongomin, FelixBackground: 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 efects (24.0%) while the most frequent con silium 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. Addition ally, 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.Item COVID-19, HIV-Associated Cryptococcal Meningitis, Disseminated Tuberculosis and Acute Ischaemic Stroke: A Fatal Foursome(Dove Medical Press, 2021-10-09) Bongomin, Felix; Sereke, Senai Goitom; Okot, Jerom; Katsigazi, Ronald; Kandole, Tadeo Kiiza; Oriekot, Anthony; Olum, Ronald; Atukunda, Angella; Baruch Baluku, Joseph; Nakwagala, FrederickBackground: Several viral, bacterial and fungal co-infections have been associated with increased morbidity and mortality among patients with COVID-19. We report a fatal case of severe COVID-19 pneumonia in a patient with a recent diagnosis of advanced HIV disease complicated by cryptococcal meningitis, disseminated tuberculosis and acute ischemic stroke. Case Presentation: A 37-year-old Ugandan woman was diagnosed with HIV infection 8 days prior to her referral to our center. She was antiretroviral naïve. Her chief complaints were worsening cough, difficulty in breathing, fever and altered mental status for 3 days with a background of a 1-month history of coughing with associated drenching night sweats and weight loss. The reverse transcriptase–polymerase chain reaction for SARS-CoV-2 of her nasopharyngeal swab sample was positive. Chest radiograph demonstrated military pattern involvement of both lungs. The serum and cerebrospinal fluid cryptococcal antigen tests were positive. Urine lipoarabinomannan and sputum GeneXpert were positive for Mycobacterium tuberculosis. Computed tomography of the brain showed a large acute ischemic infarct in the territory of the right middle cerebral artery. Regardless of the initiation of treatment, that is, fluconazole 1200 mg once daily, enoxaparin 60 mg, intravenous (IV) dexamethasone 6 mg once daily, oral fluconazole 1200 mg once daily, IV piperacillin/tazobactam 4.5 g three times daily and oxygen therapy, the patient passed on within 36 hours of admission.Item Prevalence of Intestinal Helminth Coinfection in Drug-Resistant Tuberculosis in Uganda(Oxford University Press, 2022-10-08) Baruch Baluku, Joseph; Nakazibwe, Bridget; Wasswa, Amir; Naloka, Joshua; Ntambi, Samuel; Waiswa, Damalie; Okwir, Mark; Nabwana, Martin; Bongomin, Felix; Katuramu, Richard; Nuwagira, Edwin; Ntabadde, Kauthrah; Katongole, Paul; Senyimba, Catherine; Andia-Biraro, IreneBackground. Although a third of people with tuberculosis (TB) are estimated to be coinfected with helminths, the prevalence is largely unknown among people with drug-resistant TB (DR-TB). We determined the prevalence of helminth coinfection among people with DR-TB in Uganda. Methods. In a multicenter, cross-sectional study, eligible Ugandan adults with confirmed DR-TB were consecutively enrolled between July to December 2021 at 4 treatment centers. Sociodemographic data were collected using a questionnaire. Participants underwent anthropometric and blood pressure measurements, and blood samples were evaluated for random blood glucose, glycated hemoglobin, nonfasting lipid profile, human immunodeficiency virus (HIV) infection, and a complete blood count. Fresh stool samples were evaluated for adult worms, eggs, and larvae using direct microscopy after Kato-Katz concentration techniques. Results. Of 212 participants, 156 (73.6%) were male, 118 (55.7%) had HIV, and 3 (2.8%) had malaria coinfection. The prevalence of intestinal helminth coinfection was 4.7% (10/212) (95% confidence interval, 2.6%–8.6%). The frequency of helminth infections was Ancylostoma duodenale (n=4), Schistosoma mansoni (n=2), Enterobius vermicularis (n=2), Ascaris lumbricoides (n=1), and Trichuris trichiura (n=1). Conclusions. The prevalence of helminth coinfection was low among people with DR-TB. More studies are needed to determine the clinical relevance of helminth/DR-TB coinfection.Item Prevalence of anaemia and associated factors among people with pulmonary tuberculosis in Uganda(Epidemiology and Infection, 2022-01-08) Baruch Baluku, Joseph; Mayinja, Ernest; Mugabe, Pallen; Ntabadde, Kauthrah; Olum, Ronald; Bongomin, Felix