Browsing by Author "Kibuuka, Hannah"
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Item Assessing the impact of HIV support groups on antiretroviral therapy adherence and viral suppression in the African cohort study(BMC Infectious Diseases, 2021) Mbah, Prudence; Iroezindu, Michael; Esber, Allahna L.; Dear, Nicole; Reed, Domonique; Adamu, Yakubu; Kibuuka, Hannah; Maswai, Jonah; Bahemana, Emmanuel; Ake, Julie A.; Polyak, Christina S.Support groups for people living with HIV (PLWH) may improve HIV care adherence and outcomes. We assessed the impact of support group attendance on antiretroviral therapy (ART) adherence and viral suppression in four African countries. Methods: The ongoing African Cohort Study (AFRICOS) enrolls participants at 12 clinics in Kenya, Uganda, Tanzania, and Nigeria. Self-reported attendance of any support group meetings, self-reported ART adherence, and HIV RNA are assessed every 6 months. Logistic regression models with generalized estimating equations were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for support group attendance and other factors potentially associated with ART adherence and viral suppression. Results: From January 2013 to December 1, 2019, 1959 ART-experienced PLWH were enrolled and 320 (16.3%) reported any support group attendance prior to enrollment. Complete ART adherence, with no missed doses in the last 30 days, was reported by 87.8% while 92.4% had viral suppression <1000copies/mL across all available visits. There was no association between support group attendance and ART adherence in unadjusted (OR 1.01, 95% CI 0.99–1.03) or adjusted analyses (aOR 1.00, 95% CI 0.98–1.02). Compared to PLWH who did not report support group attendance, those who did had similar odds of viral suppression in unadjusted (OR 0.99, 95% CI 0.978–1.01) and adjusted analyses (aOR 0.99, 95% CI 0.97–1.01). Conclusion: Support group attendance was not associated with significantly improved ART adherence or viral suppression, although low support group uptake may have limited our ability to detect a statistically significant impact.Item 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, ChristofEarly 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).Item Clinical similarities and differences between two large HIV cohorts in the United States and Africa(Plos one, 2022) Monroe, Anne K.; Polyak, Christina S.; Castel, Amanda D.; Esber, Allahna L.; Maganga, Lucas; Kibuuka, Hannah; Kiweewa, Francis; Ake, Julie A.Washington, DC, and sub-Saharan Africa are both affected by generalized HIV epidemics. However, care for persons living with HIV (PLWH) and clinical outcomes may differ in these geographically and culturally diverse areas. We compared patient and clinical site characteristics among adult persons living with HIV (PLWH) enrolled in two longitudinal HIV cohort studies—the African Cohort Study (AFRICOS) and the DC Cohort. Methods The DC Cohort is a clinic-based city-wide longitudinal cohort comprised of PLWH attending 15 HIV clinics in Washington, DC. Patients’ socio-demographic characteristics, clinical evaluations, and laboratory data are retrospectively collected from electronic medical records and limited manual chart abstraction. AFRICOS is a prospective observational cohort of PLWH and uninfected volunteers attending 12 select HIV care and treatment facilities in Nigeria, Kenya, Uganda and Tanzania. AFRICOS study participants are a subset of clinic patients who complete protocol-specific visits every 6 months with history and physical examination, questionnaire administration, and blood/sputum collection for ascertainment of HIV outcomes and comorbidities, and neurocognitive and functional assessments. Among participants aged 18 years, we generated descriptive statistics for demographic and clinical characteristics at enrollment and follow up and compared them using bivariable analyses. Results The study sample included 2,774 AFRICOS and 8,420 DC Cohort participants who enrolled from January 2013 (AFRICOS)/January 2011 (DC Cohort) through March 2018. AFRICOS participants were significantly more likely to be women (58.8% vs 27.1%) and younger (83.3% vs 61.1% aged < 50 years old) and significantly less likely to be MSM (only 0.1% of AFRICOS population reported MSM risk factor) than DC Cohort. Similar rates of current viral suppression (about 75% of both samples), hypertension, hepatitis B coinfection and alcohol use were observed. However, AFRICOS participants had significantly higher rates of CD4<200 and tuberculosis and significantly lower rates of obesity, DM, hepatitis C coinfection and syphilis. Conclusions With similar viral suppression outcomes, but many differences between our cohorts noted, the combined sample provides unique opportunities to assess and compare HIV care and treatment outcomes in the U.S. and sub-Saharan Africa. Comparing these two cohorts may inform care and treatment practices and may pave the way for future pathophysiologic analyses.Item Contraceptive Use in Women Enrolled into Preventive HIV Vaccine Trials: Experience from a Phase I/II Trial in East Africa(PLoS ONE, 2009) Kibuuka, Hannah; Guwatudde, David; Kimutai, Robert; Maganga, Lucas; Maboko, Leonard; Watyema, Cecilia; Sawe, Fredrick; Shaffer, Douglas; Matsiko, Dickson; Millard, Monica; Michael, Nelson; Wabwire-Mangen, Fred; Robb, MerlinHIV vaccine trials generally require that pregnant women are excluded from participation, and contraceptive methods must be used to prevent pregnancy during the trial. However, access to quality services and misconceptions associated with contraceptive methods may impact on their effective use in developing countries. We describe the pattern of contraceptive use in a multi-site phase I/IIa HIV Vaccine trial in East Africa (Uganda, Kenya and Tanzania) and factors that may have influenced their use during the trial. Methods: Pregnancy prevention counseling was provided to female participants during informed consent process and at each study visit. Participants’ methods of contraception used were documented. Methods of contraceptives were provided on site. Pregnancy testing was done at designated visits during the trial. Obstacles to contraceptive use were identified and addressed at each visit. Results: Overall, 103 (31.8%) of a total of 324 enrolled volunteers were females. Female participants were generally young with a mean age of 29(67.2), married (49.5%) and had less than high school education (62.1%). Hormonal contraceptives were the most common method of contraception (58.3%) followed by condom use (22.3%). The distribution of methods of contraception among the three sites was similar except for more condom use and less abstinence in Uganda. The majority of women (85.4%) reported to contraceptive use prior to screening. The reasons for not using contraception included access to quality services, insufficient knowledge of certain methods, and misconceptions. Conclusion: Although hormonal contraceptives were frequently used by females participating in the vaccine trial, misconceptions and their incorrect use might have led to inconsistent use resulting in undesired pregnancies. The study underscores the need for an integrated approach to pregnancy prevention counseling during HIV vaccine trials.Item Epidemiology and Surveillance of Influenza Viruses in Uganda between 2008 and 2014(PLoS ONE, 2016) Wabwire-Mangen, Fred; Mimbe, Derrick E.; Erima, Bernard; Mworozi, Edison A.; Millard, Monica; Kibuuka, Hannah; Lukwago, Luswa; Bwogi, Josephine; Kiconco, Jocelyn; Tugume, Titus; Mulei, Sophia; Ikomera, Christine; Tsui, Sharon; Malinzi, Stephen; Kasasa, Simon; Coldren, Rodney; Byarugaba, Denis K.Influenza surveillance was conducted in Uganda from October 2008 to December 2014 to identify and understand the epidemiology of circulating influenza strains in out-patient clinic attendees with influenza-like illness and inform control strategies. Methodology Surveillance was conducted at five hospital-based sentinel sites. Nasopharyngeal and/or oropharyngeal samples, epidemiological and clinical data were collected from enrolled patients. Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to identify and subtype influenza strains. Data were double-entered into an Epi Info 3.5.3 database and exported to STATA 13.0 software for analysis. Results Of the 6,628 patient samples tested, influenza virus infection was detected in 10.4% (n = 687/ 6,628) of the specimens. Several trends were observed: influenza circulates throughout the year with two peaks; the major one from September to November and a minor one from March to June. The predominant strains of influenza varied over the years: Seasonal Influenza A(H3) virus was predominant from 2008 to 2009 and from 2012 to 2014; Influenza A (H1N1)pdm01 was dominant in 2010; and Influenza B virus was dominant in 2011. The peaks generally coincided with times of higher humidity, lower temperature, and higher rainfall. Conclusion Influenza circulated throughout the year in Uganda with two major peaks of outbreaks with similar strains circulating elsewhere in the region. Data on the circulating strains of influenza and its patterns of occurrence provided critical insights to informing the design and timing of influenza vaccines for influenza prevention in tropical regions of sub-Saharan Africa.Item 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, AllahnaSexually 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.Item Factors influencing estimates of HIV-1 infection timing using BEAST(PLOS Computational Biology, 2021) Dearlove, Bethany; Tovanabutra, Sodsai; Owen, Christopher L.; Kibuuka, Hannah; Maganga, Lucas; Michael, Nelson L.; Robb, Merlin L.; Rolland, MorganeWhile large datasets of HIV-1 sequences are increasingly being generated, many studies rely on a single gene or fragment of the genome and few comparative studies across genes have been done. We performed genome-based and gene-specific Bayesian phylogenetic analyses to investigate how certain factors impact estimates of the infection dates in an acute HIV-1 infection cohort, RV217. In this cohort, HIV-1 diagnosis corresponded to the first RNA positive test and occurred a median of four days after the last negative test, allowing us to compare timing estimates using BEAST to a narrow window of infection. We analyzed HIV-1 sequences sampled one week, one month and six months after HIV-1 diagnosis in 39 individuals. We found that shared diversity and temporal signal was limited in acute infection, and insufficient to allow timing inferences in the shortest HIV-1 genes, thus dated phylogenies were primarily analyzed for env, gag, pol and near full-length genomes. There was no one best-fitting model across participants and genes, though relaxed molecular clocks (73% of best-fitting models) and the Bayesian skyline (49%) tended to be favored. For infections with single founders, the infection date was estimated to be around one week pre-diagnosis for env (IQR: 3–9 days) and gag (IQR: 5–9 days), whilst the genome placed it at a median of 10 days (IQR: 4–19). Multiply-founded infections proved problematic to date. Our ability to compare timing inferences to precise estimates of HIV-1 infection (within a week) highlights that molecular dating methods can be applied to withinhost datasets from early infection. Nonetheless, our results also suggest caution when using uniform clock and population models or short genes with limited information content.Item Genetic analysis of influenza B viruses isolated in Uganda during the 2009–2010 seasons(Virology Journal, 2013) Byarugaba, Denis K.; Erima, Bernard; Millard, Monica; Kibuuka, Hannah; Lukwago, L.; Bwogi, Josephine; Mimbe, Derrick; Mworozi, Edison A.; Sharp, Bridget; Krauss, Scott; Webby, Richard J.; Webster, Robert G.; Martin, Samuel K.; Wabwire-Mangen, Fred; Ducatez, Mariette F.Influenza B viruses can cause morbidity and mortality in humans but due to the lack of an animal reservoir are not associated with pandemics. Because of this, there is relatively limited genetic sequences available for influenza B viruses, especially from developing countries. Complete genome analysis of one influenza B virus and several gene segments of other influenza B viruses isolated from Uganda from May 2009 through December 2010 was therefore undertaken in this study. Methods: Samples were collected from patients showing influenza like illness and screened for influenza A and B by PCR. Influenza B viruses were isolated on Madin-Darby Canine Kidney cells and selected isolates were subsequently sequenced and analyzed phylogenetically.Item Molecular dating and viral load growth rates suggested that the eclipse phase lasted about a week in HIV-1 infected adults in East Africa and Thailand(PLoS Pathog, 2020) Rolland, Morgane; Tovanabutra, Sodsai; Dearlove, Bethany; Li, Yifan; Kibuuka, Hannah; Maganga, Lucas; Michael, Nelson L.; Robb, Merlin L.Most HIV-1 infected individuals do not know their infection dates. Precise infection timing is crucial information for studies that document transmission networks or drug levels at infection. To improve infection timing, we used the prospective RV217 cohort where the window when plasma viremia becomes detectable is narrow: the last negative visit occurred a median of four days before the first detectable HIV-1 viremia with an RNA test, referred below as diagnosis. We sequenced 1,280 HIV-1 genomes from 39 participants at a median of 4, 32 and 170 days post-diagnosis. HIV-1 infections were dated by using sequencebased methods and a viral load regression method. Bayesian coalescent and viral load regression estimated that infections occurred a median of 6 days prior to diagnosis (IQR: 9–3 and 11–4 days prior, respectively). Poisson-Fitter, which analyzes the distribution of hamming distances among sequences, estimated a median of 7 days prior to diagnosis (IQR: 15–4 days) based on sequences sampled 4 days post-diagnosis, but it did not yield plausible results using sequences sampled at 32 days. Fourteen participants reported a high-risk exposure event at a median of 8 days prior to diagnosis (IQR: 12 to 6 days prior). These different methods concurred that HIV-1 infection occurred about a week before detectable viremia, corresponding to 20 days (IQR: 34–15 days) before peak viral load.Item Molecular Epidemiology of Influenza A/H3N2 Viruses Circulating in Uganda(PLoS ONE, 2011) Byarugaba, Denis K.; Ducatez, Mariette F.; Erima, Bernard; Mworozi, Edison A.; Millard, Monica; Kibuuka, Hannah; Lukwago, Luswa; Bwogi, Josephine; Kaira, Blanche B.; Mimbe, Derrick; Schnabel, David C.; Krauss, Scott; Darnell, Daniel; Webby, Richard J.; Webster, Robert G.; Wabwire-Mangen, FredThe increasing availability of complete influenza virus genomes is deepening our understanding of influenza evolutionary dynamics and facilitating the selection of vaccine strains. However, only one complete African influenza virus sequence is available in the public domain. Here we present a complete genome analysis of 59 influenza A/H3N2 viruses isolated from humans in Uganda during the 2008 and 2009 season. Isolates were recovered from hospital-based sentinel surveillance for influenza-like illnesses and their whole genome sequenced. The viruses circulating during these two seasons clearly differed from each other phylogenetically. They showed a slow evolution away from the 2009/10 recommended vaccine strain (A/ Brisbane/10/07), instead clustering with the 2010/11 recommended vaccine strain (A/Perth/16/09) in the A/Victoria/208/09 clade, as observed in other global regions. All of the isolates carried the adamantane resistance marker S31N in the M2 gene and carried several markers of enhanced transmission; as expected, none carried any marker of neuraminidase inhibitor resistance. The hemagglutinin gene of the 2009 isolates differed from that of the 2008 isolates in antigenic sites A, B, D, and to a lesser extent, C and E indicating evidence of an early phylogenetic shift from the 2008 to 2009 viruses. The internal genes of the 2009 isolates were similar to those of one 2008 isolate, A/Uganda/MUWRP-050/2008. Another 2008 isolate had a truncated PB1-F2 protein. Whole genome sequencing can enhance surveillance of future seasonal changes in the viral genome which is crucial to ensure that selected vaccine strains are protective against the strains circulating in Eastern Africa. This data provides an important baseline for this surveillance. Overall the influenza virus activity in Uganda appears to mirror that observed in other regions of the southern hemisphere.Item Optimizing Highly Infectious Disease Isolation Unit Management: Experiences From the Infectious Diseases Isolation and Research Unit, Fort Portal, Uganda(Disaster Medicine and Public Health Preparedness, 2021) Alum, Susan; Asiimwe, Moses; Kanyomozi, Gerald; Nalikka, Jacqueline; Okwaro, Peace; Migisha, Isabella; Muhindo, Brenda; Wailagala, Abdullah; Okello, Stephen; Blair, Paul; Waitt, Peter; Bhadelia, Nahid; Ayebare, Rodgers; Kwiecien, Antonia; Saunders, David; Lamorde, Mohammed; Kibuuka, Hannah; Clark, DanielleInfectious disease outbreaks on the scale of the current coronavirus disease 2019 (COVID-19) pandemic are a new phenomenon in many parts of the world. Many isolation unit designs with corresponding workflow dynamics and personal protective equipment postures have been proposed for each emerging disease at the health facility level, depending on the mode of transmission. However, personnel and resource management at the isolation units for a resilient response will vary by human resource capacity, reporting requirements, and practice setting. This study describes an approach to isolation unit management at a rural Uganda Hospital and shares lessons from the Uganda experience for isolation unit managers in low- and middle-income settings.Item Perceived satisfaction with HIV care and its association with adherence to antiretroviral therapy and viral suppression in the African Cohort Study(AIDS research and therapy, 2021) Somi, Nancy; Dear, Nicole; Reed, Domonique; Parikh, Ajay; Lwilla, Anange; Bahemana, Emmanuel; Khamadi, Samoel; Iroezindu, Michael; Kibuuka, Hannah; Maswai, Jonah; Crowell, Trevor A.; Owuoth, John; Maganga, Lucas; Polyak, Christina; Ake, Julie; Esber, AllahnaIncreased availability of HIV care over the past decade has dramatically reduced morbidity and mortality among people living with HIV (PLWH) in sub-Saharan Africa. However, perceived and experienced barriers to care, including dissatisfaction with services, may impact adherence and viral suppression. We examined the associations between satisfaction with HIV care and antiretroviral therapy (ART) adherence and viral load suppression. Methods: The African Cohort Study (AFRICOS) is a prospective observational study conducted at PEPFAR-supported clinics in four African countries. At enrollment and twice-yearly study visits, participants received a clinical assessment and a socio-behavioral questionnaire was administered. Participants were classified as dissatisfied with care if they reported dissatisfaction with any of the following: waiting time, health care worker skills, health care worker attitudes, quality of clinic building, or overall quality of care received. Robust Poisson regression was used to estimate prevalence ratios and 95% confidence intervals (CIs) for associations between satisfaction with care and ART adherence and between satisfaction with care and viral suppression (viral load < 1000 copies/mL). Results: As of 1 March 2020, 2928 PLWH were enrolled and 2311 had a year of follow-up visits. At the first annual follow-up visit, 2309 participants responded to questions regarding satisfaction with quality of care, and 2069 (89.6%) reported satisfaction with care. Dissatisfaction with waiting time was reported by 177 (7.6%), building quality by 59 (2.6%), overall quality of care by 18 (0.8%), health care worker attitudes by 16 (0.7%), and health care worker skills by 15 (0.7%). After adjusting for age and site, there was no significant difference in viral suppression between those who were satisfied with care and those who were dissatisfied (aPR: 1.03, 95% CI 0.97–1.09). Satisfaction with HIV care was moderately associated with ART adherence among AFRICOS participants (aPR: 1.09; 95% CI 1.00–1.16). Conclusions: While patient satisfaction in AFRICOS was high and the association between perceived quality of care and adherence to ART was marginal, we did identify potential target areas for HIV care improvement, including reducing clinic waiting times.Item Poor biosecurity in live bird markets in Uganda: A potential risk for highly pathogenic avian influenza disease outbreak in poultry and spread to humans(Avian Diseases, 2014) Kirunda, Halid; Kibuuka, Hannah; Byaruhanga, Achilles; Mworozi, Edison; Bwogi, Josephine; Lukwago, Luswa,; Millard, Millard; Wabwire-Mangen, Fred; Byarugaba, Denis K.Live bird markets (LBMs) are essential for marketing of poultry, but can be a hub for the rapid spread of diseases including avian influenza (AI). We assessed the status of biosecurity in 108 LBMs in 37 districts of Uganda. In all LBMs, carcasses were disposed of in the open and birds were introduced in the markets without initial quarantine. A high proportion of markets lacked a dedicated site for unloading of birds (86.1%) and a programme for disinfection (99.1%), had dirty feed/water troughs (93.5%), were accessed by stray animals (97.2%), and had sick and healthy birds (96.3%) or different bird species (86.1%) sold together. Differences in practices occurred among geographical regions and market location. Birds were more likely to be slaughtered in the open in urban compared to rural LBMs (OR=14.6, 95% CI: 1.50 - 142), while selling of un-caged birds was less likely in central compared to western region (OR=0.2, 95% CI: 0.04 - 0.17). Different poultry species confined in the same cage were more likely to be sold in urban (OR=22, 95% CI: 1.14 - 435) compared to rural markets. We conclude that LBMs in Uganda are a potential risk for spread of AI to poultry and humans.Item Pre-positioned Outbreak Research: The Joint Medical Emerging Diseases Intervention Clinical Capability Experience in Uganda(Health security, 2020) Martins, Karen A.; Ayebare, Rodgers R.; Bhadelia, Nahid; Kiweewa, Francis; Waitt, Peter; Mimbe, Derrick; Okello, Stephen; Naluyima, Prossy; Brett-Major, David M.; Lawler, James V.; Millard, Monica; Walwema, Richard; Cardile, Anthony P.; Ritchie, Chi; Kwiecien, Antonia; Badu, Helen; Espinosa, Benjamin J.; Beckett, Charmagne; Bavari, Sina; Zaman, Saima; Christopher, George; Clark, Danielle V.; Lamorde, Mohammed; Kibuuka, HannahThe West Africa Ebola virus disease outbreak of 2014-2016 demonstrated that responses to viral hemorrhagic fever epidemics must go beyond emergency stopgap measures and should incorporate high-quality medical care and clinical research. Optimal patient management is essential to improving outcomes, and it must be implemented regardless of geographical location or patient socioeconomic status. Coupling clinical research with improved care has a significant added benefit: Improved data quality and management can guide the development of more effective supportive care algorithms and can support regulatory approvals of investigational medical countermeasures (MCMs), which can alter the cycle of emergency response to reemerging pathogens. However, executing clinical research during outbreaks of high-consequence pathogens is complicated and comes with ethical and research regulatory challenges. Aggressive care and excellent quality control must be balanced by the requirements of an appropriate infection prevention and control posture for healthcare workers and by overcoming the resource limitations inherent in many outbreak settings. The Joint Mobile Emerging Disease Intervention Clinical Capability was established in 2015 to develop a high-quality clinical trial capability in Uganda to support rigorous evaluation of MCMs targeting high-consequence pathogens like Ebola virus. This capability assembles clinicians, laboratorians, clinical researchers, logisticians, and regulatory professionals trained in infection prevention and control and in good clinical and good clinical laboratory practices. The resulting team is prepared to provide high-quality medical care and clinical research during high-consequence outbreaks.Item 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.Item The pregnancy factor: the prevalence of depression among women living with HIV enrolled in the African Cohort Study (AFRICOS) by pregnancy status(Archives of Women's Mental Health, 2021) Jones, Milissa U.; Esber, Allahna L.; Dear, Nicole; Bahemana, Emmanuel; Kibuuka, Hannah; Iroezindu, Michael; Maswai, Jonah; Owuoth, John; Polyak, Christina S.; Ake, Julie A.; Crowell, Trevor A.; Hickey, Patrick W.Among Sub-Saharan African women living with HIV (WLWH), pregnancy creates unique stressors that may cause depression. We describe the prevalence of depression among WLWHenrolled in the African Cohort Study (AFRICOS) by pregnancy status and describe factors associated with depression. WLWH < 45 years of age underwent six-monthly visits with depression diagnosed using the Center for Epidemiological Studies-Depression scale. Visits were categorized as “pregnant;” “postpartum” (the first visit made after the last pregnancy visit), and “non-pregnant.” The prevalence of depression was calculated for each visit type and compared using prevalence odds ratios (POR) with 95% confidence intervals (CI). Logistic regression with generalized estimating equations was used to evaluate sociodemographic factors associated with depression. From January 2013 toMarch 1, 2020, 1333 WLWH were enrolled, and 214 had pregnancies during follow-up. As compared to the prevalence of depression during “non-pregnant” visits (9.1%), depression was less common at “pregnant” (6.3%; POR = 0.68 [CI: 0.42, 1.09]) and “postpartum” (3.4%; POR = 0.36 [CI: 0.17, 0.76]) visits. When controlling for other factors, the visit category was not independently associated with depression. Visit number, study site, employment status, and food security were independently associated with decreased odds of depression. We observed a lower prevalence of depression during pregnancy and the postpartum period than has been previously described amongWLWH during similar time points.We observed protective factors against depression which highlight the impact that holistic and consistent health care at HIV-centered clinics may have on the well-being ofWLWH in AFRICOS.Item Prevalence and predictors of food insecurity among people living with and without HIV in the African Cohort Study(Public Health Nutrition, 2022) Onyenakie, Cecilia C.; Nnakwe, Raphael U.; Dear, Nicole; Esber, Allahna; Bahemana, Emmanuel; Kibuuka, Hannah; Maswai, Jonah; Owuoth, John; Crowell, Trevor A.; Polyak, Christina S.; Ake, Julie A.; Iroezindu, MichaelWe determined the prevalence and identified predictors of food insecurity in four African countries. Design: Cross-sectional analyses at study enrolment. Setting: From January 2013 to March 2020, people living with HIV (PLWH) and without HIV were enrolled at twelve clinics in Kenya, Uganda, Tanzania and Nigeria. Participants: Participants reporting not having enough food to eat over the past 12 months or receiving <3 meals/d were defined as food insecure. Robust Poisson regression models were used to estimate unadjusted and adjusted prevalence ratios (aPR) and 95 % CI for predictors of food insecurity among all participants and separately among PLWH. Results: 1694/3496 participants (48·5 %) reported food insecurity at enrolment, with no difference by HIV status. Food insecurity was more common among older participants (50þ v. 18–24 years aPR 1·35, 95 % CI 1·15, 1·59). Having 2–5 (aPR 1·14, 95 % CI 1·01, 1·30) or >5 dependents (aPR 1·17, 95 % CI 1·02, 1·35), and residing in Kisumu West, Kenya (aPR 1·63, 95 % CI 1·42, 1·87) or Nigeria (aPR 1·20, 95 % CI 1·01, 1·41) was associated with food insecurity. Residing in Tanzania (aPR 0·65, 95 % CI 0·53, 0·80) and increasing education (secondary/above education v. none/ some primary education aPR 0·73, 95 % CI 0·66, 0·81) was protective against food insecurity. Antiretroviral therapy (ART)-experienced PLWH were more likely to be food secure irrespective of viral load. Conclusion: Food insecurity was highly prevalent in our cohort though not significantly associated with HIV. Policies aimed at promoting education, elderly care, ART access in PLWH and financial independence could potentially improve food security in Africa.Item Prevalence and risk factors associated with HIV and syphilis co‑infection in the African Cohort Study: a cross‑sectional study(BMC Infectious Diseases, 2021) Gilbert, Laura; Dear, Nicole; Esber, Allahna; Iroezindu, Michael; Bahemana, Emmanuel; Kibuuka, Hannah; Owuoth, John; Maswai, Jonah; Crowell, Trevor A.; Polyak, Christina S.; Ake, Julie A.Each year, 5.6 million new syphilis cases are diagnosed globally. Guidelines for people living with HIV (PLWH) in low-income countries (LIC) recommend STI testing for symptomatic persons and those newly diagnosed with HIV; routine STI testing is less clear. Here we provide updated syphilis prevalence and identify co-infection risk factors in PLWH in the African Cohort Study (AFRICOS) to understand these rates as they relate to syndromic treatment. Methods: AFRICOS is a study enrolling PLWH and HIV-uninfected individuals in four African countries. Participant study enrollment information was used to determine syphilis prevalence and co-infection risk factors. Inclusion criteria consisted of adults 18 years or older receiving care at a participating clinic as a long-term resident who consented to data and specimen collection. Exclusion criteria consisted of pregnancy and/or imprisonment. Screen-positive syphilis was defined as a reactive rapid plasma regain (RPR) upon study enrollment whereas confirmed syphilis included a reactive RPR followed by reactive treponemal test. Multivariate analyses was performed to determine HIV and syphilis co-infection risk factors. Results: Between 2013 and March 1, 2020, 2939 PLWH enrolled and 2818 were included for analysis. Screen-positive and confirmed syphilis prevalence were 5.3% (151/2818) and 3.1% (87/2818), respectively. When the analysis was restricted to PLWH with an RPR titer of greater than, or equal to, 1:8, 11/87 (12.6%) participants were included. No PLWH and confirmed syphilis had documented genital ulcers. In the multivariate model, participants with confirmed syphilis co-infection were more likely to have none or some primary education [aOR 3.29 (1.60, 6.74)] and consume alcohol [aOR 1.87 (1.16, 3.03)] compared to those without syphilis. Antiretroviral therapy (ART) with suppressed viral load (VL) was protective in the unadjusted model but not adjusted multivariate model. Conclusions: Our findings show that syphilis rates in sub-Saharan Africa remain elevated where diagnosis remains challenging, and that both lower education level and alcohol consumption are significantly associated with HIV/syphilis co-infection in AFRICOS. Based on our analysis, current STI guidelines targeting testing for African individuals with either new HIV diagnosis or syndromic symptoms may be inadequate, highlighting the need for increased testing and treatment strategies in resource-limited settings.Item Prevalence of influenza A viruses in livestock and free-living waterfowl in Uganda(BMC Veterinary Research, 2014) Kirunda, Halid; Erima, Bernard; Tumushabe, Agnes; Kiconco, Jocelyn; Tugume, Titus; Mulei, Sophia; Mimbe, Derrick; Mworozi, Edison; Bwogi, Josephine; Luswa, Lukwago; Kibuuka, Hannah; Millard, Monica; Byaruhanga, Achilles; Ducatez, Mariette F.; Krauss, Scott; Webby, Richard J.; Webster, Robert G.; Wurapa, Kofi; Byarugaba, Denis K.; Wabwire-Mangen, FredAvian influenza viruses may cause severe disease in a variety of domestic animal species worldwide, with high mortality in chickens and turkeys. To reduce the information gap about prevalence of these viruses in animals in Uganda, this study was undertaken. Results: Influenza A virus prevalence by RT-PCR was 1.1% (45/4,052) while sero prevalence by ELISA was 0.8% (24/2,970). Virus prevalence was highest in domestic ducks (2.7%, 17/629) and turkeys (2.6%, 2/76), followed by free-living waterfowl (1.3%, 12/929) and swine (1.4%, 7/511). A lower proportion of chicken samples (0.4%, 7/1,865) tested positive. No influenza A virus was isolated. A seasonal prevalence of these viruses in waterfowl was 0.7% (4/561) for the dry and 2.2% (8/368) for the wet season. In poultry, prevalence was 0.2% (2/863) for the dry and 1.4% (24/1,713) for the wet season, while that of swine was 0.0% (0/159) and 2.0% (7/352) in the two seasons, respectively. Of the 45 RT-PCR positive samples, 13 (28.9%) of them were H5 but none was H7. The 19 swine sera positive for influenza antibodies by ELISA were positive for H1 antibodies by HAI assay, but the subtype(s) of ELISA positive poultry sera could not be determined. Antibodies in the poultry sera could have been those against subtypes not included in the HAI test panel. Conclusions: The study has demonstrated occurrence of influenza A viruses in animals in Uganda. The results suggest that increase in volumes of migratory waterfowl in the country could be associated with increased prevalence of these viruses in free-living waterfowl and poultry.Item Relatively Low HIV Infection Rates in Rural Uganda, but with High Potential for a Rise: A Cohort Study in Kayunga District, Uganda(PLoS ONE, 2009) Guwatudde, David; Wabwire-Mangen, Fred; Eller, Leigh Anne; Eller, Michael; McCutchan, Francine; Kibuuka, Hannah; Millard, Monica; Sewankambo, Nelson; Serwadda, David; Michael, Nelson; Robb, MerlinFew studies have been conducted in Uganda to identify and quantify the determinants of HIV-1 infection. We report results from a community-based cohort study, whose primary objectives were to determine HIV-1 prevalence, incidence, and determinants of these infections, among other objectives. Methodology: Consenting volunteers from the rural district of Kayunga in Uganda aged 15–49 years were enrolled between March and July 2006. Participants were evaluated every six months. A questionnaire that collected information on behavioral and other HIV-1 risk factors was administered, and a blood sample obtained for laboratory analysis at each study visit. Principal Findings: HIV-1 prevalence among the 2025 participants was 9.9% (95% CI = 8.6%–11.2%). By the end of 12 months of follow-up, 1689.7 person-years had been accumulated, with a median follow-up time of 11.97 months. Thirteen HIV-1 incident cases were detected giving an annual HIV-1 incidence of 0.77% (95% CI = 0.35–1.19). Prevalence of HSV-2 infection was 57% and was strongly associated with prevalent HIV-1 infection (adjusted Odds Ratio = 3.9, 95% CI = 2.50–6.17); as well as incident HIV-1 infection (adjusted Rate Ratio (RR) = 8.7, 95% CI = 1.11–67.2). The single most important behavioral characteristic associated with incident HIV infection was the number of times in the past 6 months, a participant had sex with person(s) they suspected/knew were having sex with others; attaining statistical significance at 10 times and higher (adjusted RR = 6.3, 95% CI = 1.73–23.1). By the end of 12 months of follow-up, 259 participants (13%) were lost to follow-up, 13 (0.6%) had died, and 2 (0.1%) had withdrawn consent. Conclusions: Despite relatively low HIV-1 incidence observed in this community, prevalence remains relatively high. In the presence of high prevalence of HSV-2 infection and the behavioral characteristic of having sex with more than one partner, there is potential for increase in HIV-1 incidence.