Browsing by Author "Semwogerere, Michael"

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    Assessment of tuberculosis disease activity in people infected with Mycobacterium tuberculosis and living with HIV: A longitudinal cohort study
    (EClinicalMedicine, 2022) Kroidl, Inge; Ahmed, Mohamed I.M.; Horn, Sacha; Kibuuka, Hannah; Semwogerere, Michael; Mwesigwa, Betty; Naluyima, Prossy; Kasumba, Joy Mary; Maswai, Jonah; Geldmacher, Christof
    Early detection of asymptomatic incipient tuberculosis (TB) could improve clinical outcomes and reduce the spread of Mycobacterium tuberculosis (MTB) infection, particularly in HIV endemic settings. This study assessed TB disease activity over 5 years in people living with HIV co-infected with MTB using a surrogate biomarker. Methods Between Jan 1, 2013 and Aug 31, 2018, 2014 people living with HIV were screened annually for active TB using the Xpert MTB/RIF diagnostic assay in 11 clinics in Kenya, Tanzania, Uganda, and Nigeria. Longitudinal blood mononuclear cell samples from 46 selected patients with active and recurrent tuberculosis, latent infection, or incipient TB were further analysed for MTB-specific T-cell activation (defined by CD38 expression) as a well-defined surrogate marker for TB disease covering a total of 1758 person-months. Findings MTB-specific CD4 T-cell activation differentiated active, Xpert MTB/RIF positive TB from latent TB with a sensitivity and specificity of 86% and was reduced upon TB treatment initiation. Activated MTB-specific T cells were present in 63% and 23% of incipient TB cases 6 and 12 months before diagnosis of active disease, respectively. Transient increases of MTB-specific T cell activation were also observed in individuals with latent infection, while persistent activation was a hallmark of recurrent TB after the end of treatment. Interpretation In most cases, progression to active TB disease started 6−12 months before diagnosis by clinical symptoms and sputum occurrence of bacilli. Blood biomarkers could facilitate early detection of incipient TB, improve clinical outcomes, and reduce the transmission of MTB. Funding This work was supported by the President’s Emergency Plan for AIDS Relief via a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense [W81XWH-11-2-0174, W81XWH-18-2-0040] and by the Bundesministerium f€ur Bildung und Forschung (BmBF) through funding of the Deutsches Zentrum f€ur Infektionsforschung (DZIF, TTU-TB personalized medicine TTU 02_813).
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    Factors associated with sexually transmitted infections among care-seeking adults in the African Cohort Study
    (BMC public health, 2021) Semwogerere, Michael; Dear, Nicole; Tunnage, Joshua; Reed, Domonique; Kibuuka, Hannah; Kiweewa, Francis; Iroezindu, Michael; Bahemana, Emmanuel; Maswai, Jonah; Owuoth, John; Crowell, Trevor A.; Ake, Julie A.; Polyak, Christina S.; Esber, Allahna
    Sexually transmitted infections (STIs) are a major cause of morbidity. Understanding drivers of transmission can inform effective prevention programs. We describe STI prevalence and identify factors associated with STIs in four African countries. Methods: The African Cohort Study is an ongoing, prospective cohort in Kenya, Nigeria, Tanzania and Uganda. At enrollment, a physical exam was conducted and STI diagnosis made by a clinician using a syndromic management approach. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for factors associated with an STI diagnosis. Results: As of June 2020, 3544 participants were enrolled. STI prevalence was 7.7% and did not differ by HIV status (p = 0.30). Prevalence differed by syndrome (3.5% vaginal discharge, 1.5% genital ulcer, 2.1% lower abdominal pain, 0.2% inguinal bubo). The odds of having an STI were higher at all sites compared to Kisumu West, Kenya, and among those with a primary level education or below compared to those with secondary or higher (aOR: 1.77; 95% CI: 1.32–2.38). The odds of an STI diagnosis was higher among participants 18–29 years (aOR: 2.29; 95% CI: 1.35– 3.87), females (aOR: 2.64; 95% CI: 1.94–3.59), and those with depression (aOR: 1.78; 95% CI: 1.32–2.38). Among PLWH, similar factors were independently associated with an STI diagnosis. Viral suppression was protective against STIs (aOR: 2.05; 95% CI: 1.32–3.20). Conclusions: Prevalence of STIs varied by site with young people and females most at risk for STIs. Mental health is a potential target area for intervention.
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    Predictors of All-Cause Mortality Among People With Human Immunodeficiency Virus (HIV) in a Prospective Cohort Study in East Africa and Nigeria
    (Clinical Infectious Diseases, 2022) Kibuuka, Hannah; Musingye, Ezra; Mwesigwa, Betty; Semwogerere, Michael; Iroezindu, Michael; Bahemana, Emmanuel; Maswai, Jonah; Owuoth, John; Esber, Allahna; Dear, Nicole; Crowell, Trevor A.; Polyak, Christina S.; Ake, Julie A.
    Introduction of antiretroviral therapy (ART) has been associated with a decline in human immunodeficiency virus (HIV)-related mortality, although HIV remains a leading cause of death in sub-Saharan Africa. We describe all-cause mortality and its predictors in people living with HIV (PLWH) in the African Cohort Study (AFRICOS). Methods. AFRICOS enrolls participants with or without HIV at 12 sites in Kenya, Uganda, Tanzania, and Nigeria. Evaluations every 6 months include sociobehavioral questionnaires, medical history, physical examination, and laboratory tests. Mortality data are collected from medical records and survivor interviews. Multivariable Cox proportional hazards models were used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for factors associated with mortality. Results. From 2013 through 2020, 2724 PLWH completed at least 1 follow-up visit or experienced death. Of these 58.4% were females, 25.8% were aged ≥ 50 years, and 98.3% were ART-experienced. We observed 11.42 deaths per 1000 person-years (95% CI: 9.53–13.68) with causes ascertained in 54% of participants. Deaths were caused by malignancy (28.1%), infections (29.7%), and other non-HIV related conditions. Predictors of mortality included CD4 ≤ 350 cells/μL (aHR 2.01 [95% CI: 1.31–3.08]), a log10copies/mL increase of viral load (aHR 1.36 [95% CI: 1.22–1.51]), recent fever (aHR 1.85[95% CI: 1.22–2.81]), body mass index < 18.5 kg/m2 (aHR 2.20 [95% CI: 1.44–3.38]), clinical depression (aHR 2.42 [95% CI: 1.40–4.18]), World Health Organization (WHO) stage III (aHR 2.18 [95% CI: 1.31–3.61]), a g/dL increase in hemoglobin (aHR 0.79 [95% CI: .72–.85]), and every year on ART (aHR 0.67 [95% CI: .56–.81]). Conclusions. The mortality rate was low in this cohort of mostly virally suppressed PLWH. Patterns of deaths and identified predictors suggest multiple targets for interventions to reduce mortality.