Long COVID in Uganda: Electrographic findings among patients at risk.

Background: COVID-19 has a significant cardiovascular involvement. Electrocardiographic (ECG) abnormalities among people at a risk of Long COVID in Uganda was investigated. Methods: A cross-sectional study was conducted from February to June 2022 at the post COVID - 19 clinic in Mulago National Specialized Hospital, Kampala. A standard resting ECG was performed on individuals at least 2 months following acute COVID-19, with a negative SARS-CoV-2 reverse-transcription polymerase chain reaction. Sociodemographic and clinical characteristics as well as vital signs were recorded for all study participants. Results: Of the 244 study participants, 117 (47.9%) were female. The median age of all the participants was 33.0 (interquartile range: 26.0 - 43.5) years. Twenty-five (10.2%) participants had a history of smoking while 117 (48%) had a history of alcohol intake. In total, 46 (18.9%) had abnormal ECG findings (95% Confidence Interval (CI): 14.39 - 24.29) and non-specific T-wave inversion (n = 16, 34%) was the most frequent ECG abnormality. The proportion of participants with ECG abnormalities was 48% lower among females (adjusted prevalence ratio (aPR): 0.52, 95% CI: 0.28 - 0.96, p value < 0.05) and 2-fold greater for those with a history of smoking (aPR: 2.03, 95% CI:1.096 - 3.776, p value < 0.05). Conclusion: One in five Ugandans who were checked at the clinic at a risk of Long COVID showed ECG abnormalities. ECG screening is suggested to be integrated into the follow-up care of those at a risk of Long COVID.

Serum E-selectin and endothelial cell-specific Molecule-1 levels among people living with HIV on long term ART in Uganda: a pilot cross-sectional study.

BACKGROUND: Prolonged exposure to HIV and anti-retroviral therapy (ART) has been linked with endothelial cell activation which subsequently predisposes people living with HIV (PLWH) to cardiovascular diseases. Serum biomarkers of endothelial cell activation such as E-Selectin and endothelial cell-specific molecule-1 (ESM-1) could aid in early detection of PLWH at a risk of cardiovascular diseases. However, there is a paucity of data on these biomarkers like E-selectin and endothelial cell-specific molecule-1 (ESM-1) among PLWH on long term ART (≥ 10 years) in Uganda. The aim of this study is to determine the serum levels of these biomarkers in this population. METHODS: This was a cross-sectional study where we randomly sampled 73 stored serum samples of PLWH who were enrolled in the Infectious Diseases Institute (IDI) ART long term (ALT cohort). We measured serum levels of E-selectin and ESM-1 by ELISA. Data was summarized using median and interquartile range. Inferential statistics were performed to determine predictors of elevated levels of E-selectin. RESULTS: Of the 73 samples analyzed, 38 (52.1%) were from female participants. The mean age was 54 ± 9.0 years. Twenty participants (27.4%) had a history of smoking while 52 (71.2%) had a history of alcohol intake. Twenty-five (34.3%) of the participants were overweight whereas 4 (5.6%) were obese. Fifty-four (74%) had an undetectable viral load (≤ 0 copies/ml) and the mean duration of ART at the time of sampling (2014/2015) was 10.4 ± 0.4 years. While serum levels of ESM-1 were not detectable in any of our samples, the median E-selectin levels was 147.6 µm/L ranging from 8.44 µm/L and 1,979.36 µm/L. Sixty-seven participants (91.8%) had elevated levels of E-selectin (> 39 µm/L). CD4 count > 500 cells/µl compared to lower counts was a predictor of elevated levels of E-Selectin (adjusted Odd Ratio 12.5, 95% CI (1.03 - 149.95, p < 0.05). CONCLUSIONS: The majority (91.8%) of PLWH on long term ART had elevated levels of E-selectin. Having high CD4 count (> 500 cells/µl) was predictive of elevated levels of E-Selectin. Future work should longitudinally assess the trend of levels of E-selectin and ESM-1 while assessing for cardiovascular diseases endpoint.

The role of conventional echocardiographic parameters on detecting subclinical anthracycline therapy related cardiac dysfunction-The SATRACD study.

Background: Subclinical anthracycline therapy related cardiac dysfunction (ATRCD) can be detected with speckle tracking echocardiographic image (STE), which is not widely available in Uganda. We aimed to investigate the role of the two conventional echocardiographic parameters [mitral annular plane systolic excursion (MAPSE) and mitral annular peak systolic tissue Doppler velocity (S')] on diagnosing subclinical ATRCD. Method and results: 207 cancer patients who underwent anthracycline based chemotherapy were recruited at baseline and followed up until 6 months after ending anthracycline therapy. Comprehensive echocardiographic data were collected at each visit. Global longitudinal strain (GLS) by STE was used as the gold standard diagnostic test to define the case of subclinical ATRCD. Data of the 200 patients who had no evidence of clinical ATRCD were analyzed. One hundred and seventy-two (86.0%) were female, with a median age of 42 years and 47 (23.5%) patients were diagnosed with subclinical ATRCD at the end of anthracycline therapy by GLS criteria. The area under the curve (AUC), cutoff point, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of reduction of MAPSE (ΔMAPSE) were 0.6736 (95% CI: 0.5885, 0.7587), ≥ 2 mm, 74.5% (95% CI: 59.7%, 86.1%), 54.9% (95% CI: 46.7%, 63.0%), 33.7% (95% CI: 24.7%, 43.6%), and 87.5% (95% CI: 79.2%, 93.4%). The AUC, cutoff point, sensitivity, specificity, PPV, and NPV of reduction of S' (ΔS') were 0.6018 (95% CI: 0.5084, 0.6953), ≥ 0.5 cm/s, 61.7% (95% CI: 46.4%, 75.5%), 52.7% (95% CI: 44.4%, 60.9%), 29.0% (95% CI: 20.4%, 38.9%), and 76.1% (95% CI: 72.4%, 88.6%). When ΔMAPSE and ΔS' are used as parallel test, the net sensitivity and specificity is 89.4% and 28.8%, respectively, the net PPV and NPV is 27.8% and 90.0%, respectively. Conclusion: The ΔMAPSE and ΔS' showed fairly good accuracy, sensitivity and NPV to detect subclinical ATRCD in Ugandan cancer patients. These conventional echocardiographic parameters may serve as screening tools for detecting subclinical ATRCD in resource limited settings.

Detecting subclinical anthracycline therapy-related cardiac dysfunction in patients attending Uganda Cancer Institute.

Aims: To investigate the incidence of anthracycline therapy-related cardiac dysfunction (ATRCD) and its predictors among Ugandan cancer patients. Patients & methods: The study recruited 207 cancer patients who were followed for 6 months after ending anthracycline therapy. Global longitudinal strain and troponin-I were the diagnostic tools. Results & conclusions: The cumulative incidences of subclinical and clinical ATRCD were 35.0 and 8.8% respectively. The predictors of clinical ATRCD were HIV infection (hazard ratio [HR]: 3.04; 95% CI: 1.26-7.32; p = 0.013), lower baseline global longitudinal strain (HR: 0.61; 95% CI: 0.53-0.71; p < 0.001) and development of subclinical ATRCD at the end of anthracycline therapy (HR: 6.61; 95% CI: 2.60-16.82; p < 0.001). Cardiac surveillance at baseline and at ending of anthracycline therapy is essential to identify high-risk patients.

Anthracyclines are drugs for treating many types of cancers. They may however be harmful to the heart. This anthracycline side effect will first cause subtle heart­cell injury that can be detected and treated if it is handled early. Therefore, this study aims to study patients in the Uganda Cancer Institute to find out how many patients can get and who are likely to get this side effect. We found that 35% of the patients had subtle heart­cell injury and 8.8% had a more severe form of heart­cell injury. The patients who lived with HIV, whose heart was weaker and who got subtle heart­cell injury immediately after treatment were more likely to get the severe form of the side effect. Patients who receive anthracycline therapy need to be monitored closely to prevent serious heart injury.

Prioritizing Health-Sector Interventions for Noncommunicable Diseases and Injuries in Low- and Lower-Middle Income Countries: National NCDI Poverty Commissions.

Health sector priorities and interventions to prevent and manage noncommunicable diseases and injuries (NCDIs) in low- and lower-middle-income countries (LLMICs) have primarily adopted elements of the World Health Organization Global Action Plan for NCDs 2013-2020. However, there have been limited efforts in LLMICs to prioritize among conditions and health-sector interventions for NCDIs based on local epidemiology and contextually relevant risk factors or that incorporate the equitable distribution of health outcomes. The Lancet Commission on Reframing Noncommunicable Diseases and Injuries for the Poorest Billion supported national NCDI Poverty Commissions to define local NCDI epidemiology, determine an expanded set of priority NCDI conditions, and recommend cost-effective, equitable health-sector interventions. Fifteen national commissions and 1 state-level commission were established from 2016-2019. Six commissions completed the prioritization exercise and selected an average of 25 NCDI conditions; 15 conditions were selected by all commissions, including asthma, breast cancer, cervical cancer, diabetes mellitus type 1 and 2, epilepsy, hypertensive heart disease, intracerebral hemorrhage, ischemic heart disease, ischemic stroke, major depressive disorder, motor vehicle road injuries, rheumatic heart disease, sickle cell disorders, and subarachnoid hemorrhage. The commissions prioritized an average of 35 health-sector interventions based on cost-effectiveness, financial risk protection, and equity-enhancing rankings. The prioritized interventions were estimated to cost an additional US$4.70-US$13.70 per capita or approximately 9.7%-35.6% of current total health expenditure (0.6%-4.0% of current gross domestic product). Semistructured surveys and qualitative interviews of commission representatives demonstrated positive outcomes in several thematic areas, including understanding NCDIs of poverty, informing national planning and implementation of NCDI health-sector interventions, and improving governance and coordination for NCDIs. Overall, national NCDI Poverty Commissions provided a platform for evidence-based, locally driven determination of priorities within NCDIs.

Internal Medicine Clerkship Amidst COVID-19 Pandemic: A Cross-Sectional Study of the Clinical Learning Experience of Undergraduate Medical Students at Makerere University, Uganda.

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.

Cardiovascular risk factor mapping and distribution among adults in Mukono and Buikwe districts in Uganda: small area analysis.

BACKGROUND: Sub-Saharan Africa (SSA) is experiencing an increasing burden of Cardiovascular Diseases (CVDs). Modifiable risk factors including hypertension, diabetes, obesity, central obesity, sedentary behaviours, smoking, poor diet (characterised by inadequate vegetable and fruit consumption), and psychosocial stress are attributable to the growing burden of CVDs. Small geographical area mapping and analysis of these risk factors for CVD is lacking in most of sub-Saharan Africa and yet such data has the potential to inform monitoring and exploration of patterns of morbidity, health-care use, and mortality, as well as the epidemiology of risk factors. In the current study, we map and describe the distribution of the CVD risk factors in 20 parishes in two neighbouring districts in Uganda. METHODS: A baseline survey benchmarking a type-2 hybrid stepped wedge cluster randomised trial design was conducted in December 2018 and January 2019. A sample of 4372 adults aged 25-70 years was drawn from 3689 randomly selected households across 80 villages in 20 parishes in Mukono and Buikwe districts in Uganda. Descriptive statistics and generalized linear modelling controlled for clustering were conducted for this analysis in Stata 13.0, and a visual map showing risk factor distribution developed in QGIS. RESULTS: Mapping the prevalence of selected CVD risk factors indicated substantial gender and small area geographic heterogeneity which was masked on aggregate analysis. Patterns and clustering were observed for hypertension, physical inactivity, smoking, alcohol consumption and risk factor combination. Prevalence of unhealthy diet was very high across all parishes with no significant observable differences across areas. CONCLUSION: Modifiable cardiovascular risk factors are common in this low-income context. Moreover, across small area geographic setting, it appears significant differences in distribution of risk factors exist. These differences suggest that underlying drivers such as sociocultural, environmental and economic determinants may be promoting or inhibiting the observed risk factor prevalences which should be further explored. In addition, the differences emphasize the value of small geographical area mapping and analysis to inform more targeted risk reduction interventions.

Utility of albumin to creatinine ratio in screening for microalbuminuria among newly diagnosed diabetic patients in Uganda: a cross sectional study.

BACKGROUND: The aim of this study was to determine the prevalence and factors associated with microalbuminuria among newly diagnosed diabetic patients in Mulago National Referral Hospital, Uganda. METHODS: In this cross-sectional study conducted between June 2014 and January 2015, we collected information on patients' socio-demographics, biophysical profile, blood pressure, biochemical testing and echocardiographic findings using a pre-tested questionnaire. Bivariate and multivariate logistic regression analyses were used to investigate the association of several factors with microalbuminuria. RESULTS: Of the 175 patients recruited, males were 90(51.4%) and the mean age was 46±15 years. Majority of patients had type 2 DM 140 (80.0%) and the rest had type 1 DM 35 (20.0%). Mean glycated hemoglobin (HbA1C) was 13.9±5.3%. Mean duration of diabetes was 2 months. Prevalence of microalbuminuria was 47.4 % (95% CI: 40.0%-54.9%) overall. Pregnancy was associated with microalbuminuria (OR7.74[95%CI.1.01-76.47] P=0.050) while mild and moderate physical activity at work were inversely associated with microalbuminuria respectively (OR0.08[95%CI0.01-0.95] P=0.046) and (OR0.07[95%CI0.01-0.77] P=0.030). CONCLUSION: Prevalence of microalbuminuria was high in this group. Physical activity at work may be protective against microalbuminuria and this calls for longitudinal studies. Early detection and management of microalbuminuria in diabetics may slow progression to overt diabetic nephropathy (DN).

Integrated Hypertension and HIV Care Cascades in an HIV Treatment Program in Eastern Uganda: A Retrospective Cohort Study.

BACKGROUND: Persons living with HIV (PLHIV) are at increased risk of cardiovascular disease. Integration of services for hypertension (HTN), the primary cardiovascular disease risk factor, into HIV care programs is recommended in Uganda, though, uptake has been limited. We sought to compare the care cascades for HTN and HIV within an HIV program in Eastern Uganda. METHODS: We conducted a retrospective cohort study of all PLHIV enrolled in 3 HIV clinics between 2014 and 2017. We determined the proportion of patients in the following cascade steps over 12 months: Screened, Diagnosed, Initiated on treatment, Retained, Monitored, and Controlled. Cascades were analyzed using descriptive statistics and compared using χ and t tests. RESULTS: Of 1649 enrolled patients, 98.5% were initiated on HIV treatment, of whom 70.7% were retained in care, 100% had viral load monitoring, and 90.3% achieved control (viral suppression). Four hundred fifty-six (27.7%) participants were screened for HTN, of whom 46.9% were diagnosed, 88.1% were initiated on treatment, 57.3% were retained in care, 82.7% were monitored, and 24.3% achieved blood pressure control. There were no differences in any HIV cascade step between participants with HIV alone and those with both conditions. CONCLUSIONS: The HIV care cascade approached global targets, whereas the parallel HTN care cascade demonstrated notable quality gaps. Management of HTN within this cohort did not negatively impact HIV care. Our findings suggest that models of integration should focus on screening PLHIV for HTN and retention and control of those diagnosed to fully leverage the successes of HIV programs.

Community study to uncover the full spectrum of rheumatic heart disease in Uganda.

OBJECTIVE: Estimates of the prevalence of rheumatic heart disease (RHD) in many endemic countries are limited to samples of children attending schools, which generate an incomplete picture of disease burden in communities. The present study conducted household-based RHD screening in a representative community in Gulu district, Uganda. METHODS: Members of households identified through a two-stage cluster-sampling approach between the ages of 5 years and 50 years were invited to undergo limited cardiac testing with a handheld echocardiogram to assess for the presence of RHD. Suspicious cases underwent confirmatory echocardiogram with a fully functional machine. RESULTS: Of the 2453 community members screened, 2.45% (95% CI 1.87% to 3.14%) showed echocardiographic evidence of RHD with 1.26% (95% CI 0.860% to 1.79%) having definite RHD. The overall prevalence of RHD among participants <20 years was 2.52% (95% CI 1.78% to 3.45%), with a borderline prevalence of 1.97% (95% CI 1.33% to 2.82%) and a definite prevalence of 0.544% (95% CI 0.235% to 1.07%). Prevalence rates among youth increased with age and peaked in the age group of 16-20 years. The overall adult prevalence (>20 years) of RHD was 2.34% (95% CI 1.49% to 3.49%). The majority of definite cases were mild (81%) and marked by mitral regurgitation and associated morphological valve changes (71%). CONCLUSION: Our data reveal a high prevalence of undiagnosed RHD within an endemic community and fill a critical gap in RHD epidemiology in African adults.

Prevalence and characteristics of primary left-sided valve disease in a cohort of 15,000 patients undergoing echocardiography studies in a tertiary hospital in Uganda.

BACKGROUND: Although rheumatic heart disease remains the leading cause of valve heart disease (VHD) in developing countries, other forms of valve disease have been over shadowed and not regarded as a public health problem. However, several facts suggest that the role of non-rheumatic VHD as a significant cardiovascular disease should be reconsidered. We aimed to assess the prevalence and characteristics of different forms of primary left sided valve diseases from a series of 15,009 echocardiographic studies. METHODS: This was a retrospective review of echocardiographic reports for studies performed between January 2012 and December 2013 (24 months) at Uganda Heart Institute. All patients with primary left-sided valve disease were classified into one of five major diagnostic categories and in each diagnostic category; patients were sub-classified into stages A-D of primary valve disease as defined by the American College of Cardiology. RESULTS: Three thousand five hundred eighty-two echocardiography reports qualified for final data analysis. The "sclerotic valve changes with normal valve function", a Stage A sub-class of "degenerative valve disease" overwhelmingly overshadowed all the other diagnostic categories in this stage. "Rheumatic Heart Disease", "Degenerative Valve Disease", "Bicuspid Aortic Valve", "Mitral Valve Prolapse" and "Endomyocardial Fibrosis" diagnostic categories accounted for 53.0%, 41.8%, 2.2%, 1.4% and 1.7% respectively in stages B-D of primary VHD. Rheumatic heart disease disproportionately affected the young, productive age groups. It was the major risk factor for infective endocarditis; and was the indication for valve surgery in 44 of 50 patients who had undergone valve replacement procedures. CONCLUSIONS: We acknowledge that rheumatic heart disease remains a leading cause of progressive and severe primary left-sided valve disease among young adults in Uganda. But we bring to light the contemporary footprints of other forms of primary valve disease that require coordinated multidisciplinary approach to research, education and clinical management to ensure improved patient outcomes.

Kidney disease in Uganda: a community based study.

BACKGROUND: Chronic kidney disease (CKD) is a major cause of morbidity and mortality in Sub-Saharan Africa (SSA). The majority of studies on CKD in SSA have been conducted among HIV-infected populations and mainly from large health facilities. We determined the prevalence of CKD and its predictors among populations in communities in central Uganda. METHODS: A cross-sectional study was conducted in Wakiso district using multi-stage sampling. Data was collected on age, sex, socio-economic status, history of alcohol intake, diabetes mellitus, hypertension and smoking. Measurement of blood pressure, weight and height to determine body mass index (BMI) and investigations including HIV testing, fasting blood sugar, creatinine and urinalysis were conducted. Logistic regression was used to estimate the strength of the association between variables and the presence of CKD estimated using the Cockcroft Gault formula. RESULTS: A total of 955 participants aged 18-87 years were enrolled into the study. The median age was 31 years (Interquartile range 24-42) and majority (67%) were female. Up to 21.4% (204/955) had abnormal renal function with CKD stage 1 in 6.2% (59/955), stage 2 in 12.7% (121/955), stage 3 in 2.4% (23/955), CKD stage 4 in 0% and CKD stage 5 in 0.1% (1/995). Female gender OR 1.8 (95% Confidence Interval [CI] 1.2-2.8), age >30 years OR 2.2(95% CI 1.2-3.8) and high social economic status OR 2.1 (95% CI 1.3-3.6) were associated with increased risk of CKD while BMI > 25Kg/m2 was protective against CKD OR 0.1 (95% CI 0.04-0.2). Traditional risk factors such as HIV-infection, diabetes mellitus, smoking and alcohol intake were not found to be significantly associated with CKD. CONCLUSION: We found a high prevalence of kidney disease in central Uganda. Interestingly the traditional risk factors associated with CKD previously documented, were not associated with CKD.

Role of Natural Autoantibodies in Ugandans With Rheumatic Heart Disease and HIV.

BACKGROUND: Rheumatic heart disease (RHD) and HIV are prevalent diseases in sub-Saharan Africa, but little is known about their potential interrelationships. The objective of this study was to assess the prevalence of protective natural autoantibodies among patients with RHD in Uganda, and to determine whether the levels of these autoantibodies are affected by HIV status. METHODS: Participants were grouped according to RHD and HIV status. The three control groups (RHD - HIV -, RHD - HIV +, RHD + HIV -) were age-matched to the RHD + HIV + participants. All participants underwent HIV testing and echocardiography to evaluate for RHD. Natural autoantibody levels reactive with phosphorylcholine (PC) and malondialdehyde (MDA) were measured. FINDINGS: We enrolled 220 participants; 21 with both RHD and HIV. Ages ranged from 10 to 60 years, with female predominance (144/220, 65%). After adjusting for age and gender, HIV infection and RHD were each associated with low IgM anti-PC (HIV: p < 0.0001 and RHD: p = 0.01). A distinct HIV ∗ RHD interaction was identified (p = 0.045) with increased IgG anti-MDA levels in HIV infected subjects without RHD, whereas IgG anti-MDA levels were decreased in HIV infected subjects with RHD. INTERPRETATION: We found that HIV and RHD are associated with alterations in natural autoantibody responses previously linked to an increased risk for atherosclerosis and autoimmune inflammatory disease.