Browsing by Author "Okello, Emmy"
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Item Comparison of approaches to determine echocardiographic outcomes for children with latent rheumatic heart disease(Open Heart, 2022) Rwebembera, Joselyn; Beaton, Andrea; Okello, Emmy; Nakitto, Miriam; Pulle, Jafesi; Scheel, Amy; Grobler, Anneke; Steer, Andrew Craig; Sable, CraigScreening programmes using echocardiography offer opportunity for intervention through identification and treatment of early (latent) rheumatic heart disease (RHD). We aimed to compare two methods for classifying progression or regression of latent RHD: serial review method and blinded, side-by-side review.Item Household Economic Consequences of Rheumatic Heart Disease in Uganda(Frontiers in Cardiovascular Medicine, 2021) Opara, Chinonso C.; Atala, Jenifer; Kansiime, Rosemary; Nakitto, Miriam; Ndagire, Emma; Nalubwama, Haddy; Okello, Emmy; Watkins, David A.; Su, YanfangRheumatic heart disease (RHD) has declined dramatically in wealthier countries in the past three decades, but it remains endemic in many lower-resourced regions and can have significant costs to households. The objective of this study was to quantify the economic burden of RHD among Ugandans affected by RHD.Item Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study(The Lancet Global Health, 2021) Okello, Emmy; Ndagire, Emma; Muhamed, Babu; Sarnacki, Rachel; Nakitto, M.G.; Kansiime, Rosemary; Longenecker, Chris T.; Lwabi, Peter; Agaba, Collins; Omara, Isaac Otim; Oyella, Linda Mary; Rwebembera, Joselyn; Watkins, David; Carapetis, Jonathan R.Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda. For our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3–17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5–14 years and characterised clinical features of definite and possible acute rheumatic fever cases. Data were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5–14 years as 25 cases (95% CI 13·7–30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1–21·0) per 100 000 person-years in Mbarara district (west).Item Meta-analysis of genome-wide association studies of stable warfarin dose in patients of African ancestry(Elsevier Inc, 2024-10-20) Asiimwe, Innocent G; Blockman, Marc; Cavallari, Larisa H; Cohen, Karen; Cupido, Clint; Dandara, Collet; Davis, Brittney H; Jacobson, Barry; Johnson, Julie A; Lamorde, Mohammed; Limdi, Nita A; Morgan, Jennie; Mouton, Johannes P; Muyambo, Sarudzai; Nakagaayi, Doreen; Ndadza, Arinao; Okello, Emmy; Perera, Minoli A; Schapkaitz, Elise; Sekaggya-Wiltshire, Christine; Semakula, Jerome R; Tatz, Gayle; Waitt, Catriona; Yang, Guang; Zhang, Eunice J; Jorgensen, Andrea L; Pirmohamed, MunirWarfarin dose requirements are highly variable because of clinical and genetic factors. Although genetic variants influencing warfarin dose have been identified in European and East Asian populations, more work is needed to identify African-specific genetic variants to help optimize warfarin dosing. We performed genome-wide association studies (GWASs) in 4 African cohorts from Uganda, South Africa, and Zimbabwe, totaling 989 warfarin-treated participants who reached stable dose and had international normalized ratios within therapeutic ranges. We also included 2 African American cohorts recruited by the International Warfarin Pharmacogenetics Consortium (n = 316) and the University of Alabama at Birmingham (n = 199). After the GWAS, we performed standard error-weighted meta-analyses and then conducted stepwise conditional analyses to account for known loci in chromosomes 10 and 16. The genome-wide significance threshold was set at P < 5 × 10-8. The meta-analysis, comprising 1504 participants, identified 242 significant SNPs across 3 genomic loci, with 99.6% of these located within known loci on chromosomes 10 (top SNP: rs58800757, P = 4.27 × 10-13) and 16 (top SNP: rs9925964, P = 9.97 × 10-16). Adjustment for the VKORC1 SNP -1639G>A revealed an additional locus on chromosome 2 (top SNPs rs116057875/rs115254730/rs115240773, P = 3.64 × 10-8), implicating the MALL gene, that could indirectly influence warfarin response through interactions with caveolin-1. In conclusion, we reaffirmed the importance of CYP2C9 and VKORC1 in influencing warfarin dose requirements, and identified a new locus (MALL), that still requires direct evidence of biological plausibility.ABSTRACTWarfarin dose requirements are highly variable because of clinical and genetic factors. Although genetic variants influencing warfarin dose have been identified in European and East Asian populations, more work is needed to identify African-specific genetic variants to help optimize warfarin dosing. We performed genome-wide association studies (GWASs) in 4 African cohorts from Uganda, South Africa, and Zimbabwe, totaling 989 warfarin-treated participants who reached stable dose and had international normalized ratios within therapeutic ranges. We also included 2 African American cohorts recruited by the International Warfarin Pharmacogenetics Consortium (n = 316) and the University of Alabama at Birmingham (n = 199). After the GWAS, we performed standard error-weighted meta-analyses and then conducted stepwise conditional analyses to account for known loci in chromosomes 10 and 16. The genome-wide significance threshold was set at P < 5 × 10-8. The meta-analysis, comprising 1504 participants, identified 242 significant SNPs across 3 genomic loci, with 99.6% of these located within known loci on chromosomes 10 (top SNP: rs58800757, P = 4.27 × 10-13) and 16 (top SNP: rs9925964, P = 9.97 × 10-16). Adjustment for the VKORC1 SNP -1639G>A revealed an additional locus on chromosome 2 (top SNPs rs116057875/rs115254730/rs115240773, P = 3.64 × 10-8), implicating the MALL gene, that could indirectly influence warfarin response through interactions with caveolin-1. In conclusion, we reaffirmed the importance of CYP2C9 and VKORC1 in influencing warfarin dose requirements, and identified a new locus (MALL), that still requires direct evidence of biological plausibility. MEDLINE - AcademicItem Outcomes of rheumatic fever in Uganda: a prospective cohort study(Elsevier Ltd, 2024-03) Wirth, Scott H; Pulle, Jafesi; Seo, JangDong; Ollberding, Nicholas J; Nakagaayi, Doreen; Sable, Craig; Bowen, Asha C; Parks, Tom; Carapetis, Jonathan; Okello, Emmy; Beaton, Andrea; Ndagire, EmmaAbstract Rheumatic heart disease is the largest contributor to cardiac-related mortality in children worldwide. Outcomes in endemic settings after its antecedent illness, acute rheumatic fever, are not well understood. We aimed to describe 3-5 year mortality, acute rheumatic fever recurrence, changes in carditis, and correlates of mortality after acute rheumatic fever. We conducted a prospective cohort study of Ugandan patients aged 4-23 years who were diagnosed with definite acute rheumatic fever using the modified 2015 Jones criteria from July 1, 2017, to March 31, 2020, enrolled at three rheumatic heart disease registry sites in Uganda (in Mbarara, Mulago, or Lira), and followed up for at least 1 year after diagnosis. Patients with congenital heart disease were excluded. Patients underwent annual review, most recently in August, 2022. We calculated rates of mortality and acute rheumatic fever recurrence, tabulated changes in carditis, performed Kaplan-Meier survival analyses, and used Cox regression models to identify correlates of mortality. Data were collected between Sept 1 and Sept 30, 2022. Of 182 patients diagnosed with definite acute rheumatic fever, 156 patients were included in the analysis. Of these 156 patients (77 [49%] male and 79 (51%) female; data on ethnicity not collected), 25 (16%) died, 21 (13%) had a cardiac-related death, and 17 (11%) had recurrent acute rheumatic fever over a median of 4·3 (IQR 3·0-4·8) years. 16 (24%) of the 25 deaths occurred within 1 year. Among 131 (84%) of 156 survivors, one had carditis progression by echo. Moderate-to-severe carditis (hazard ratio 12·7 [95% CI 3·9-40·9]) and prolonged PR interval (hazard ratio 4·4 [95% CI 1·7-11·2]) at acute rheumatic fever diagnosis were associated with increased cardiac-related mortality. These are the first contemporary data from sub-Saharan Africa on medium-term acute rheumatic fever outcomes. Mortality rates exceeded those reported elsewhere. Most decedents already had chronic carditis at initial acute rheumatic fever diagnosis, suggesting previous undiagnosed episodes that had already compounded into rheumatic heart disease. Our data highlight the large burden of undetected acute rheumatic fever in these settings and the need for improved awareness of and diagnostics for acute rheumatic fever to allow earlier detection. Strauss Award at Cincinnati Children's Hospital, American Heart Association, and Wellcome Trust.Item Prevalence and pattern of echocardiographic abnormalities among patients on haemodialysis at an urban hospital in Central Uganda(African Journal of Nephrology, 2020) Kansiime, Grace; Kalyesubula, Robert; Okello, Emmy; Ocama, PonsianoCardiovascular disease is the most common cause of morbidity and premature mortality in patients on chronic haemodialysis. There are limited data on cardiac abnormalities among these patients in sub-Saharan Africa, including Uganda. We determined the prevalence and patterns of echocardiographic (echo) abnormalities among patients with end-stage renal disease (ESRD) on haemodialysis at Mulago National Referral Hospital, Kampala, Uganda. Methods: Eighty patients with ESRD on chronic haemodialysis were enrolled in the study over a period of five months from November 2017 to March 2018. We collected data on demographic and baseline clinical characteristics by reviewing charts and conducting patient interviews. Participants had blood pressure measurements performed and blood samples taken for laboratory investigations. We then conducted a cardiac evaluation using standard transthoracic echo protocols. Bivariable and multivariable analysis was performed to study associations with left ventricular hypertrophy and diastolic dysfunction. Results: Fifty-three of the 80 patients (66%) were male, mean age was 49 ± 16 years and the median duration on dialysis was 9.5 months (interquartile range 4–24 months). Twenty-eight (35%) had to travel >50 km to access dialysis. Seventy-four patients (93%) had at least one cardiac echo abnormality and 30% had at least three abnormalities. Left ventricular hypertrophy (68%) and diastolic dysfunction (64%) were the most common abnormalities. There was a high prevalence of factors that have previously been associated with left ventricular hypertrophy and diastolic dysfunction including anaemia (79%), poorly controlled hypertension (79%) and dyslipidaemia (56%) but none of these was statistically significantly associated in this study. Conclusions: Our study confirmed a high prevalence of cardiac abnormalities among a young population of African patients with ESRD on chronic dialysis. We recommend that echocardiography be part of the routine care to help plan early intervention for those at high risk of cardiovascular events.Item Prevalence of cardiovascular risk factors in active tuberculosis in Africa: a systematic review and meta‑analysis(Scientific Reports, 2022) Baruch Baluku, Joseph; Ronald, Olum; 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. Costeffective strategies are needed to screen for CVR factors among people with active TB in Africa.Item Prevalence of group a streptococcus pharyngeal carriage and clinical manifestations in school children aged 5–15 yrs in Wakiso District, Uganda(BMC Infectious Diseases, 2017) Nayiga, Irene; Okello, Emmy; Lwabi, Peter; Ndeezi, GraceBeta-hemolytic streptococci carrier rates in children living in low-income countries are high ranging from 10 to 50%. Although most of these children are asymptomatic, they are a reservoir and pose a risk of transmission. The aim of this study was to determine the prevalence of group a streptococcus pharyngeal carriage and clinical manifestations in school going children in Wakiso district, Uganda.A cross sectional study targeting children age 5–15 years in primary schools in one sub-county of Wakiso district was carried out. Three hundred and sixty-six children from five primary schools were enrolled and evaluated for group a streptococcus (GAS) carriage. A semi-structured questionnaire was used to collect data that included social demographics, school environment and clinical findings. For every enrolled child a throat swab was taken and cultured for GAS and blood was drawn for anti-streptolysin-O titres. Analysis of data was done using STATA.The prevalence of GAS carriage was 16%. The children with GAS positive cultures were mainly females. The factor associated with GAS carriage was the school location, with peri-urban schools more likely to have children with GAS compared to rural schools; AOR 2.48 (95% CI: 1.01 – 6.11), P = 0.049. There was no significant difference between the characteristic of children with GAS positive verses GAS negative throat swab cultures.There is a high prevalence of GAS pharyngeal carriage among children aged 5–15 years attending primary schools in Wakiso District, Uganda.Item Prevalence of latent rheumatic heart disease among HIV-infected children in Kampala, Uganda(Journal of acquired immune deficiency syndromes, 2016) Gleason, Brigette; Mirembe, Grace; Namuyonga, Judith; Okello, Emmy; Lwabi, Peter; Lubega, Irene; Lubega, Sulaiman; Musiime, Victor; Kityo, Cissy; Salata, Robert A.; Longenecker, Chris T.Rheumatic heart disease (RHD) remains highly prevalent in resource-constrained settings around the world, including countries with high rates of HIV/AIDS. Although both are immune-mediated diseases, it is unknown whether HIV modifies the risk or progression of RHD. We performed screening echocardiography to determine the prevalence of latent rheumatic heart disease in 488 HIV-infected children aged 5-18 in Kampala, Uganda. The overall prevalence of borderline/definite RHD was 0.82% (95% CI 0.26% to 2.23%) which is lower than the published prevalence rates of 1.5-4% among Ugandan children. There may be protective factors that decrease the risk of RHD in HIV-infected children.Item A Qualitative Study of Patients’ Experiences, Enablers and Barriers of Rheumatic Heart Disease Care in Uganda(Global Heart, 2023) Nalubwama, Hadija; Pulle, Jafesi; Atala, Jenifer; Nakitto, Miriam; Namara, Rebecca; Beaton, Andrea; Kansiime, Rosemary; Mwima, Rachel; Ndagire, Emma; Okello, Emmy; Watkins, DavidRheumatic heart disease (RHD) remains a significant public health problem in countries with limited health resources. People living with RHD face numerous social challenges and have difficulty navigating ill-equipped health systems. This study sought to understand the impact of RHD on PLWRHD and their households and families in Uganda. In this qualitative study, we conducted in-depth interviews with 36 people living with RHD sampled purposively from Uganda’s national RHD research registry, stratifying the sample by geography and severity of disease. Our interview guides and data analysis used a combination of inductive and deductive methods, with the latter informed by the socio-ecological model. We ran thematic content analysis to identify codes that were then collapsed into themes. Coding was done independently by three analysts, who compared their results and iteratively updated the codebook. The inductive portion of our analysis, which focused on the patient experience, revealed a significant impact of RHD on work and school. Participants often lived in fear of the future, faced limited childbirth choices, experienced domestic conflict, and suffered stigmatization and low self-esteem. The deductive portion of our analysis focused on barriers and enablers to care. Major barriers included the high out-of-pocket cost of medicines and travel to health facilities, as well as poor access to RHD diagnostics and medications. Major enablers included family and social support, financial support within the community, and good relationships with health workers, though this varied considerably by location. Despite several personal and community factors that support resilience, PLWRHD in Uganda experience a range of negative physical, emotional, and social consequences from their condition. Greater investment is needed in primary healthcare systems to support decentralized, patient-centered care for RHD. Implementing evidence-based interventions that prevent RHD at district level could greatly reduce the scale of human suffering. There is need to increase investment in primary prevention and tackling social determinants, to reduce the incidence of RHD in communities where the condition remains endemic.Item Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease(New England Journal of Medicine, 2022) Beaton, Andrea; Okello, Emmy; Rwebembera, Joselyn; Alepere, Juliet; Lwabi, Peter; Nakitto, Miriam; Ndagire, Emma; Omara, Isaac O.; Karthikeyan, Ganesan; Steer, Andrew C.Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown.