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Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis
(Journal of Fungi, 2017-05-29) Bongomin, Felix; Harris, Chris; Foden, Philip; Kosmidis, Chris; Denning, David W.
We evaluated the expression of biomarkers of innate and adaptive immune response in correlation with underlying conditions in 144 patients with chronic pulmonary aspergillosis (CPA). Patients with complete medical and radiological records, white cell counts, and a complete panel of CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were included. Eighty-four (58%) patients had lymphopenia. Six (4%) patients had lymphopenia in all five CD variables. There were 62 (43%) patients with low CD56 and 62 (43%) patients with low CD19. Ten (7%) patients had isolated CD19 lymphopenia, 18 (13%) had isolated CD56 lymphopenia, and 15 (10%) had combined CD19 and CD56 lymphopenia only. Forty-eight (33%) patients had low CD3 and 46 (32%) had low CD8 counts. Twenty-five (17%) patients had low CD4, 15 (10%) of whom had absolute CD4 counts <200/μL. Multivariable logistic regression showed associations between: low CD19 and pulmonary sarcoidosis (Odds Ratio (OR), 5.53; 95% Confidence Interval (CI), 1.43–21.33; p = 0.013), and emphysema (OR, 4.58; 95% CI; 1.36–15.38; p = 0.014), low CD56 and no bronchiectasis (OR, 0.27; 95% CI, 0.10–0.77; p = 0.014), low CD3 and both multicavitary CPA disease (OR, 2.95; 95% CI, 1.30–6.72; p = 0.010) and pulmonary sarcoidosis (OR, 4.94; 95% CI, 1.39–17.57; p = 0.014). Several subtle immune defects are found in CPA.
Prevalence and Factors Associated with Contraceptive Use among HIV-Infected Women of Reproductive Age Attending Infectious Disease Clinic at Gulu Regional Referral Hospital, Northern Uganda
(BioMed Research International, 2018-06-10) Bongomin, Felix; Chelangat, Mercy; Eriatu, Anthony; Onen, Bruno Chan; Cheputyo, Priscilla; Godmercy, Stephen A.; Ekuk, Eddymond; Idony, Francis; Obol, James Henry
Background. Reproductive planning by HIV-infected women is essential, as it helps to prevent transmission of HIV to their unborn babies. Integrating contraceptive services to routine HIV care signifcantly increases the use of modern contraceptive methods, thus reducing vertical transmission of HIV. Objectives. To determine the prevalence and factors associated with contraceptive use among HIV-infected women attending Infectious Disease Clinic (IDC) at Gulu Regional Referral Hospital (GRRH) in Northern Uganda. Methodology. A hospital-based cross-sectional study was performed. We used simple random sampling to recruit HIV-infected women receiving routine care from IDC, GRRH, into our study. Sample size was estimated using modifed Kish-Leslie formula and semistructured questionnaire was used for data collection. Data was entered into EpiData version 3.1 and analysed using Stata v11.0. We used logistic regression model to assess the associations and any factor with p≤0.05 was considered statistically signifcant. Results. Te prevalence of contraceptive use was found to be 36% (95% CI 31 – 40%). Factors which promoted contraceptive use were as follows: being married (aOR=2.68, 95% CI 1.54-4.65, p<0.001) and monthly income of $35 -250 (aOR= 2.38, 95% CI: 1.39- 4.09, p=0.002). Factors that hindered contraceptive use were having no child (nulliparity) (aOR= 0.16; 95% CI: 0.05-0.49; p=0.002) and age range of 31-49 years (aOR= 0.53; 95% CI: 0.33 - 0.84; p=0.007). Conclusion. In this study, just over a third of sexually active HIV-infected women reported use of modern contraceptives. Tis is a low level of usage and, therefore, clinicians and stakeholders should sensitise HIV-infected women on the importance of contraceptive use in the fight against HIV/AIDS and encourage them to use contraceptives to avoid vertical transmission of HIV through unintended pregnancy.
Isavuconazole and voriconazole for the treatment of chronic pulmonary aspergillosis: A retrospective comparison of rates of adverse events
(Mycoses, 2018-12-13) Bongomin, Felix; Maguire, Niamh; Moore, Caroline B.; Felton, Timothy; Rautemaa-Richardson, Riina
Background: Long-term oral triazole antifungal therapy is the cornerstone of man agement for patients with chronic pulmonary aspergillosis (CPA). Itraconazole is the first-line choice of treatment. Voriconazole, posaconazole or isavuconazole can be used as alternative treatments in case of resistance or intolerance. All of these can cause significant adverse drug reactions. Objectives: To evaluate how CPA patients tolerate voriconazole and isavuconazole after prior triazole therapy. Methods: We performed a retrospective observational study at the UK National Aspergillosis Centre. Medical records for all consecutive CPA patients started on isa vuconazole and voriconazole during an observation period of 12 and 6 months re spectively were analysed. Results: During this study period, 20 patients were started on isavuconazole and 21 patients on voriconazole. Adverse events were seen in 18 of 21 (86%) the patients in the voriconazole group and 12 of 20 (60%) in the isavuconazole group (P = 0.02). For those who developed adverse events to these agents, the rates of discontinuation of therapy were comparable (ie 10/18 [56%], voriconazole vs 8/12 [67%], isavucona zole; P = 0.54). Five (25%) patients in the isavuconazole group who were intolerant to other triazoles tolerated the standard dose of isavuconazole. Conclusions: Compared with isavuconazole, adverse events were significantly higher in CPA patients commenced on voriconazole. Isavuconazole may be an option for those patients who are intolerant to other triazoles.
Cor pulmonale complicating chronic pulmonary aspergillosis with fatal consequences: Experience from Uganda
(Medical mycology case reports, 2019-07-04) Bongomin, Felix; Kwizera, Richard; Atukunda, Angella; Kirengaa, Bruce J.
Cor pulmonale is a rare complication of pulmonary aspergillosis (CPA). A 45-year-old Ugandan male with a history of recurrent community-acquired pneumonias was admitted with symptoms of progressive difficulty in breathing, chronic productive cough, non-exertional left sided chest pain and progressive weight loss occurring over a 12-month period. Chest CT scan and echocardiography confirmed the diagnosis of CPA with an asper gilloma complicating bronchiectasis, complicated with cor pulmonale. However, this was previously clinically misdiagnosed as PTB.
Prevalence and Predictors of CD4+ T-Lymphocytopenia Among HIV-Negative Tuberculosis Patients in Uganda
(Taylor & Francis, 2020) Baruch Baluku, Joseph; Musaazi, Joseph; Mulwana, Rose; Mugabo, Araali Robert; Bongomin, Felix; Katagira, Winceslaus
Purpose: CD4+ T-lymphocytopenia is a risk for tuberculosis (TB) infection, reactivation and severe disease. We sought to determine the prevalence and predictors of CD4 T-lymphocytopenia among HIV-negative patients with bacteriologically confirmed TB in Uganda. Patients and Methods: Eligible participants were adult HIV-negative patients with bacter iologically confirmed TB at the National TB Treatment Centre in Uganda. CD4+ and CD8+ T-lymphocyte counts were determined by flow cytometry. We defined CD4+ T-lymphocytopenia as a CD4+ T-lymphocyte count of <418 cells/mm3 as per the population estimate for Ugandans. We performed logistic regression analysis to determine predictors of CD4+ T-lymphocytopenia. Results: We enrolled 216 participants whose mean age (standard deviation (±SD)) was 32.5 (±12.1) years, of whom 146 (67.6%) were males. The prevalence of CD4+ T-lymphocytopenia was 25% (54/216) (95% confidence interval (CI): 19.6–31.2%). Patients with anaemia (adjusted odds ratio (aOR): 3.83, 95% CI: 1.59–9.23, p = 0.003), weight loss (aOR: 3.61, 95% CI: 1.07–12.23, p = 0.039) and a low CD8+ T-cell count (aOR: 6.10, 95% CI: 2.68–13.89, p < 0.001) were more likely to have CD4+ T-lymphocytopenia while those with monocytosis (aOR: 0.35, 95% CI: 0.14–0.89, p = 0.028) were less likely to have CD4+ T-lymphocytopenia. Conclusion: There was a high prevalence of CD4+ T-lymphocytopenia among HIV negative TB patients. Patients with weight loss, anaemia and a low CD8+ count were more likely to have CD4+ T-lymphocytopenia while those with monocytosis were less likely to have CD4+ lymphocytopenia. The findings suggest that CD4+ lymphocytopenia is indicative of severe disease and globally impaired cell-mediated immune responses against TB
Impact of high baseline Aspergillus-specific IgG levels on weight and quality-of-life outcomes of patients with chronic pulmonary aspergillosis
(Medical Mycology, 2020-04-02) Bongomin, Felix; Garcez, Tomaz; Denning, David W.
This study aimed to evaluate the impact of quantitative baseline Aspergillus-specific immunoglobulin G (IgG) serum levels on weight changes of patients with chronic pulmonary aspergillosis (CPA) under antifungal treatment. We retrospectively reviewed data of patients diagnosed with CPA between April 2015 and March 2018 at the National Aspergillosis Centre (Manchester, UK). All patients were on continued antifungal treat ment for 12 months. Data on Aspergillus-specific IgG levels, St George’s quality of life (SGQoL) variables and weight at baseline, 6 months and 12 months were extracted. We defined a high serum Aspergillus-specific IgG as ≥ 200 mg/l (Group A) and low level < 200 mg/l (Group B). Forty-nine patients (37 male; 12 female), median age 65 years (range: 29–86) were studied. Overall, 33% (n = 16) of the patients were in Group A. The baseline characteristics between the two groups were similar. The median Charlson comorbidity index was 4 (range: 0–5) and 3 (range: 0–9) for Group A and Group B, respectively (P = .543). There was a sustained decline in median Aspergillus IgG levels from baseline, through 6 month to 12 months of continues therapy from 170 (range: 20–1110) to 121 (range: 20–1126), and finally 107 (15–937) mg/l, respectively (P < .001). Group A patients gained more weight at 6 months (9/15 [60%] vs. 7/33 [21%], P = .012) and at 12 months of treatment (9/15 [60%] vs. 7/33 [22%]), and more patients in Group B lost weight ((13/33 [41%] vs. 1/15 [7%]), P = .015). However, there was no difference in QoL outcomes across groups at 6 (P = .3) and 12 (P = .7) months. A very high Aspergillus IgG may confer a higher likelihood of weight gain as a key, objective marker of clinical response, if patients can tolerate 12 months of antifungal therapy.
Absolute eosinophil count correlates with temperature and CD4 count independently of HIV infection among tuberculosis patients
(Tropical Medicine and International Health, 2020-09) Baruch Baluku, Joseph; Tukumbo Anguzu, Godwin; Bongomin, Felix; Mirembe Byonanebye, Dathan
objective To determine clinical correlates of the peripheral absolute eosinophil count (AEC) among bacteriologically confirmed TB patients in Uganda. materials and methods We evaluated data of bacteriologically confirmed adult TB patients who had a peripheral blood AEC measurement at the National TB Treatment Center in Uganda during a cross-sectional study. We performed linear regression analysis for correlates of log-transformed AEC. results We included 235 patients in this analysis with a median (interquartile range, IQR) age of 31 (24–39) years. 60.4% were male, and 33.6% had TB/HIV co-infection. In a multivariable linear regression model that controlled for age, residence type, HIV status, weight loss, anorexia, body mass index, CD8+ T-cell count, haemoglobin level and TB bacillary load, males had a 47.0% higher AEC than females (adjusted coefficient (R2 ) = 0.385, 95% confidence interval (CI) 0.012–0.759 P = 0.043). Also, a 1 °C raise in temperature resulted in an 11.5% decrease in the AEC (R2 = 0.122 95% CI ( 0.233 to 0.011) P = 0.031) while a 1 cell/mm3 increase in the CD4+ T cell count resulted in a 0.10% increase in the AEC (R2 = 0.001 95% CI (0.000–0.001) P = 0.032). conclusion The AEC was higher among males than females, consistent with the normal population distribution of AEC among Ugandans. The AEC was weakly but positively correlated with the CD4 count and negatively correlated with temperature.
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, William
Background: 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.
COVID-19 vaccine acceptance among high-risk populations in Uganda
(Therapeutic Advances in Infectious Disease, 2021) Bongomin, Felix; Olum, Ronald; Andia-Biraro, Irene; Nakwagala, Frederick Nelson; Hudow Hassan, Khalid; Nassozi, Dianah Rhoda; Kaddumukasa, Mark; Byakika-Kibwika, Pauline; Kiguli, Sarah; Kirenga, Bruce J.
Background: Immunization is an important strategy for controlling the COVID-19 pandemic. COVID-19 vaccination was recently launched in Uganda, with prioritization to healthcare workers and high-risk individuals. In this study, we aimed to determine the acceptability of COVID-19 vaccine among persons at high risk of COVID-19 morbidity and mortality in Uganda. Methods: Between 29 March and 14 April 2021, we conducted a cross-sectional survey consecutively recruiting persons at high risk of severe COVID-19 (diabetes mellitus, HIV and cardiovascular disease) attending Kiruddu National Referral Hospital outpatient clinics. A trained research nurse administered a semi-structured questionnaire assessing demographics, COVID-19 vaccine related attitudes and acceptability. Descriptive statistics, bivariate and multivariable analyses were performed using STATA 16. Results: A total of 317 participants with a mean age 51.5±14.1years were recruited. Of this, 184 (60.5%) were female. Overall, 216 (70.1%) participants were willing to accept the COVID-19 vaccine. The odds of willingness to accept COVID-19 vaccination were four times greater if a participant was male compared with if a participant was female [adjusted odds ratio (AOR): 4.1, 95% confidence interval (CI): 1.8–9.4, p=0.00]. Participants who agreed (AOR: 0.04, 95% CI: 0.01–0.38, p=0.003) or strongly agreed (AOR: 0.04, 95% CI: 0.01–0.59, p=0.005) that they have some immunity against COVID-19 were also significantly less likely to accept the vaccine. Participants who had a history of vaccination hesitancy for their children were also significantly less likely to accept the COVID-19 vaccine (AOR: 0.1, 95% CI: 0.01–0.58, p=0.016). Conclusion: The willingness to receive a COVID-19 vaccine in this group of high-risk individuals was comparable to the global COVID-19 vaccine acceptance rate. Increased sensitization, myth busting and utilization of opinion leaders to encourage vaccine acceptability is recommended.
Internal Medicine Clerkship Amidst COVID-19 Pandemic: A Cross-Sectional Study of the Clinical Learning Experience of Undergraduate Medical Students at Makerere University, Uganda
(Dove Press, 2021) Bongomin, Felix; Olum, Ronald; Nakiyingi, Lydia; Lalitha, Rejani; Ssinabulya, Isaac; Sekaggya Wiltshire, Christine; Ocama, Ponsiano; Byakika-Kibwika, Pauline
Background: The coronavirus-2019 (COVID-19) pandemic continues to impose a significant impact on medical education. We aimed to describe the clinical learning experience of undergraduate medical students undertaking internal medicine clerkship during the COVID-19 pandemic at Makerere University, Uganda. Methods: A descriptive, cross-sectional study among medical students in clinical years of study pursuing the Bachelor of Medicine and Bachelor of Surgery undergraduate degree program was conducted in November 2020. Only 3rd (junior clerks) and 5th (senior clerks) year medical students whose internal medicine clerkships were interrupted by the COVID-19 pandemic were studied. Results: Data of 188 (95%) eligible clinical year students; junior (101, 54.0%) and senior (86, 46.0%) were analysed. Median age was 24 (range: 22–42) years. Majority (70.1%) were male and Ugandan nationals (94.1%). Sixty-four (30.3%) students reported inadequate personal protective equipment, 152 (81.7%) felt at risk of contracting COVID-19, and 127 (67.9%) said it was difficult to observe COVID-19 standard operating procedures. Twenty two students (11.9%) were discouraged from pursuing a career in internal medicine. Overall, most students reported good or excellent clinical experience pre-COVID-19 era compared to during the COVID-19 era (4.0 vs 3.5, p<0.0001). Senior clerks significantly believed that the time allocated for the rotation was adequate (p<0.0001) and they were able to complete their study objectives (p<0.001), compared to the junior clerks. Senior clerks believed that learning was difficult when combined with junior clerks (p=0.013). About half of the students (51.4%, n=95) reported clinical teaching should remain as it was in the pre COVID-19 era. Conclusion: The COVID-19 pandemic has had a significantly negative effect on the clinical learning experience of the students. There is need to review the current teaching and learning methods to suit teaching and learning during pandemics of highly infectious diseases to ensure safe and effective learning experience.
Predictors of laboratory spontaneous tumour lysis syndrome in children with high-grade tumours in Uganda
(Sage, 2021) Apiyo, Mirriam; Bongomin, Felix; Balagadde, Joyce; Mupere, Ezekiel; Ndeezi, Grace
High-grade malignancy is endemic in sub-Saharan Africa and is prone to the spontaneous tumour lysis syndrome. However, data on spontaneous tumour lysis syndrome remain scanty in our setting. We sought to determine the prevalence and factors associated with laboratory spontaneous tumour lysis syndrome in children in Uganda. We conducted a cross-sectional study among children <18 years old with histologically confirmed high-grade malignancy between October 2013 and April 2014. Laboratory spontaneous tumour lysis syndrome was defined as the presence of 2 of each of hyperkalaemia, hypocalcaemia, hyperuricaemia and hyperphosphatemia prior to administration of chemo therapy when alternative diagnoses had been excluded. A p < 0.05 was considered statistically significant. Of 108 chil dren, of median age 7.7 years, where boys outnumbered girls 2:1, high-grade, malignancy included Burkitt’s lymphoma, acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, acute myeloid leukaemia and Burkitt’s leukaemia, with 14 suffering with laboratory spontaneous tumour lysis syndrome. Hypocalcaemia was its most common electrolyte imbal ance; and four children died prior to commencement of chemotherapy. Bulky disease, lactate dehydrogenase levels 500 iu/l and serum creatinine levels >1.2 mg/dl were associated with laboratory spontaneous tumour lysis syndrome. However, only bulky disease was significantly predictive of laboratory spontaneous tumour lysis syndrome. Such children would benefit from routine screening
Predictors of laboratory spontaneous tumour lysis syndrome in children with high-grade tumours in Uganda
(Sage, 2021) Apiyo, Mirriam; Bongomin, Felix; Balagadde, Joyce; Mupere, Ezekiel; Ndeezi, Grace
High-grade malignancy is endemic in sub-Saharan Africa and is prone to the spontaneous tumour lysis syndrome. However, data on spontaneous tumour lysis syndrome remain scanty in our setting. We sought to determine the prevalence and factors associated with laboratory spontaneous tumour lysis syndrome in children in Uganda. We conducted a cross-sectional study among children <18 years old with histologically confirmed high-grade malignancy between October 2013 and April 2014. Laboratory spontaneous tumour lysis syndrome was defined as the presence of 2 of each of hyperkalaemia, hypocalcaemia, hyperuricaemia and hyperphosphatemia prior to administration of chemo therapy when alternative diagnoses had been excluded. A p < 0.05 was considered statistically significant. Of 108 chil dren, of median age 7.7 years, where boys outnumbered girls 2:1, high-grade, malignancy included Burkitt’s lymphoma, acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, acute myeloid leukaemia and Burkitt’s leukaemia, with 14 suffering with laboratory spontaneous tumour lysis syndrome. Hypocalcaemia was its most common electrolyte imbal ance; and four children died prior to commencement of chemotherapy. Bulky disease, lactate dehydrogenase levels 500 iu/l and serum creatinine levels >1.2 mg/dl were associated with laboratory spontaneous tumour lysis syndrome. However, only bulky disease was significantly predictive of laboratory spontaneous tumour lysis syndrome. Such children would benefit from routine screening.
Treatment outcomes of pregnant women with drug-resistant tuberculosis in Uganda: A retrospective review of 18 cases
(Elsevier, 2021-02-06) Baruch Baluku, Joseph; Bongomin, Felix
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.
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, Irene
Background: 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.
Pulmonary TB and chronic pulmonary aspergillosis: clinical differences and similarities
(International Union Against Tuberculosis and Lung Disease, 2021-02-23) Baluku, J. B.; Nuwagira, E.; Bongomin, F.; Denning, D. W.
BACKGROUND: Pulmonary TB (PTB) and chronic pulmonary aspergillosis (CPA) are both progressive and debilitating parenchymal lung diseases with overlapping risk factors, symptomatology and radiological findings that often result in misdiagnosis of either disease. METHODS: We undertook a narrative review approach to describe the clinical and radiological manifestations of CPA and PTB and highlight the salient features that differentiate these two closely related maladies. RESULTS: CPA is a frequent complication of treated PTB. In fact, 15–90% of CPA cases occur in patients with residual lung lesions following treatment for PTB. While CPA predominantly affects older patients with underlying lung diseases, both PTB and CPA present with clinically indistinguishable symptoms. Chest imaging findings of cavitation and fibrosis are common to both diseases. However, lymphadenopathy, miliary pattern and pleural effusion are predictive of active PTB, while aspergilloma, pleural thickening and para cavitary fibrosis are more common in CPA. Aspergillus specific IgG serology has a central role in differentiating PTB (both active and healed) from CPA with a high sensitivity and specificity. CONCLUSION: Aspergillus-specific IgG serology is key in differentiating PTB and PTB relapse from CPA. It may be worthwhile developing clinical predictive scores that can be used in low-income settings to differentiate active TB, post-TB disease and TB+CPA co-infection
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, Felix
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 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.
Utility of St. George’s respiratory questionnaire in predicting clinical recurrence in chronic pulmonary aspergillosis
(Therapeutic Advances in Infectious Disease, 2021-07-06) Bongomin, Felix; Otu, Akaninyene
Background and Aims: Patients with chronic pulmonary aspergillosis (CPA) who discontinue antifungal therapy commonly exhibit disease recurrence. We aimed to evaluate the utility of the St. George’s respiratory questionnaire (SGRQ) in predicting the likelihood of clinical recurrence of CPA in patients who come off antifungal therapy. Methods: This audit included CPA patients for whom antifungal therapy was discontinued for at least 1month. Comparisons were made between the quality of life scores at the time of discontinuation of treatment and at the time of diagnosis of clinical recurrence. The change in patients’ self-assessment scores was also compared. Results: There were 33 cases and 44 controls. Of the 33 cases, 22 (67%) were males with a mean age of 62±13years. The median for the symptom component of quality of life (QoL) changed from 78.4 at the time of discontinuation of therapy to 83.1 units at the time of diagnosis of clinical failure (p=0.043), whereas that of the impact and activity components changed from 62.7 to 59.1 units (p=0.387) and 85.0 to 85.9 units (p=0.153), respectively. At 12months, the symptoms domain of SGRQ was able to discriminate between cases of clinical recurrence and controls [area under the curve (AUC) 0.7, 95% confidence interval (CI): 0.6–0.8, p=0.009]. The proportion of patients in very poor health status increased from 3/11 (9.1%) to 11/33 (33.3%) (p=0.046). Conclusion: A deteriorating symptoms component of the SGRQ and a worsening of patients’ self-assessment are associated with clinical recurrence. Failure to improve by >8 units in the symptoms domain appear to be a marker of disease recurrence. We propose that the clinical approach to diagnose recurrent CPA would be a combination of clinical history, SGRQ scoring, chest imaging and a workup to exclude other causes of the patients’ symptoms
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, Frederick
Background: 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.
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, Stavia
Background: 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.
High Mortality During the Second Wave of the Coronavirus Disease 2019 (COVID-19) Pandemic in Uganda: Experience From a National Referral COVID-19 Treatment Unit
(Oxford University Press, 2021-10-18) Bongomin, Felix; Fleischer, Brian; Olum, Ronald; Natukunda, Barbra; Kiguli, Sarah; Byakika-Kibwika, Pauline; Baruch Baluku, Joseph; Nakwagala, Frederick Nelson
Background. We evaluated clinical outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) in the second wave of the pandemic in a national COVID-19 treatment unit (CTU) in Uganda. Methods. We conducted a retrospective cohort study of COVID-19 patients hospitalized at the Mulago National Referral Hospital CTU between May 1 and July 11, 2021. We performed Kaplan-Meier analysis to evaluate all-cause in-hospital mortality. Results. Of the 477 participants, 247 (52%) were female, 15 (3%) had received at least 1 dose of the COVID-19 vaccine, and 223 (46%) had at least 1 comorbidity. The median age was 52 (interquartile range, 41–65) years. More than 80% of the patients presented with severe (19%, n = 91) or critical (66%, n = 315) COVID-19 illness. Overall, 174 (37%) patients died. Predictors of all-cause in-hospital mortality were as follows; age ≥50 years (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.2–3.2; P = .011), oxygen saturation at admission of ≥92% (aOR, 0.97; 95% CI, 0.91–0.95; P < .001), and admission pulse rate of ≥100 beats per minute (aOR, 1.01; 95% CI, 1.00–1.02; P = .042). The risk of death was 1.4-fold higher in female participants compared with their male coun terparts (hazards ratio, 1.4; 95% CI, 1.0–2.0; P = .025). Conclusions. In this cohort, where the majority of the patients presented with severe or critical illness, more than one third of the patients hospitalized with COVID-19 at a national CTU died of the illness.

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