Pharmaco-disparities in heart failure: a survey of the affordability of guideline recommended therapy in 10 countries.

AIMS: Heart failure with reduced ejection fraction (HFrEF) is treatable but guideline-directed medical therapy (GDMT) may not be affordable or accessible to people living with the disease. METHODS AND RESULTS: In this cross-sectional survey, we investigated the price, affordability, and accessibility of four pivotal classes of HFrEF GDMT: angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or angiotensin-neprilysin inhibitors (ARNI); beta-blockers; mineralocorticoid receptor antagonists (MRA); and sodium glucose co-transporter 2 inhibitors (SGLT2i). We sampled online or community pharmacies in 10 countries across a range of World Bank income groups, assessing mean 30 day retail prescription prices, affordability relative to gross national income per capita per month, and accessibility. We reported median price ratios relative to the International Reference Standard. We performed a literature review to evaluate accessibility to GDMT classes through publicly funded drug programmes in each country. HFrEF GDMT prices, both absolute and relative to the international reference, were highest in the United States and lowest in Pakistan and Bangladesh. The most expensive drug was the ARNI, sacubitril/valsartan, with a mean (standard deviation, SD) 30 day price ranging from $11.06 (0.81) in Pakistan to $611.50 (3.54) in United States. The least expensive drug was the MRA, spironolactone, with a mean (SD) 30 day price ranging from $0.18 (0.00) in Pakistan to $12.32 (0.00) in England. Affordability (SD) of quadruple therapy-ARNI, beta-blockers, MRA, and SGLT2i-was best in high-income and worst in low-income countries, ranging from 1.49 (0.00)% of gross national income per capita per month in England to 232.47 (31.47)% in Uganda. Publicly funded drug programmes offset costs for eligible patients, but ARNI and SGLT2i were inaccessible through these programmes in low- and middle-income countries. Price, affordability, and access were substantially improved in all countries by substituting ARNI for ACEi/ARB. CONCLUSIONS: There was marked variation between countries in the retail price of HFrEF GDMT. Despite higher prices in high-income countries, GDMT was more accessible and affordable than in low- and middle-income countries. Publicly funded drug programmes in lower income countries increased affordability but limited access to newer HFrEF GDMT classes. Pharmaco-disparities must be addressed to improve HFrEF outcomes globally.

Prevalence and factors associated with suboptimal blood pressure among ambulatory patients with diabetic kidney disease attending a tertiary hospital in Uganda.

Background: Kidney failure prevalence is increasing among diabetic kidney disease (DKD) patients in low-income countries. Suboptimal blood pressure (BP) drives kidney failure and mortality. The burden of suboptimal BP and its associated factors among these patients are not well documented. Objectives: To determine the prevalence of suboptimal BP and associated factors among those with DKD attending Kiruddu National Referral Hospital. Methods: In this cross-sectional study, recruited participants were screened for DKD using urine dipsticks from 6th May 2020 to 15th July 2020. A pretested questionnaire was administered, BP, height and weight were measured. Suboptimal BP was defined as systolic BP > 130mmHg and or diastolic BP > 80mmHg. A Poisson regression model analysed the associated factors. Results: 250 participants with DKD, mean age of 52(11) years were included of whom 199 (79.6%) were female. Suboptimal BP prevalence was 84.4%, associated with past (p = 0.04) and current (p < 0.001) alcohol use, overweight (p < 0.001) and obesity (p < 0.001), wage earning (p < 0.001) and professionals (p = 0.048). Conclusion: The prevalence of suboptimal BP was high among the overweight, obese, unemployed and alcohol users. Thus, there is a need for better BP control interventions.

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.

Cardiovascular diseases in Africa in the twenty-first century: Gaps and priorities going forward.

In 2015, the United Nations set important targets to reduce premature cardiovascular disease (CVD) deaths by 33% by 2030. Africa disproportionately bears the brunt of CVD burden and has one of the highest risks of dying from non-communicable diseases (NCDs) worldwide. There is currently an epidemiological transition on the continent, where NCDs is projected to outpace communicable diseases within the current decade. Unchecked increases in CVD risk factors have contributed to the growing burden of three major CVDs-hypertension, cardiomyopathies, and atherosclerotic diseases- leading to devastating rates of stroke and heart failure. The highest age standardized disability-adjusted life years (DALYs) due to hypertensive heart disease (HHD) were recorded in Africa. The contributory causes of heart failure are changing-whilst HHD and cardiomyopathies still dominate, ischemic heart disease is rapidly becoming a significant contributor, whilst rheumatic heart disease (RHD) has shown a gradual decline. In a continent where health systems are traditionally geared toward addressing communicable diseases, several gaps exist to adequately meet the growing demand imposed by CVDs. Among these, high-quality research to inform interventions, underfunded health systems with high out-of-pocket costs, limited accessibility and affordability of essential medicines, CVD preventive services, and skill shortages. Overall, the African continent progress toward a third reduction in premature mortality come 2030 is lagging behind. More can be done in the arena of effective policy implementation for risk factor reduction and CVD prevention, increasing health financing and focusing on strengthening primary health care services for prevention and treatment of CVDs, whilst ensuring availability and affordability of quality medicines. Further, investing in systematic country data collection and research outputs will improve the accuracy of the burden of disease data and inform policy adoption on interventions. This review summarizes the current CVD burden, important gaps in cardiovascular medicine in Africa, and further highlights priority areas where efforts could be intensified in the next decade with potential to improve the current rate of progress toward achieving a 33% reduction in CVD mortality.

Makerere University-Uganda Heart Institute collaborative cardiovascular disease training and research since 1988.

Background: Makerere University College of Health Sciences has been collaborating with the Uganda Heart Institute to build capacity for research, training and clinical care in cardiovascular medicine for the last 34 years to appropriately respond to rising societal needs for advanced cardiovascular care which was lacking before this period. Aim: To describe the major milestones in the MakCHS-UHI cardiovascular training collaboration and chart way for future collaborations. Method: This short communication highlights some of the salient features and important milestones in the collaboration journey of the two institutions. Conclusion: Clinical centres of excellence in specialised fields of health care, such as the Uganda Heart Institute for Cardiology, provide a conducive academic environment for MakCHS clinical scientists to provide high quality evidence-based care to meet societal needs.

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.

SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in a Child in Uganda: A Paediatric Experience in a Resource-Limited Setting.

SARS-CoV-2-associated Multisystem Inflammatory Syndrome in children (MIS-C) has been described in developed settings that have reported a high burden of COVID-19 cases. However, to date, there are few published cases of MIS-C that have been described in the African region. MIS-C has high morbidity and even mortality without a prompt diagnosis. We report a case of a 9-year-old girl who presented with typical clinical features of MIS-C in Uganda but had a delay in diagnosis. This case report aims to raise awareness among health providers in similar settings to improve clinical suspicion of MIS-C, facilitate prompt diagnosis and treatment, and thus improve outcomes.

Vitamin D and its association with symptom severity in knee osteoarthritis: a cross sectional study at a national referral hospital in Uganda.

BACKGROUND: Vitamin D deficiency is highly prevalent among patients with osteoarthritis. It is associated with joint pain, stiffness and worse physical function. Whether vitamin D deficiency is associated with osteoarthritis is controversial. We investigated serum vitamin D levels and its association with symptom severity in patients with knee osteoarthritis. METHODS: Between January 2020 to March and May 2020, we conducted a cross sectional study at a national referral hospital in Uganda. Using the American College of Rheumatology clinical criteria, 107 consenting adults were diagnosed with knee osteoarthritis. A questionnaire captured patient demographics and clinical characteristics. Joint pain, stiffness and physical function severity were assessed and graded based on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). We determined serum vitamin D levels by electrochemilumniscence immunoassay. The data were analysed and adjusted for age, sex, education, occupation, family history, body mass index (BMI) and calcium supplementation. RESULTS: Of the 107 patients, 92 (86%) patients were females, mean (SD) age was 58.1 (12.6) years. Nearly 65% of the patients had suboptimal serum vitamin D levels < 30 ng/ml. The median (Q1, Q3) WOMAC joint scores were as follows: pain 8.0 (5, 11), stiffness 1 (0, 2), physical function 29.0 (16, 41) and total WOMAC 39.0 (21, 54). Spearman correlations between serum vitamin D levels with symptom severity were as follows: joint pain (r = 0.18, p = 0.06), stiffness (r = 0.13, p = 0.17), physical function (r = 0.09, p = 0.36) and total WOMAC (r = 0.13, p = 0.19). CONCLUSION: Serum vitamin D levels are not associated with joint pain, stiffness and physical function severity. Older age and higher BMI are associated with vitamin D deficiency in patients with knee osteoarthritis attending a national referral hospital rheumatology clinic in Uganda. Suboptimal vitamin D is an independent risk factor for total mortality in the general population. Clinical guidelines and further studies to determine age and BMI ranges required for vitamin D screening are needed in patients with osteoarthritis in Uganda. Patients are advised to keep a normal BMI.

Safety and efficacy of hydroxychloroquine for treatment of non-severe COVID-19 among adults in Uganda: a randomized open label phase II clinical trial.

BACKGROUND: Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. DESIGN: We conducted a randomized open label Phase II clinical trial from October-December 2020. METHODS: Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. RESULTS: Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3-4) vs 4(2-4): p = 0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. CONCLUSION: Our results show that HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution among adults with COVID-19 in Uganda. TRIAL REGISTRATION:  NCT04860284.

Rational and design of SATRACD study: detecting subclinical anthracycline therapy related cardiac dysfunction in low income country.

BACKGROUND: Anthracycline therapy-related cardiac dysfunction (ATRCD) is the most notorious adverse side-effect of chemotherapy. It has become a significant cardiovascular health concern for long-term cancer survivors. With the emerging concept of subclinical ATRCD and newer diagnostictools (Speckle Tracking Echocardiography (STE) and biomarkers), detecting anthracycline cardiac toxicity at an early stage has become an important step to prevent severe cardiac dysfunction and improve the cardiovascular outcome in cancer survivors. Despite the increasing population at risk in sub-Saharan Africa (SSA), there is no contemporary data in Uganda to address the burden, pathogenesis and risk factors of subclinical ATRCD. This big gap in knowledge has led to a lack of local guidelines for monitoring and management of ATRCD. METHODS: SATRACD (Detecting Subclinical Anthracycline Therapy Related Cardiac Dysfunction In Low Income Country) study is an observational prospective cohort study. Three hundred and fifty-three anthracycline naïve cancer patients will be recruited at baseline. Patients are followed up on completion of anthracycline-based chemotherapy and at 6 months after completion of anthracycline therapy. Data on demographics, cancer profile and clinical presentation will be collected at baseline. Comprehensive cardiac assessment will be performed at each visit, including electrocardiogram, conventional echocardiography, STE, cardiac and oxidative stress markers. We will be able to determine the incidence of subclinical and clinical ATRCD at 6 months after completion of anthracycline therapy, determine whether hypertension is a major risk factor for ATRCD, evaluate the role of conventional echocardiography parameters, and biomarkers for detecting subclinical ATRCD. CONCLUSION: This SATRACD study will provide contemporary data on Ugandan cancer patients who have subclinical and clinical ATRCD, help in the development of local strategies to prevent and manage ATRCD, and improve cardiovascular outcome for Ugandan cancer survivors.

High prevalence of non-dipping patterns among Black Africans with uncontrolled hypertension: a secondary analysis of the CREOLE trial.

BACKGROUND: Dipping of blood pressure (BP) at night is a normal physiological phenomenon. However, a non-dipping pattern is associated with hypertension mediated organ damage, secondary forms of hypertension and poorer long-term outcome. Identifying a non-dipping pattern may be useful in assessing risk, aiding the decision to investigate for secondary causes, initiating treatment, assisting decisions on choice and timing of antihypertensive therapy, and intensifying salt restriction. OBJECTIVES: To estimate the prevalence and factors associated with non-dipping pattern and determine the effect of 6 months of three antihypertensive regimens on the dipping pattern among Black African hypertensive patients. METHODS: This was a secondary analysis of the CREOLE Study which was a randomized, single blind, three-group trial conducted in 10 sites in 6 Sub-Saharan African countries. The participants were 721 Black African patients, aged between 30 and 79 years, with uncontrolled hypertension and a baseline 24-h ambulatory blood pressure monitoring (ABPM). Dipping was calculated from the average day and average night systolic blood pressure measures. RESULTS: The prevalence of non-dipping pattern was 78% (564 of 721). Factors that were independently associated with non-dipping were: serum sodium > 140 mmol/l (OR = 1.72, 95% CI 1.17-2.51, p-value 0.005), a higher office systolic BP (OR = 1.03, 95% CI 1.01-1.05, p-value 0.003) and a lower office diastolic BP (OR = 0.97, 95% CI 0.95-0.99, p-value 0.03). Treatment allocation did not change dipping status at 6 months (McNemar's Chi2 0.71, p-value 0.40). CONCLUSION: There was a high prevalence of non-dipping among Black Africans with uncontrolled hypertension. ABPM should be considered more routinely in Black Africans with uncontrolled hypertension, if resources permit, to help personalise therapy. Further research is needed to understand the mechanisms and causes of non-dipping pattern and if targeting night-time BP improves clinical outcomes. Trial registration ClinicalTrials.gov (NCT02742467).

Clinical characterization, cardiovascular risk factor profile and cardiac strain analysis in a Uganda cancer population: The SATRACD study.

BACKGROUND: The link between cancer and cardiovascular disease is firmly established. We sought to investigate the prevalence of cardiovascular disease (CVD) risk factors in Uganda cancer patients, their pre-chemotherapy left ventricular strain echocardiographic pattern and its associations with the CVD risk factors. METHODS AND RESULTS: Baseline pre-chemotherapy data of patients who were enrolled in the SATRACD study (a cancer cohort, who were planned for anthracycline therapy), were analyzed. The prevalence of cardiovascular risk factors and baseline strain echocardiographic images were assessed. Among the 355 patients who were recruited over a period of 15 months, 283 (79.7%) were female, with a mean age of 43 years. The types of cancer of the study patients included breast cancer (70.6%), lymphomas, sarcomas, leukemias and hepatocellular carcinoma. Hypertension was the most common comorbidity (27.0%). The prevalence of obesity was 12.1% and that of HIV was 18.3%. All patients had a normal left ventricular ejection fraction (LVEF). The mean global longitudinal strain (GLS) was -20.92 ±2.43%, with females having a significantly higher GLS than males (-21.09±2.42 vs -20.25±2.39, p = 0.008). Fifty-three patients (14.9%) had suboptimal GLS (absolute GLS≤18.00%), which was associated with obesity (POR = 3.07; 95% CI, 1.31-6.98; p = 0.003), alcohol use (POR = 1.94; 95% CI, 1.01-3.74; p = 0.044), long QTc interval in electrocardiogram (POR = 2.54; 95% CI, 1.06-5.74; p = 0.015,) and impaired left ventricular relaxation (POR = 2.24; 95% CI, 1.17-4.25; p = 0.007). On multivariable logistic regression analysis, obesity (POR = 2.95; 95% CI, 1.24-7.03; p = 0.014) was the only independent factor associated with suboptimal GLS. CONCLUSION: There is high prevalence and a unique pattern of cardiovascular risk factors in Uganda cancer patients. In cancer patients with cardiovascular risk conditions, there is reduction in GLS despite preserved LVEF. Longitudinal research is needed to study the predictive value of cardiovascular risk factors and baseline GLS for post chemotherapy cardiac dysfunction.

Starting and Operating a Public Cardiac Catheterization Laboratory in a Low Resource Setting: The Eight-Year Story of the Uganda Heart Institute Catheter Laboratory.

Background: Low- and-middle-income-countries (LMICs) currently bear 80% of the world's cardiovascular disease (CVD) mortality burden. The same countries are underequipped to handle the disease burden due to critical shortage of resources. Functional cardiac catheterization laboratories (cath labs) are central in the diagnosis and management of CVDs. Yet, most LMICs, including Uganda, fall remarkably below the minimum recommended standards of cath lab:population ratio due to a host of factors including the start-up and recurring costs. Objectives: To review the performance, challenges and solutions employed, lessons learned, and projections for the future for a single cath lab that has been serving the Ugandan population of 40 million people in the past eight years. Methods: A retrospective review of the Uganda Heart Institute cath lab clinical database from 15 February 2012 to 31 December 2019 was performed. Results: In the initial two years, this cath lab was dependent on skills transfer camps by visiting expert teams, but currently, Ugandan resident specialists independently operate this lab. 3,542 adult and pediatric procedures were conducted in 8 years, including coronary angiograms and percutaneous coronary interventions, device implantations, valvuloplasties, and cardiac defect closures, among others. There was a consistent expansion of the spectrum of procedures conducted in this cath lab each year. The initial lack of technical expertise and sourcing for equipment, as well as the continual need for sundries present(ed) major roadblocks. Government support and leveraging existing multi-level collaborations has provided a platform for several solutions. Sustainability of cath lab services remains a significant challenge especially in relation to the high cost of sundries and other consumables amidst a limited budget. Conclusion: A practical example of how centers in LMIC can set up and sustain a public cardiac catheterization laboratory is presented. Government support, research, and training collaborations, if present, become invaluable leverage opportunities.

Burden, predictors and short-term outcomes of peripartum cardiomyopathy in a black African cohort.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with acute heart failure during the peripartum period. It is common in patients of African ancestry. Currently, there is paucity of data on the burden, predictors and outcomes of PPCM in Uganda. This study aimed to investigate the prevalence, predictors and six-month outcomes of PPCM in an adult cohort attending a tertiary specialised cardiology centre in Kampala, Uganda. METHODS: This study consecutively enrolled 236 women presenting with features of acute heart failure in the peripartum period. Clinical evaluation and echocardiography were performed on all the enrolled women. PCCM was defined according to recommendations of the Heart Failure Association of the European Society of Cardiology Working Group on PPCM. Poor outcome at six months of follow-up was defined as presence of any of the following: death of a mother or her baby, New York Heart Association (NYHA) functional class III-IV or failure to achieve complete recovery of left ventricular function (left ventricular ejection fraction ≤55%). RESULTS: The median age, BMI and parity of the study participants was 31.5 (25.5-38.0) years, 28.3 (26.4-29.7) and 3 (2-4) respectively. The prevalence of PPCM was 17.4% (n = 41/236). Multiple pregnancy was the only predictor of PPCM in this study population (OR 4.3 95% CI 1.16-16.05, p = 0.029). Poor outcome at six-months was observed in about 54% of the patients with PPCM (n = 4, 9.8% in NYHA functional class III-IV and n = 22, 53.7% with LVEF <55%). No maternal or foetal mortality was documented. CONCLUSION: PPCM is relatively common in Uganda and is associated with multiple pregnancy. Poor outcomes especially absence of complete recovery of left ventricular function are also common. Large studies to further investigate long-term maternal and foetal outcomes in Uganda are justified.

The spatial epidemiology of leprosy in Kenya: A retrospective study.

BACKGROUND: Leprosy elimination defined as a registered prevalence rate of less than 1 case per 10,000 persons was achieved in Kenya at the national level in 1989. However, there are still pockets of leprosy in some counties where late diagnosis and consequent physical disability persist. The epidemiology of leprosy in Kenya for the period 2012 through to 2015 was defined using spatial methods. METHODS: This was a retrospective ecological correlational study that utilized leprosy case based data extracted from the National Leprosy Control Program database. Geographic information system and demographic data were obtained from Kenya National Bureau of Statistics (KNBS). Chi square tests were carried out to check for association between sociodemographic factors and disease indicators. Two Spatial Poisson Conditional Autoregressive (CAR) models were fitted in WinBUGS 1.4 software. The first model included all leprosy cases (new, retreatment, transfers from another health facility) and the second one included only new leprosy cases. These models were used to estimate leprosy relative risks per county as compared to the whole country i.e. the risk of presenting with leprosy given the geographical location. PRINCIPAL FINDINGS: Children aged less than 15 years accounted for 7.5% of all leprosy cases indicating active leprosy transmission in Kenya. The risk of leprosy notification increased by about 5% for every 1 year increase in age, whereas a 1% increase in the proportion of MB cases increased the chances of new leprosy case notification by 4%. When compared to the whole country, counties with the highest risk of leprosy include Kwale (relative risk of 15), Kilifi (RR;8.9) and Homabay (RR;4.1), whereas Turkana had the lowest relative risk of 0.005. CONCLUSION: Leprosy incidence exhibits geographical variation and there is need to institute tailored local control measures in these areas to reduce the burden of disability.

Correction: Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

[This corrects the article DOI: 10.1371/journal.pgen.1006728.].

Modifiable lifestyle risk factors for stroke among a high risk hypertensive population in Greater Kampala, Uganda; a cross-sectional study.

OBJECTIVE: To describe the modifiable lifestyle risk factors for stroke among a high risk population for stroke. Africa suffers from rapid population growth, adoption of harmful western diets, and increased prevalence of hypertension and obesity. RESULTS: A total of 440 study participants were screened and 87 individuals with hypertension plus at least one other known stroke risk factor were enrolled. The prevalence of hypertension and diabetes mellitus in the screened population was 19.7 and 1.8%, respectively. Among those with hypertension only 2.3% (2/87) had ever had serum lipid assessment. Seventy-two percent (68/87) had very high serum LDL-cholesterol, while 33.3% (29/87) had low levels of HDL-cholesterol, and 67.8% had mean blood pressures greater than 160/100 mmHg and 40% (35/87) were obese, with a BMI ≥30. Targeting individuals with modifiable stroke risk factors and implementing self-management programs may be a way to reduce stroke burden in Uganda.

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

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.