Rheumatic heart disease in Uganda: the association between MHC class II HLA DR alleles and disease: a case control study.

BACKGROUND: Rheumatic heart disease (RHD), the only long term consequence of acute rheumatic fever, remains a leading cause of morbidity and mortality among young adults in Uganda. An inherited susceptibility to acute rheumatic fever centers around the major histocompatibility class II human leucocyte antigens. However, there is paucity of data from sub-Saharan Africa. This study compares the frequency of HLA class II DR alleles between RHD cases and normal controls in Uganda. METHODS: One hundred ninety-nine participants including 96 established RHD cases aged 5-60 years and 103 age and sex matched normal controls were recruited for participation. DNA was manually extracted from buffy coat samples and HLA analysis was performed. HLA-DR allelic frequency comparison between cases and controls were estimated using conditional logistic regression with 95% confidence intervals. P -values were corrected for multiple hypothesis testing. RESULTS: 199 participants (103 female, 51.8%) completed the study. The mean (SD) age in years for cases and controls were 29.6 (10.2) and 29(18), respectively. After conditional logistic regression and multiple hypothesis testing, HLA-DR1was associated with a decreased risk of RHD (OR = 0.42, CI 0.21-085, P = 0.01, Corrected P value (PC) = 0.09,) while HLA-DR11 was associated with increased risk of RHD (OR = 3.31, CI 1.57-6.97, P = <0.001, Pc < 0.001). No other significant associations were found. CONCLUSION: In this first study of HLA genetic susceptibility to RHD in Uganda, HLA- DR1 was more common in normal controls while HLA- DR11 was more common among RHD cases suggesting a disease susceptibility association. In future studies, high resolution HLA analysis and genome wide studies should be carried out to confirm this pattern.

Socioeconomic and environmental risk factors among rheumatic heart disease patients in Uganda.

BACKGROUND: Although low socioeconomic status, and environmental factors are known risk factors for rheumatic heart disease in other societies, risk factors for rheumatic heart disease remain less well described in Uganda. AIMS AND OBJECTIVE: The objective of this study was to investigate the role of socio-economic and environmental factors in the pathogenesis of rheumatic heart disease in Ugandan patients. METHODS: This was a case control study in which rheumatic heart disease cases and normal controls aged 5-60 years were recruited and investigated for socioeconomic and environmental risk factors such as income status, employment status, distance from the nearest health centre, number of people per house and space area per person. RESULTS: 486 participants (243 cases and 243 controls) took part in the study. Average age was 32.37+/-14.6 years for cases and 35.75+/-12.6 years for controls. At univariate level, Cases tended to be more overcrowded than controls; 8.0+/-3.0 versus 6.0+/-3.0 persons per house. Controls were better spaced at 25.2 square feet versus 16.9 for cases. More controls than cases were employed; 45.3% versus 21.1%. Controls lived closer to health centers than the cases; 4.8+/-3.8 versus 3.3+/-12.9 kilometers. At multivariate level, the odds of rheumatic heart disease was 1.7 times higher for unemployment status (OR = 1.7, 95% CI = 1.05-8.19) and 1.3 times higher for overcrowding (OR = 1.35, 95% CI = 1.1-1.56). There was interaction between overcrowding and longer distance from the nearest health centre (OR = 1.20, 95% CI = 1.05-1.42). CONCLUSION: The major findings of this study were that there was a trend towards increased risk of rheumatic heart disease in association with overcrowding and unemployment. There was interaction between overcrowding and distance from the nearest health center, suggesting that the effect of overcrowding on the risk of acquiring rheumatic heart disease increases with every kilometer increase from the nearest health center.

Adherence to antiretroviral therapy in HIV-positive adolescents in Uganda assessed by multiple methods: a prospective cohort study.

BACKGROUND: The effectiveness of traditional adherence measurements used in adolescent populations is difficult to assess. Antiretroviral (ARV) adherence research among adolescents living with HIV in resource-constrained countries is particularly challenging and little evidence is available. OBJECTIVES: The primary objective of this study was to determine the feasibility of a large-scale, long-term study using electronic adherence monitoring in Uganda. The secondary objective was to compare accuracy of pill count (PC) and self-report (SR) adherence with electronic medication vials (eCAPs™). METHODS: Adolescents receiving ARV therapy at the Joint Clinical Research Centre in Kampala, Uganda, were recruited. ARVs were dispensed in eCAPs™ for 1 year. Person-pill-days (PPDs) [1 day where adherence was measured for one medication in one patient] were calculated and a weighted paired t-test was used to compare the levels of adherence among subjects for three different adherence measurement methods. RESULTS: Fifteen patients were included: 40% were female, mean age was 14 years, mean baseline CD4+ cell count was 244 cells/µL, and average treatment duration was 9 months at study entry. Overall, 4721 PPDs were observed. Some eCAPs™ required replacement during the study resulting in some data loss. Consent rate was high (94%) but was slow due to age limit cut-points. Overall adherence for SR was 99%, PC was 97% and eCAP™ was 88% (p<0.05 for all comparisons). 93%, 67% and 23% of patients had an adherence of greater than 95% as measured by SR, PC and eCAP™ methods, respectively. CONCLUSIONS: A large-scale adherence study in Uganda would be feasible using a more robust electronic monitoring system. Adherence measurements produced by PCs and self-reporting methods appear to overestimate adherence measured electronically.

Existing capacity to manage pharmaceuticals and related commodities in East Africa: an assessment with specific reference to antiretroviral therapy.

BACKGROUND: East African countries have in the recent past experienced a tremendous increase in the volume of antiretroviral drugs. Capacity to manage these medicines in the region remains limited. Makerere University, with technical assistance from the USAID supported Rational Pharmaceutical Management Plus (RPM Plus) Program of Management Sciences for Health (MSH) established a network of academic institutions to build capacity for pharmaceutical management in the East African region. The initiative includes institutions from Uganda, Tanzania, Kenya and Rwanda and aims to improve access to safe, effective and quality-assured medicines for the treatment of HIV/AIDS, TB and Malaria through spearheading in-country capacity. The initiative conducted a regional assessment to determine the existing capacity for the management of antiretroviral drugs and related commodities. METHODS: Heads and implementing workers of fifty HIV/AIDS programs and institutions accredited to offer antiretroviral services in Uganda, Kenya, Tanzania and Rwanda were key informants in face-to-face interviews guided by structured questionnaires. The assessment explored categories of health workers involved in the management of ARVs, their knowledge and practices in selection, quantification, distribution and use of ARVs, nature of existing training programs, training preferences and resources for capacity building. RESULTS: Inadequate human resource capacity including, inability to select, quantify and distribute ARVs and related commodities, and irrational prescribing and dispensing were some of the problems identified. A competence gap existed in all the four countries with a variety of healthcare professionals involved in the supply and distribution of ARVs. Training opportunities and resources for capacity development were limited particularly for workers in remote facilities. On-the-job training and short courses were the preferred modes of training. CONCLUSION: There is inadequate capacity for managing medicines and related commodities in East Africa. There is an urgent need for training in aspects of pharmaceutical management to different categories of health workers. Skills building activities that do not take healthcare workers from their places of work are preferred.

Non-adherence to anti-TB drugs among TB/HIV co-infected patients in Mbarara Hospital Uganda: prevalence and associated factors.

BACKGROUND: Non-adherence to treatment remains a major obstacle to efficient tuberculosis control in developing countries. The dual infection of Tuberculosis and HIV presents further adherence problems because of high pill burden and adverse effects. This poses a risk of increased multi-drug resistant TB. However, the prevalence of non-adherence and its associated factors have not been studied in these patients in Uganda. OBJECTIVES: To determine the prevalence and factors associated with non-adherence to anti-TB drugs among TB/HIV co-infected patients in Mbarara hospital. METHODS: A cross-sectional study with qualitative and quantitative data collection methods was conducted among TB/HIV co-infected adults in Mbarara hospital from January to March 2008. Consecutive sampling was used to select 140 participants. Adherence was assessed over a 5-day period prior to the interview using patients self-reports. Data was collected using an interviewer administered questionnaire. Qualitative data was collected through key informant interviews using a topic guide and was analyzed manually. Quantitative data was analyzed using STATA version 8. Logistic regression was used to determine factors associated with nonadherence. RESULTS: The prevalence of non-adherence was 25% (95% CI=17.8-32%). Being on continuous phase of the TB regimen was significantly associated with non-adherence (OR=6.24, p<0.001). Alcohol consumption, being on antiretroviral therapy and smoking confounded the relationship between stage of the TB regimen and non-adherence. CONCLUSION: The prevalence of non-adherence was high. Patients that are on continuous phase of TB treatment should be supported to continue taking their drugs. In addition, patients that drink alcohol; smoke and those not on ART should be targeted with interventions to improve adherence.