Browsing by Author "Kakuhikire, Bernard"
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Item Adverse childhood experiences and adult cardiometabolic risk factors and disease outcomes: Cross-sectional, populationbased study of adults in rural Uganda(Journal of global health, 2021) Wooyoung Kim, Andrew; Kakuhikire, Bernard; Baguma, Charles; North, Crystal M.; Satinsky, Emily N.; Perkins, Jessica M.; Ayebare, Patience; Kiconco, Allen; Namara, Elizabeth B.; Bangsberg, David R.; Siedner, Mark J.Cardiovascular diseases (CVD) pose a major threat to public health in sub-Saharan African communities, where the burden of these classes of illnesses is expected to double by 2030. Growing research suggests that past developmental experiences and early life conditions may also elevate CVD risk throughout the life course. Greater childhood stress and adversity are consistently associated with a range of adult CVDs and associated risk factors, yet little research exists on the long-term effects of early life stress on adult physical health outcomes, especially CVD risk, in sub-Saharan African contexts. This study aims to evaluate the associations between adverse childhood experiences and adult cardiometabolic risk factors and health outcomes in a population-based study of adults living in Mbarara, a rural region of southwestern Uganda.Item Adverse childhood experiences, adult depression, and suicidal ideation in rural Uganda: A cross-sectional, population-based study(PLoS Med, 2021) Satinsky, Emily N.; Kakuhikire, Bernard; Baguma, Charles; Rasmussen, Justin D.; Ashaba, Scholastic; Cooper-Vince, Christine E.; Perkins, Jessica M.; Kiconco, Allen; Namara, Elizabeth B.; Bangsberg, David R.; Tsai, Alexander C.Depression is recognized globally as a leading cause of disability. Early-life adverse childhood experiences (ACEs) have been shown to have robust associations with poor mental health during adulthood. These effects may be cumulative, whereby a greater number of ACEs are progressively associated with worse outcomes. This study aimed to estimate the associations between ACEs and adult depression and suicidal ideation in a cross-sectional, population-based study of adults in Uganda.Item Association of Gut Intestinal Integrity and Inflammation with Insulin Resistance in Adults Living with HIV in Uganda(AIDS Patient Care and STDs, 2019) Reid, Michael J.A.; Ma, Yifei; Golovaty, Iya; Okello, Samson; Sentongo, Ruth; Feng, Maggie; Tsai, Alexander C.; Kakuhikire, Bernard; Tracy, Russell; Hunt, Peter W.; Siedner, Mark; Tien, Phyllis C.We conducted a cross-sectional study of 148 HIV+ on HIV antiretroviral therapy and 149 HIV- adults in Mbarara, Uganda, to estimate the association between HIV infection and homeostasis model assessment of insulin resistance (HOMA-IR) using multivariable regression analysis. In addition, we evaluated whether intestinal fatty acid-binding protein (I-FABP), monocyte activation markers soluble (s)CD14 and sCD163, and proinflammatory cytokine interleukin 6 (IL-6) mediated this association. HOMA-IR was greater among HIV+ than HIV- adults [median (interquartile range): 1.3 (0.7–2.5) vs. 0.9 (0.5–2.4); p = 0.008]. In models adjusted for sociodemographic variables, diet, hypertension, and smoking history, HIV infection was associated with 37% [95% confidence intervals (95% CIs): 5–77] greater HOMA-IR compared with HIV- participants. The magnitude of association was greater when I-FABP was included as a covariate although the additive effect was modest (40% CI: 8–82). By contrast adding sCD14 to the model was associated with greater HOMA-IR (59%; 95% CI: 21–109) among HIV+ participants compared with HIV- participants. Among HIV+ participants, greater CD4 nadir was non-significantly associated with greater HOMA-IR (22%; 95% CI: -2 to 52). Each 5-unit increase in body mass index (BMI; 49% greater HOMA-IR; 95% CI: 18–87) and female sex (71%; 95% CI: 17–150) remained associated in adjusted models. In this study of mainly normal-weight Ugandan adults, HIV infection, female sex, and greater BMI were all associated with greater insulin resistance (IR). This association was strengthened modestly after adjustment for sCD14, suggesting possible distinct immune pathways to IR that are independent of HIV or related to inflammatory changes occurring on HIV treatment.Item Blood pressure trajectories and the mediated effects of body mass index and HIV‐related inflammation in a mixed cohort of people with and without HIV in rural Uganda(The Journal of Clinical Hypertension, 2019) Okello, Samson; Kim, June‐Ho; Sentongo, Ruth N.; Tracy, Russell; Tsai, Alexander C.; Kakuhikire, Bernard; Siedner, Mark J.We sought to describe changes in blood pressure and estimate the effect of HIV on blood pressure (BP) over 4 years of observation in a cohort of 155 HIV‐infected adults (≥40 years) on antiretroviral therapy (ART) and 154 sex‐ and age‐quartilematched, population‐based, HIV‐uninfected controls for four years in rural Uganda, we compared changes in blood pressure (BP) by HIV serostatus and tested whether body mass index and inflammation (high‐sensitivity C‐reactive protein and interleukin‐ 6) and immune activation (sCD14 and sCD163) mediated the effects of HIV on BP using hierarchical multivariate and two‐stage parametric regression models. Overall HIV‐uninfected participants had higher mean BP than HIV‐infected counterparts (differences in trend P < 0.0001 for diastolic BP and P = 0.164 for systolic BP). After initial declines in BP in both groups between years 1 and 2, BP moderately increased in both groups through year 4, with greater change over time observed in the HIVuninfected group. Body mass index mediated 72% (95%CI 57, 97) of the association between HIV and systolic BP. We found a minimal mediating effect of sCD14 on the relationship between HIV and SBP (9%, 95% CI 5%, 21%), but found no association between other HIV‐related biomarkers. Over four years of observation, HIV‐infected people in rural Uganda have lower BP than HIV‐uninfected counterparts despite having higher levels of inflammation. BMI, rather than measures of HIV‐associated inflammation, explained a majority of the difference in BP observed.Item Gut Carriage of Antimicrobial Resistance Genes in Women Exposed to Small-Scale Poultry Farms in Rural Uganda: A Feasibility Study(PloS one, 2020) Weil, Ana A.; Debela, Meti D.; Muyanja, Daniel M.; Kakuhikire, Bernard; Baguma, Charles; Bangsberg, David R.; TsaiID, Alexander C.; Lai, Peggy S.Antibiotic use for livestock is presumed to be a contributor to the acquisition of antimicrobial resistance (AMR) genes in humans, yet studies do not capture AMR data before and after livestock introduction.We performed a feasibility study by recruiting a subset of women in a delayed-start randomized controlled trial of small-scale chicken farming to examine the prevalence of clinically-relevant AMR genes. Stool samples were obtained at baseline and one year post-randomization from five intervention women who received chickens at the start of the study, six control women who did not receive chickens until the end of the study, and from chickens provided to the control group at the end of the study. Stool was screened for 87 clinically significant AMR genes using a commercially available qPCR array (Qiagen).Chickens harbored 23 AMR genes from classes found in humans as well as additional vancomycin and β-lactamase resistance genes. AMR patterns between intervention and control women appeared more similar at baseline than one year post randomization (PERMANOVA R2 = 0.081, p = 0.61 at baseline, R2 = 0.186, p = 0.09 at 12 months) Women in the control group who had direct contact with the chickens sampled in the study had greater similarities in AMR gene patterns to chickens than those in the intervention group who did not have direct contact with chickens sampled (p = 0.01). However, at one year there was a trend towards increased similarity in AMR patterns between humans in both groups and the chickens sampled (p = 0.06).Studies designed to evaluate human AMR genes in the setting of animal exposure should account for high baseline AMR rates. Concomitant collection of animal, human, and environmental samples over time is recommended to determine the directionality and source of AMR genes.Item HIV infection, pulmonary tuberculosis and COPD in rural Uganda: A cross-sectional study(Lung, 2018) North, Crystal M.; Allen, Joseph G.; Okello, Samson; Sentongo, Ruth; Kakuhikire, Bernard; Ryan, Edward T.; Tsai, Alexander C.; Christiani, David C.; Siedner, Mark J.HIV is associated with chronic obstructive pulmonary disease (COPD) in high resource settings. Similar relationships are less understood in low resource settings. We aimed to estimate the association between HIV infection, tuberculosis and COPD in rural Uganda. Methods: The Uganda Non-Communicable Diseases and Aging Cohort study observes people 40 years and older living with HIV (PLWH) on antiretroviral therapy, and population-based HIV-uninfected controls in rural Uganda. Participants completed respiratory questionnaires and post-bronchodilator spirometry. Results: Among 269 participants with spirometry, median age was 52 (IQR 48–55), 48% (n=130) were ever-smokers, and few (3%, n=9) reported a history of COPD or asthma. All participants with prior tuberculosis (7%, n=18) were PLWH. Among 143 (53%) PLWH, median CD4 count was 477 cells/mm3 and 131 (92%) were virologically suppressed. FEV1 was lower among older individuals (−0.5 %pred/year, 95% CI 0.2–0.8, p<0.01) and those with a history of tuberculosis (−14.4 %pred, 95% CI −23.5 - −5.3, p < 0.01). COPD was diagnosed in 9 (4%) participants, eight of whom (89%) were PLWH, 6 of whom (67%) had a history of tuberculosis, and all of whom (100%) were men. Among 287 participants with complete symptom questionnaires, respiratory symptoms were more likely among women (AOR 3.9, 95% CI 2.0–7.7, p<0.001) and those in homes cooking with charcoal (AOR 3.2, 95% CI 1.4–7.4, p=0.008).Item Intimate Partner Violence and HIV Testing among Women in Rural South western Uganda(Journal of Clinical and Translational Science, 2021) Schember, Cassandra; Perkins, Jessica; Nyakato, Viola; Kakuhikire, Bernard; Kiconco, Allen; Namara, Betty; Brown, Lauren; Audet, Carolyn; Pettit, April; Bangsberg, David; Tsai, AlexanderThis research shows that physical intimate partner violence was associated with never testing for HIV while verbal intimate partner violence was associated with increased testing for HIV suggesting that HIV testing interventions should consider intimate partner violence prevention. OBJECTIVES/GOALS: HIV incidence is higher among women who experience intimate partner violence (IPV). However, few studies have assessed the association between HIV testing (regardless of the result) and the experience of IPV. Our objective was to assess the relationship between IPV and HIV testing among women from rural southwestern Uganda.Item Low population prevalence of atrial fibrillation in rural Uganda: A community-based cross-sectional study(International journal of cardiology, 2018) Muthalaly, Rahul G.; Koplan, Bruce A.; Albano, Alfred; North, Crystal; Campbell, Jeffrey I.; Kakuhikire, Bernard; Vořechovská, Dagmar; Kraemer, John D.; Tsai, Alexander C.; Siedner, Mark J.Atrial fibrillation (AF) is a major risk factor for stroke, which is the leading cause of cardiovascular mortality in sub-Saharan Africa. However, there is limited population-based epidemiological data on AF in sub-Saharan Africa. We sought to estimate the prevalence and correlates of AF in rural Uganda.We conducted a cross-sectional study using community health fairs in 2015 targeting eight villages in rural Uganda. Study participants completed a medical history, a clinical exam, blood collection, and 12‑lead electrocardiographic (ECG) screening. Of 1814 participants enrolled in a parent cohort study that includes 98% of adults residing in the geographic area, 856 attended a health fair and were included in this study. Our primary outcome was AF or atrial flutter. We modelled population prevalence of the outcome with inverse probability of treatment weighting using data collected from the full population.856 (47.2%) adults in the area attended a health fair and were included in the analysis. Health fair attendees were older (42 vs 34 years, P < 0.0001), in worse self-reported health (P < 0.0001) and more likely to be female (62% vs 49%, P < 0. 0001) compared with non-attendees. After applying weights, the estimated population mean age was 37.7 ± 14.9 years. 15% of the population was overweight or obese and 1.9% had left atrial enlargement on ECG. Despite this, the weighted estimate of AF was 0% (95%CI 0–0.54%).AF appears less prevalent in rural Uganda than in developed countries. The explanations for this finding may be genetic, environmental or related to survivorship bias.Item Lung function and atherosclerosis: a cross‑sectional study of multimorbidity in rural Uganda(BMC pulmonary medicine, 2022) Gilbert, Rebecca F.; Cichowitz, Cody; Bibangambah, Prossy; Kim, June‑Ho; Hemphill, Linda C.; Yang, Isabelle T.; Sentongo, Ruth N.; Kakuhikire, Bernard; Christiani, David C.; Tsai, Alexander C.; Okello, Samson; Siedner, Mark J.; North, Crystal M.Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality. In high-income settings, the presence of cardiovascular disease among people with COPD increases mortality and complicates longitudinal disease management. An estimated 26 million people are living with COPD in sub-Saharan Africa, where risk factors for co-occurring pulmonary and cardiovascular disease may differ from high-income settings but remain uncharacterized. As non-communicable diseases have become the leading cause of death in sub-Saharan Africa, defining multimorbidity in this setting is critical to inform the required scale-up of existing healthcare infrastructure. Methods: We measured lung function and carotid intima media thickness (cIMT) among participants in the UGANDAC Study. Study participants were over 40 years old and equally divided into people living with HIV (PLWH) and an age- and sex-similar, HIV-uninfected control population. We fit multivariable linear regression models to characterize the relationship between lung function (forced expiratory volume in one second, FEV1) and pre-clinical atherosclerosis (cIMT), and evaluated for effect modification by age, sex, smoking history, HIV, and socioeconomic status. Results: Of 265 participants, median age was 52 years, 125 (47%) were women, and 140 (53%) were PLWH. Most participants who met criteria for COPD were PLWH (13/17, 76%). Median cIMT was 0.67 mm (IQR: 0.60 to 0.74), which did not differ by HIV serostatus. In models adjusted for age, sex, socioeconomic status, smoking, and HIV, lower FEV1 was associated with increased cIMT (β = 0.006 per 200 mL FEV1 decrease; 95% CI 0.002 to 0.011, p = 0.01). There was no evidence that age, sex, HIV serostatus, smoking, or socioeconomic status modified the relationship between FEV1 and cIMT. Conclusions: Impaired lung function was associated with increased cIMT, a measure of pre-clinical atherosclerosis, among adults with and without HIV in rural Uganda. Future work should explore how co-occurring lung and cardiovascular disease might share risk factors and contribute to health outcomes in sub-Saharan Africa.Item Prevalence and correlates of chronic obstructive pulmonary disease and chronic respiratory symptoms in rural southwestern Uganda: a cross-sectional, population-based study(Journal of global health, 2019) North, Crystal M.; Kakuhikire, Bernard; Vořechovská, Dagmar; Kigozi, Simone Hausammann; McDonough, Amy Q.; Downey, Jordan; Christiani, David C.; Tsai, Alexander C.; Siedner, Mark J.The global burden of chronic obstructive pulmonary disease (COPD) disproportionately affects resource-limited settings such as sub-Saharan Africa (SSA), but population-based prevalence estimates in SSA are rare. We aimed to estimate the population prevalence of COPD and chronic respiratory symptoms in rural southwestern Uganda.Adults at least 18 years of age who participated in a population-wide census in rural southwestern Uganda completed respiratory questionnaires and lung function testing with bronchodilator challenge at health screening events in June 2015. We defined COPD as post-bronchodilator forced expiratory volume in one second to forced vital capacity ratio less than the lower limit of normal. We fit multivariable linear and log binomial regression models to estimate correlates of abnormal lung function and respiratory symptoms, respectively. We included inverse probability of sampling weights in models to facilitate population-level estimates.Forty-six percent of census participants (843/1814) completed respiratory questionnaires and spirometry, of which 565 (67%) met acceptability standards. COPD and respiratory symptom population prevalence were 2% (95% confidence interval (CI) = 1%-3%) and 30% (95% CI = 25%-36%), respectively. Respiratory symptoms were more prevalent and lung function was lower among women and ever-smokers (P < 0.05). HIV serostatus was associated with neither respiratory symptoms nor lung function.COPD population prevalence was low despite prevalent respiratory symptoms. This work adds to the growing body of literature depicting lower-than-expected COPD prevalence estimates in SSA and raises questions about whether the high respiratory symptom burden in rural southwestern Uganda represents underlying structural lung disease not identified by screening spirometry.Item Relative wealth, subjective social status, and their associations with depression: Cross-sectional, population-based study in rural Uganda(SSM-population health, 2019) Smith, Meghan L.; Kakuhikire, Bernard; Baguma, Charles; Rasmussen, Justin D.; Perkins, Jessica M.; Cooper-Vince, Christine; Venkataramanif, Atheendar S.; Ashaba, Scholastic; Bangsberg, David R.; Tsai, Alexander C.Depression is a leading cause of disability worldwide, and has been found to be a consistent correlate of socioeconomic status (SES). The relative deprivation hypothesis proposes that one mechanism linking SES to health involves social comparisons, suggesting that relative SES rather than absolute SES is of primary importance in determining health status. Using data from a whole-population sample of 1,620 participants residing in rural southwestern Uganda, we estimated the independent associations between objective and subjective relative wealth and probable depression, as measured by the depression subscale of the Hopkins Symptom Checklist (HSCLD). Objective relative wealth was measured by an asset index based on information about housing characteristics and household possessions, which was used to rank study participants into quintiles (within each village) of relative household asset wealth. Subjective relative wealth was measured by a single question asking participants to rate their wealth, on a 5-point Likert scale, relative to others in their village. Within the population, 460 study participants (28.4%) screened positive for probable depression. Using Poisson regression with cluster-robust error variance, we found that subjective relative wealth was associated with probable depression, adjusting for objective relative wealth and other covariates (adjusted relative risk [aRR] comparing lowest vs. highest level of subjective relative wealth = 1.90, 95% confidence interval [CI]: 1.18, 3.06). Objective relative wealth was not associated with probable depression (aRR comparing lowest vs. highest quintile of objective relative wealth = 1.09, 95% CI: 0.77, 1.55). These results suggest that, in this context, subjective relative wealth is a stronger correlate of mental health status compared with objective relative wealth. Our findings are potentially consistent with the relative deprivation hypothesis, but more research is needed to explain how relative differences in wealth are (accurately or inaccurately) perceived and to elucidate the implications of these perceptions for health outcomes.Item Reliability, Validity, and Factor Structure of the Hopkins Symptom Checklist-25: Population-Based Study of Persons Living with HIV in Rural Uganda(AIDS and Behavior, 2018) Ashaba, Scholastic; Kakuhikire, Bernard; Vořechovská, Dagmar; Perkins, Jessica M.; Cooper-Vince, Christine E.; Maling, Samuel; Bangsberg, David R.; Tsai, Alexander C.Depression and anxiety are highly comorbid among people living with HIV (PLHIV), but few instruments for screening or measurement have been validated for use in sub-Saharan Africa. The objective of this study was to determine the reliability, validity, and factor structure of the 25-item Hopkins Symptom Checklist (HSCL) in a population-based sample of PLHIV in rural Uganda. This study was nested within an ongoing population-based cohort of all residents living in Nyakabare Parish, Mbarara District, Uganda. All participants who identified as HIV-positive by self-report were included in this analysis. We performed parallel analysis on the scale items and estimated the internal consistency of the identified sub-scales using ordinal alpha. To assess construct validity we correlated the sub-scales with related constructs, including subjective well being (happiness), food insecurity, and health status. Of 1814 eligible adults in the population, 158 (8.7%) self-reported being HIV positive. The mean age was 41 years, and 68% were women. Mean HSCL-25 scores were higher among women compared with men (1.71 vs. 1.44; t = 3.6, P < 0.001). Parallel analysis revealed a three-factor structure that explained 83% of the variance: depression (7 items), anxiety (5 items), and somatic symptoms (7 items). The ordinal alpha statistics for the sub-scales ranged from 0.83 to 0.91. Depending on the sub-scale, between 27 and 41% of the sample met criteria for caseness. Strong evidence of construct validity was shown in the estimated correlations between sub-scale scores and happiness, food insecurity, and self-reported overall health. The HSCL-25 is a reliable and valid measure of mental health among PLHIV in rural Uganda. In cultural contexts where somatic complaints are commonly elicited when screening for symptoms of depression, it may be undesirable to exclude somatic items from depression symptom checklists administered to PLHIV.Item Treated HIV Infection and Progression of Carotid Atherosclerosis in Rural Uganda: A Prospective Observational Cohort Study(Journal of the American Heart Association, 2021) Siedner, Mark J.; Bibangambah, Prossy; Kim, June-Ho; Lankowski, Alexander; Chang, Jonathan L.; Yang, Isabelle T.; Kwon, Douglas S.; North, Crystal M.; Triant, Virginia A.; Longenecker, Christopher; Ghoshhajra, Brian; Peck, Robert N.; Sentongo, Ruth N.; Gilbert, Rebecca; Kakuhikire, Bernard; Boum II, Yap; Haberer, Jessica E.; Martin, Jeffrey N.; Tracy, Russell; Hunt, Peter W.; Bangsberg, David R.; Tsai, Alexander C.; Hemphill, Linda C.; Okello, SamsonAlthough ≈70% of the world’s population of people living with HIV reside in sub-Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. METHODS AND RESULTS: We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population-based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3–4, range 1–5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P=0.15). In multivariable models, increasing age, blood pressure, and non–high- density lipoprotein cholesterol were associated with greater cIMT (P<0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001–0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003–0.008 mm], HIV×time interaction P=0.25). CONCLUSIONS: In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub-Saharan Africa.