Browsing by Author "Kiwanuka, Noah"
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Item Accuracy and reliability of a wireless vital signs monitor for hospitalized patients in a low-resource setting(Digital Health, 2022) Nantume, Assumpta; Kiwanuka, Noah; Muyinda, Asad; Cauvel, Teresa; Shah, SonaThe purpose of this study was to evaluate the accuracy and reliability of neoGuard in comparison to a conventional bedside monitor on patients in a low-resource clinical setting. This was a single-arm methods comparison study involving the use of a wearable vital signs monitor (neoGuardTM) versus a conventional bedside monitor (Edan iM8). The study was conducted at Jinja Regional Referral Hospital, a tertiary care hospital situated in Eastern Uganda. Participants: Thirty patients (10 male, 20 female) were enrolled from the adult recovery ward at JRRH. Participants were eligible for the study if they were at least 18 years of age, had 2 sets of normal vital sign measurements obtained 1 h apart, and were able and willing to provide informed consent. Main Outcome and Measures: The primary outcome measures were (i) bias (mean deviation) and (ii) limits of agreement [95% CI]. Bland-Altman plots were generated to illustrate the level of agreement between the neoGuardTM technology and the Edan iM8 monitor. Bland-Altman analysis was performed for 24 participants; datasets from six participants were excluded due to missing or invalid measurements. Findings showed a moderate level of agreement for measurement of SpO2, PR, and RR, with >80% of subject means falling within the predefined acceptability limits. However, there was also notable variation in accuracy between subjects, with large standard deviations observed for measurement of all four parameters. While the level of agreement for measurement of temperature was low, this is partly explained by limitations in the comparison method.Item Acute Hypoxaemic Respiratory Failure In A Low-Income Country: A Prospective Observational Study Of Hospital Prevalence And Mortality(BMJ Open Respiratory Research, 2020) Kwizera, Arthur; Nakibuuka, Jane; Nakiyingi, Lydia; Sendagire, Cornelius; Tumukunde, Janat; Katabira, Catherine; Ssenyonga, Ronald; Kiwanuka, Noah; Kateete, David Patrick; Joloba, Moses; Kabatoro, Daphne; Atwine, Diana; Summers, CharlotteLimited data exist on the epidemiology of acute hypoxaemic respiratory failure (AHRF) in low-income countries (LICs). We sought to determine the prevalence of AHRF in critically ill adult patients admitted to a Ugandan tertiary referral hospital; determine clinical and treatment characteristics as well as assess factors associated with mortality.We conducted a prospective observational study at the Mulago National Referral and Teaching Hospital in Uganda. Critically ill adults who were hospitalised at the emergency department and met the criteria for AHRF (acute shortness of breath for less than a week) were enrolled and followed up for 90 days. Multivariable analyses were conducted to determine the risk factors for death.A total of 7300 patients was screened. Of these, 327 (4.5%) presented with AHRF. The majority (60 %) was male and the median age was 38 years (IQR 27–52). The mean plethysmographic oxygen saturation (SpO2) was 77.6% (SD 12.7); mean SpO2/FiO2 ratio 194 (SD 32) and the mean Lung Injury Prediction Score (LIPS) 6.7 (SD 0.8). Pneumonia (80%) was the most common diagnosis. Only 6% of the patients received mechanical ventilatory support. In-hospital mortality was 77% with an average length of hospital stay of 9.2 days (SD 7). At 90 days after enrolment, the mortality increased to 85%. Factors associated with mortality were severity of hypoxaemia (risk ratio (RR) 1.29 (95% CI 1.15 to 1.54), p=0.01); a high LIPS (RR 1.79 (95% CI 1.79 1.14 to 2.83), p=0.01); thrombocytopenia (RR 1.23 (95% CI 1.11 to 1.38), p=0.01); anaemia (RR 1.15 (95% CI 1.01 to 1.31), p=0.03) ; HIV co-infection (RR 0.84 (95% CI 0.72 to 0.97), p=0.019) and male gender (RR 1.15 (95% CI 1.01 to 1.31) p=0.04).The prevalence of AHRF among emergency department patients in a tertiary hospital in an LIC was low but was associated with very high mortality. Pneumonia was the most common cause of AHRF. Mortality was associated with higher severity of hypoxaemia, high LIPS, anaemia, HIV co-infection, thrombocytopenia and being male.Item Adipose-derived stromal vascular fraction (SVF) in scar treatment: a systematic review protocol(American Journal of Stem Cells, 2022) Mbiine, Ronald; Wayengera, Misaki; Ocan, Moses; Kiwanuka, Noah; Munabi, Ian; Muwonge, Haruna; Lekuya, Hervé Monka; Kawooya2, Ismael Cephas Nakanwagi3,4, Alison Annet Kinengyere; Joloba, Moses; Galukande, MosesAutologous adipose-derived stromal vascular fraction (SVF) is an emerging therapy that is being pioneered as a potential treatment for keloids and hypertrophic scars. Up to this point, there isn’t a cure for keloids and hypertrophic scars yet they comprise the commonest benign skin disorders. Despite published studies reporting potential therapeutic benefits of SVF, their use and efficacy on scar improvement are not clearly described. The aim of this review is to describe the clinical practice involved in harvesting, processing, utilization of SVF, and associated efficacy in scar treatment. Methods: We shall include published clinical articles evaluating the efficacy of SVF on improving scar characteristics and assessment scores among adults with keloids or hypertrophic scars. Article search of Medline/PubMed, Cochrane Library and Embase using Mesh terms of “scars” and “stromal vascular fraction” combined with the Boolean operators (“AND”, “OR”) will be performed by two independent researchers following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. The primary outcome measure will be the mean difference in the Scar characteristics including Scar assessment scores, scar thickness among others. Data synthesis: Descriptive data synthesis and mean differences between treatment arms will be calculated for the primary outcome of the scar assessment scores. In case more than three studies provide consistent characteristics of the scar assessment scores, a meta-analysis will be conducted. Discussion: Evidence obtained from the systematic review will form the foundation upon which further clinical trials research will be conducted in evaluating the efficacy of autologous adipose-derived stromal vascular fraction in keloid and hypertrophic scar. The systematic review has been submitted to the PROSPERO database and is currently under review.Item Age of male circumcision and risk of prevalent HIV infection in rural Uganda(Aids, 1999) Kelly, Robert; Kiwanuka, Noah; Wawer, Maria J.; Serwadda, David; Sewankambo, Nelson; Wabwire-Mangen, Fred; Li, Chuanjun; Konde-Lule, Joseph K.; Lutalo, Tom; Makumbi, Fred; Gray, Ronald H.Epidemiological evidence suggests that male circumcision may reduce the risk of sexually transmitted diseases (STD) and possibly HIV infection. Studies of STD clinic attenders have found that circumcised men are less likely to have gonorrhea, syphilis, herpes, candidiasis, and genital ulcer disease (GUD) [1–3]. Age at circumcision has also been reported as a risk factor in penile cancer [4]. Ecological studies report geographic correlations between HIV seroprevalence and the proportion of uncircumcised men in African populations [5,6], but subsequent cross-sectional and prospective studies found an inconsistent association between male circumcision and HIV-1 and HIV-2 infection in men and women [7–9].Item Association between tuberculosis in men and social network structure in Kampala, Uganda(BMC infectious diseases, 2021) Miller, Paige B.; Zalwango, Sarah; Galiwango, Ronald; Kakaire, Robert; Sekandi, Juliet; Steinbaum, Lauren; Drake, John M.; Whalen, Christopher C.; Kiwanuka, NoahGlobally, tuberculosis disease (TB) is more common among males than females. Recent research proposes that differences in social mixing by sex could alter infection patterns in TB. We examine evidence for two mechanisms by which social-mixing could increase men’s contact rates with TB cases. First, men could be positioned in social networks such that they contact more people or social groups. Second, preferential mixing by sex could prime men to have more exposure to TB cases. Methods: We compared the networks of male and female TB cases and healthy matched controls living in Kampala, Uganda. Specifically, we estimated their positions in social networks (network distance to TB cases, degree, betweenness, and closeness) and assortativity patterns (mixing with adult men, women, and children inside and outside the household). Results: The observed network consisted of 11,840 individuals. There were few differences in estimates of node position by sex. We found distinct mixing patterns by sex and TB disease status including that TB cases have proportionally more adult male contacts and fewer contacts with children. Conclusions: This analysis used a network approach to study how social mixing patterns are associated with TB disease. Understanding these mechanisms may have implications for designing targeted intervention strategies in high-burden populations.Item Bone Mineral Density in Antiretroviral Therapy-Naïve HIV-1–Infected Young Adult -Women Using Depot Medroxyprogesterone Acetate or Nonhormonal Contraceptives in Uganda(JBMR plus, 2021) Matovu, Flavia Kiweewa; Nabwana, Martin; Kiwanuka, Noah; Scholes, Delia; Isingel, Esther; Nolan, Monica L; Fowler, Mary G; Musoke, Philippa; Pettifor, John M; Brown, Todd T; Beksinska, Mags EMost studies evaluating BMD in human immunodeficiency virus (HIV)-infected populations have focused on antiretroviral therapy (ART)-experienced patients. In this study, the association between HIV-1 and/or depot medroxyprogesterone acetate (DMPA) and BMD among untreated HIV-1–infected women in a resource-limited setting was assessed before long-term exposure to ART. The data were then compared with that of the 2005–2008 United States National Health and Nutrition Examination Survey data for non-Hispanic White and Black women. Women aged 18–35 years, recruited from health facilities in Kampala, Uganda, were classified based on their combination of HIV-1 status and DMPA use: (i) HIV-1–infected current DMPA users, (ii) HIV-1–infected previous DMPA users, (iii) HIV-1–infected nonhormonal-contraceptive users, and (iv) HIV-uninfected nonhormonal-contraceptive users. All HIV-1– infected women reported being ART-naïve at baseline. BMD was measured at the lumbar spine, total hip, and femoral neck using DXA. Multivariate linear regression was used to assess the association between HIV-1 and/or DMPA and BMD Z-scores. Baseline data were analyzed for 452 HIV-1–infected (220 nonhormonal users, and 177 current and 55 previous DMPA users) and 69 HIV-1– uninfected nonhormonal-contraceptive users. The mean age was 26.1 years (SD, 4.2) with a median duration of DMPA use among current users of 24.0 months [medians (interquartile range), 12-48]. A higher proportion of HIV-1–infected previous (12.7%) or current DMPA users (20.3%) and nonhormonal users (15.0%) had low BMD (Z-score ≤−2 at any of the three sites) compared with agematched HIV-1–uninfected women (2.9%). HIV-1 infection and DMPA use were independently associated with significantly lower mean BMD Z-scores at all sites, with the greatest difference being among HIV-1–infected current DMPA users (5.6%–8.0%) versus uninfected nonhormonal users. Compared with non-Hispanic White and Black women, the Ugandan local reference population had generally lower mean BMD at all sites. Newer treatment interventions are needed to mitigate BMD loss in HIV-1–infected women in resource-limited settings.Item The Cango Lyec Project - Healing the Elephant”: HIV related vulnerabilities of post-conflict affected populations aged 13–49 years living in three Mid-Northern Uganda districts(BMC Infectious Diseases, 2016) Malamba, Samuel S.; Muyinda, Herbert; Spittal, Patricia M.; Ekwaru, John P.; Kiwanuka, Noah; Ogwang, Martin D.; Odong, Patrick; Kitandwe, Paul K.; Katamba, Achilles; Jongbloed, Kate; Sewankambo, Nelson K.; Kinyanda, Eugene; Blair, Alden; Schechter, Martin T.The protracted war between the Government of Uganda and the Lord’s Resistance Army in Northern Uganda (1996–2006) resulted in widespread atrocities, destruction of health infrastructure and services, weakening the social and economic fabric of the affected populations, internal displacement and death. Despite grave concerns that increased spread of HIV/AIDS may be devastating to post conflict Northern Uganda, empirical epidemiological data describing the legacy of the war on HIV infection are scarce. Methods: The ‘Cango Lyec’ Project is an open cohort study involving conflict-affected populations living in three districts of Gulu, Nwoya and Amuru in mid-northern Uganda. Between November 2011 and July 2012, 8 study communities randomly selected out of 32, were mapped and house-to-house census conducted to enumerate the entire community population. Consenting participants aged 13–49 years were enrolled and interviewer-administered data were collected on trauma, depression and socio-demographic-behavioural characteristics, in the local Luo language. Venous blood was taken for HIV and syphilis serology. Multivariable logistic regression was used to determine factors associated with HIV prevalence at baseline. Results: A total of 2954 participants were eligible, of whom 2449 were enrolled. Among 2388 participants with known HIV status, HIV prevalence was 12.2% (95%CI: 10.8-13.8), higher in females (14.6%) than males (8.5%, p < 0.001), higher in Gulu (15.2%) than Nwoya (11.6%, p < 0.001) and Amuru (7.5%, p = 0.006) districts. In this post-conflict period, HIV infection was significantly associated with war trauma experiences (Adj. OR = 2.50; 95%CI: 1.31–4.79), the psychiatric problems of PTSD (Adj. OR = 1.44; 95%CI: 1.06–1.96), Major Depressive Disorder (Adj. OR = 1.89; 95%CI: 1.28–2.80) and suicidal ideation (Adj. OR = 1.87; 95%CI: 1.34–2.61). Other HIV related vulnerabilities included older age, being married, separated, divorced or widowed, residing in an urban district, ulcerative sexually transmitted infections, and staying in a female headed household. There was no evidence in this study to suggest that people with a history of abduction were more likely to be HIV positive. Conclusions: HIV prevalence in this post conflict-affected population is high and is significantly associated with age, trauma, depression, history of ulcerative STIs, and residing in more urban districts. Evidence-based HIV/STI prevention programs and culturally safe, gender and trauma-informed are urgently needed.Item Coercive sex in rural Uganda: Prevalence and associated risk factors(Social Science & Medicine, 2004) Koenig, Michael A.; Lutalo, Tom; Zhao, Feng; Nalugoda, Fred; Kiwanuka, Noah; Wabwire-Mangen, Fred; Kigozi, Godfrey; Sewankambo, Nelson; Wagman, Jennifer; Serwadda, David; Wawer, Maria; Gray, RonaldDespite growing recognition of the problem, relatively little is known about the issue of coercive sex in developing countries. This study presents findings from a community-based survey of 4279 reproductive-aged women in current partnerships in the Rakai District of Uganda carried out in 1998–99. One in four women in our study report having experienced coercive sex with their current male partner, with most women reporting its occasional occurrence. In a regression analysis of risk factors for coercive sex, conventional socio-demographic characteristics emerged as largely unpredictive of the risk of coercive sex. Behavioral risk factors—most notably, younger age of women at first intercourse and alcohol consumption before sex by the male partner—were strongly and positively related to the risk of coercive sex. Coercive sex was also strongly related to perceptions of the male partner’s HIV risk, with women who perceived their partner to be at highest risk experiencing almost three times the risk of coercive sex relative to low risk partnerships. Supplemental analysis of 1-year longitudinal data provides additional support for the hypothesis that coercive sex may frequently be a consequence of women’s perceptions of increased HIV risk for their male partner. The findings of this study are discussed in terms of the need for sexual violence prevention programs more generally in settings such as Uganda, and in terms of the possible importance of incorporating issues of sexual and physical violence within current HIV prevention programs.Item Completion of isoniazid–rifapentine (3HP) for tuberculosis prevention among people living with HIV: Interim analysis of a hybrid type 3 effectiveness–implementation randomized trial(PLoS Med, 2021) Semitala, Fred C.; Kadota, Jillian L.; Musinguzi, Allan; Nabunje, Juliet; Welishe, Fred; Nakitende, Anne; Akello, Lydia; Kamya, Moses R.; Handley, Margaret A.; Katahoire, Anne; Berger, Christopher A.; Kiwanuka, Noah; Katamba, Achilles; Dowdy, David W.; Cattamanchi, AdithyaScaling up shorter regimens for tuberculosis (TB) prevention such as once weekly isoniazid–rifapentine (3HP) taken for 3 months is a key priority for achieving targets set forth in the World Health Organization’s (WHO) END TB Strategy. However, there are few data on 3HP patient acceptance and completion in the context of routine HIV care in sub-Saharan Africa. Methods and findings The 3HP Options Trial is a pragmatic, parallel type 3 effectiveness–implementation randomized trial comparing 3 optimized strategies for delivering 3HP—facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), or informed choice between DOT and SAT using a shared decision-making aid—to people receiving care at a large urban HIV clinic in Kampala, Uganda. Participants and healthcare providers were not blinded to arm assignment due to the nature of the 3HP delivery strategies. We conducted an interim analysis of participants who were enrolled and exited the 3HP treatment period between July 13, 2020 and April 30, 2021. The primary outcome, which was aggregated across trial arms for this interim analysis, was the proportion who accepted and completed 3HP (�11 of 12 doses within 16 weeks of randomization). We used Bayesian inference analysis to estimate the posterior probability that this proportion would exceed 80% under at least 1 of the 3HP delivery strategies, a coprimary hypothesis of the trial. Through April 2021, 684 participants have been enrolled, and 479 (70%) have exited the treatment period. Of these 479 participants, 309 (65%) were women, mean age was 41.9 years (standard deviation (SD): 9.2), and mean time on antiretroviral therapy (ART) was 7.8 years (SD: 4.3). In total, 445 of them (92.9%, 95% confidence interval (CI): [90.2 to 94.9]) accepted and completed 3HP treatment. There were no differences in treatment acceptance and completion by sex, age, or time on ART. Treatment was discontinued due to a documented adverse event (AE) in 8 (1.7%) patients. The probability that treatment acceptance and completion exceeds 80% under at least 1 of the three 3HP delivery strategies was greater than 99%. The main limitations are that the trial was conducted at a single site, and the interim analysis focused on aggregate outcome data to maintain blinding of investigators to arm-specific outcomes. Conclusions 3HP was widely accepted by people living with HIV (PLHIV) in Uganda, and very high levels of treatment completion were achieved in a programmatic setting. These findings show that 3HP can enable effective scale-up of tuberculosis preventive therapy (TPT) in high-burden countries, particularly when delivery strategies are tailored to target known barriers to treatment completion.Item COVID-19 immune signatures in Uganda persist in HIV co-infection and diverge by pandemic phase(Nature Publishing Group, 2024-02) Cummings, Matthew J; Bakamutumaho, Barnabas; Lutwama, Julius J; Owor, Nicholas; Che, Xiaoyu; Astorkia, Maider; Postler, Thomas S; Kayiwa, John; Kiconco, Jocelyn; Muwanga, Moses; Nsereko, Christopher; wamutwe, Emmanuel; Nayiga, Irene; Kyebambe, Stephen; Haumba, Mercy; Bosa, Henry Kyobe; Ocom, Felix; Watyaba, Benjamin; TKikaire, Bernard; Tomoiaga, Alin S; Kisaka, Stevens; Kiwanuka, Noah; Lipkin, W Ian; O'Donnell, Max RLittle is known about the pathobiology of SARS-CoV-2 infection in sub-Saharan Africa, where severe COVID-19 fatality rates are among the highest in the world and the immunological landscape is unique. In a prospective cohort study of 306 adults encompassing the entire clinical spectrum of SARS-CoV-2 infection in Uganda, we profile the peripheral blood proteome and transcriptome to characterize the immunopathology of COVID-19 across multiple phases of the pandemic. Beyond the prognostic importance of myeloid cell-driven immune activation and lymphopenia, we show that multifaceted impairment of host protein synthesis and redox imbalance define core biological signatures of severe COVID-19, with central roles for IL-7, IL-15, and lymphotoxin-α in COVID-19 respiratory failure. While prognostic signatures are generally consistent in SARS-CoV-2/HIV-coinfection, type I interferon responses uniquely scale with COVID-19 severity in persons living with HIV. Throughout the pandemic, COVID-19 severity peaked during phases dominated by A.23/A.23.1 and Delta B.1.617.2/AY variants. Independent of clinical severity, Delta phase COVID-19 is distinguished by exaggerated pro-inflammatory myeloid cell and inflammasome activation, NK and CD8+ T cell depletion, and impaired host protein synthesis. Combining these analyses with a contemporary Ugandan cohort of adults hospitalized with influenza and other severe acute respiratory infections, we show that activation of epidermal and platelet-derived growth factor pathways are distinct features of COVID-19, deepening translational understanding of mechanisms potentially underlying SARS-CoV-2-associated pulmonary fibrosis. Collectively, our findings provide biological rationale for use of broad and targeted immunotherapies for severe COVID-19 in sub-Saharan Africa, illustrate the relevance of local viral and host factors to SARS-CoV-2 immunopathology, and highlight underemphasized yet therapeutically exploitable immune pathways driving COVID-19 severity. Less is known about SARS-CoV-2 infection in unstudied geographical areas such as sub-Saharan Africa. Here the authors use multi-omics to characterize the immune response to SARS-CoV-2 in Uganda and consider how people living with HIV immunologically differentially respond to the virus.Item Defining adequate contact for transmission of Mycobacterium tuberculosis in an African urban environment(BMC public health, 2020) Castellanos, María Eugenia; Zalwango, Sarah; Kakaire, Robert; Ebell, Mark H.; Dobbin, Kevin K.; Sekandi, Juliet; Kiwanuka, Noah; Whalen, Christopher C.The risk of infection from respiratory pathogens increases according to the contact rate between the infectious case and susceptible contact, but the definition of adequate contact for transmission is not standard. In this study we aimed to identify factors that can explain the level of contact between tuberculosis cases and their social networks in an African urban environment. Methods: This was a cross-sectional study conducted in Kampala, Uganda from 2013 to 2017. We carried out an exploratory factor analysis (EFA) in social network data from tuberculosis cases and their contacts. We evaluated the factorability of the data to EFA using the Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO). We used principal axis factoring with oblique rotation to extract and rotate the factors, then we calculated factor scores for each using the weighted sum scores method. We assessed construct validity of the factors by associating the factors with other variables related to social mixing. Results: Tuberculosis cases (N = 120) listed their encounters with 1154 members of their social networks. Two factors were identified, the first named “Setting” captured 61% of the variance whereas the second, named ‘Relationship’ captured 21%. Median scores for the setting and relationship factors were 10.2 (IQR 7.0, 13.6) and 7.7 (IQR 6.4, 10.1) respectively. Setting and Relationship scores varied according to the age, gender, and nature of the relationship among tuberculosis cases and their contacts. Family members had a higher median setting score (13.8, IQR 11.6, 15.7) than non-family members (7.2, IQR 6.2, 9.4). The median relationship score in family members (9.9, IQR 7.6, 11.5) was also higher than in non-family members (6.9, IQR 5.6, 8.1). For both factors, household contacts had higher scores than extra-household contacts (p < .0001). Contacts of male cases had a lower setting score as opposed to contacts of female cases. In contrast, contacts of male and female cases had similar relationship scores. Conclusions: In this large cross-sectional study from an urban African setting, we identified two factors that can assess adequate contact between tuberculosis cases and their social network members. These findings also confirm the complexity and heterogeneity of social mixing.Item Defining an intermediate category of tuberculin skin test: A mixture model analysis of two high-risk populations from Kampala, Uganda(Creative Commons Attribution License, 2021) Woldu, Henok G.; Zalwango, Sarah; Martinez, Leonardo; Castellanos, Maria Eugenia; Kakaire, Robert; Sekandi, Juliet N.; Kiwanuka, Noah; Whalen, Christopher C.One principle of tuberculosis control is to prevent the development of tuberculosis disease by treating individuals with latent tuberculosis infection. The diagnosis of latent infection using the tuberculin skin test is not straightforward because of concerns about immunologic cross reactivity with the Bacille Calmette-Guerin (BCG) vaccine and environmental mycobacteria. To parse the effects of BCG vaccine and environmental mycobacteria on the tuberculin skin test, we estimated the frequency distribution of skin test results in two divisions of Kampala, Uganda, ten years apart. We then used mixture models to estimate parameters for underlying distributions and defined clinically meaningful criteria for latent infection, including an indeterminate category. Using percentiles of two underlying normal distributions, we defined two skin test readings to demarcate three ranges. Values of 10 mm or greater contained 90% of individuals with latent infection; values less than 7.2 mm contained 80% of individuals without infection. Contacts with values between 7.2 and 10 mm fell into an indeterminate zone where it was not possible to assign infection. We conclude that systematic tuberculin skin test surveys within populations at risk, combined with mixture model analysis, may be a reproducible, evidence-based approach to define meaningful criteria for latent tuberculosis infection.Item Designing and Usage of a Low-cost Penile Model for Male Medical Circumcision Skills Training in Rakai, Uganda(Urology, 2011) Kigozi, Godfrey; Nkale, James; Wawer, Maria; Anyokorit, Margaret; Watya, Stephen; Nalugoda, Fred; Kagaayi, Joseph; Kiwanuka, Noah; Mwinike, Joshua; Kighoma, Nehemiah; Nalwoga, Grace K.; Nakigozi, Gertrude F.; Katwalo, Henry; Serwadda, David; Gray, Ronald H.To describe the designing and usage of a locally made low-cost penile model used for male medical circumcision (MMC) skills training. The Rakai MMC training team has experienced a number of challenges during conduct of MMC skills training, one of which was the lack of a model to use for MMC skills training. To address this challenge, the Rakai MMC skills training team has designed and developed a low-cost penile model for use in MMC skills training. The model has been successfully used to demonstrate external penile anatomy, to describe the biological mechanisms through which male circumcision (MC) prevents HIV acquisition, and for demonstration and practice of the MMC procedures. With an initial cost of only $10 and a recurrent cost of $5, this is a cost-efficient and useful penile model that provides a simulation of normal penile anatomy for use in MC training in resource limited settings. It has also been used as a visual aid in preoperative education of patients before receiving male circumcision. The model can be improved and scaled up to develop cheaper commercial penile models.Item Determinants of HIV-1 Load in Subjects with Early and Later HIV Infections, in a General-Population Cohort of Rakai, Uganda(Journal of Infectious Diseases, 2004) Gray, Ronald H.; Li, X.; Wawer, Maria J.; Serwadda, David; Sewankambo, Nelson K.; Wabwire-Mangen, Fred; Lutalo, Tom; Kiwanuka, Noah; Kigozi, Godfrey; Nalugoda, Fred; Meehan, Mary P.; Quinn, Thomas C.Human immunodeficiency virus (HIV) type 1 RNA loads were determined for 256 subjects with early (incident) HIV infection and for 1293 subjects with later (prevalent) HIV infection, in a Ugandan cohort. Prevalent infections were classified as latent (0–1 symptoms) and midstage disease ( 2 symptoms), and deaths were ascribed to acquired immunodeficiency syndrome. Among subjects with incident HIV infection, HIV load did not differ by sex, but, among subjects with prevalent HIV infection, it was higher in males than in females. HIV load was highest in subjects (25–29 years old) with incident HIV infection but increased with age in subjects with prevalent HIV infection. Viremia was higher after serconversion than in latency and increased with more advanced disease. Viremia was increased with genital ulcer disease (GUD) in both subjects with incident infection and in those with prevalent infection, and with herpes simplex virus type 2 seropositivity in subjects with incident HIV infection. GUD was consistently associated with higher HIV loads in subjects with incident and those with prevalent HIV infection, suggesting that treatment of GUD might reduce HIV viremia.Item Developing Medical Technologies for Low-Resource Settings: Lessons From a Wireless Wearable Vital Signs Monitor–neoGuard(Frontiers in Digital Health, 2021) Nantume, Assumpta; Shah, Sona; Cauvel, Teresa; Tomback, Matthew; Kiwanuka, NoahThe neoGuard™ technology is a wireless wearable vital signs monitor attached to a patient's forehead to continuously measure oxygen saturation, pulse rate, respiratory rate and temperature. Developed with feedback from more than 400 health workers, primarily in East Africa, the product has been designed to meet the unique constraints of low-resource settings. This perspective piece by the innovators of neoGuard™ and some of their key partners examines the complicated journey of taking a medical technology from concept through clinical validation and finally to market. By shedding light on some of the most critical steps and common challenges encountered along the pathway to commercialization, the authors hope that their experiences will provide some valuable insights to other aspiring innovators in this space.Item Digital adherence technology for tuberculosis treatment supervision: a stepped-wedge cluster randomized trial(PLoS medicine, 2021) Cattamanchi, Adithya; Crowder, Rebecca; Kityamuwesi, Alex; Kiwanuka, Noah; Lamunu, Maureen; Namale, Catherine; Kunihira Tinka, Lynn; Sanyu Nakate, Agnes; Ggita, Joseph; Turimumahoro, Patricia; Babirye2, Diana; Oyuku, Denis; Berger, Christopher; Tucker, Austin; Patel, Devika; Sammann, Amanda; Stavia, Turyahabwe; Dowdy, David; Katamba, AchillesAdherence to and completion of tuberculosis (TB) treatment remain problematic in many high-burden countries. 99DOTS is a low-cost digital adherence technology that could increase TB treatment completion. Methods and findings We conducted a pragmatic stepped-wedge cluster-randomized trial including all adults treated for drug-susceptible pulmonary TB at 18 health facilities across Uganda over 8 months (1 December 2018–31 July 2019). Facilities were randomized to switch from routine (control period) to 99DOTS-based (intervention period) TB treatment supervision in consecutive months. Patients were allocated to the control or intervention period based on which facility they attended and their treatment start date. AU : IchangedPatientswereallocatedtothecontrolorinterventionperiodbasedontheirtreatmentstartdatetoPatientswereallocatedtothecontroloHealth facility staff and patients were not blinded to the intervention. The primary outcome was TB treatment completion. Due to the pragmatic nature of the trial, the primary analysis was done according to intention-to-treat (ITT) and per protocol (PP) principles. This trial is registered with the Pan African Clinical Trials Registry (PACTR201808609844917). Of 1,913 eligible patients at the 18 health facilities (1,022 and 891 during the control and intervention periods, respectively), 38.0% were women, mean (SD) age was 39.4 (14.4) years, 46.8% were HIV-infected, and most (91.4%) had newly diagnosed TB. In total, 463 (52.0%) patients were enrolled on 99DOTS during the intervention period. In the ITT analysis, the odds of treatment success were similar in the intervention and control periods (adjusted odds ratio [aOR] 1.04, 95% CI 0.68–1.58, p = 0.87). The odds of treatment success did not increase in the intervention period for either men (aOR 1.24, 95% CI 0.73–2.10) or women (aOR 0.67, 95% CI 0.35–1.29), or for either patients with HIV infection (aOR 1.51, 95% CI 0.81–2.85) or without HIV infection (aOR 0.78, 95% CI 0.46–1.32). In the PP analysis, the 99DOTS-based intervention increased the odds of treatment success (aOR 2.89, 95% CI 1.57–5.33, p = 0.001). The odds of completing the intensive phase of treatment and the odds of not being lost to follow-up were similarly improved in PP but not ITT analyses. Study limitations include the likelihood of selection bias in the PP analysis, inability to verify medication dosing in either arm, and incomplete implementation of some components of the intervention. Conclusions 99DOTS-based treatment supervision did not improve treatment outcomes in the overall study population. However, similar treatment outcomes were achieved during the control and intervention periods, and those patients enrolled on 99DOTS achieved high treatment completion. 99DOTS-based treatment supervision could be a viable alternative to directly observed therapy for a substantial proportion of patients with TB.Item Domestic violence in rural Uganda: evidence from a community-based study(Bulletin of the world health organization, 2003) Koenig, Michael A.; Lutalo, Tom; Zhao, Feng; Nalugoda, Fred; Wabwire-Mangen, Fred; Kiwanuka, Noah; Wagman, Jennifer; Serwadda, David; Wawer, Maria; Gray, RonaldAlthough domestic violence is an increasing public health concern in developing countries, evidence from representative, community-based studies is limited. In a survey of 5109 women of reproductive age in the Rakai District of Uganda, 30% of women had experienced physical threats or physical abuse from their current partner—20% during the year before the survey. Three of five women who reported recent physical threats or abuse reported three or more specific acts of violence during the preceding year, and just under a half reported injuries as a result. Analysis of risk factors highlights the pivotal roles of the male partner’s alcohol consumption and his perceived human immunodeficiency virus (HIV) risk in increasing the risk of male against female domestic violence. Most respondents —70% of men and 90% of women—viewed beating of the wife or female partner as justifiable in some circumstances, posing a central challenge to preventing violence in such settings.Item The effects of male circumcision on female partners’ genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda(American journal of obstetrics and gynecology, 2009) Gray, Ronald H.; Kigozi, Godfrey; Serwadda, David; Makumbi, Fredrick; Nalugoda, Fred; Watya, Stephen; Moulton, Laurence; Cheng, Michael Z.; Sewankambo, Nelson K.; Kiwanuka, Noah; Sempijja, Victor; Lutalo, Tom; Kagayii, Joseph; Wabwire-Mangen, Fred; Ridzon, Renée; Bacon, Melanie; Wawer, Maria J.The objective of the study was to assess effects of male circumcision on female genital symptoms and vaginal infections. STUDY DESIGN: Human immunodeficiency virus (HIV)-negative men enrolled in a trial were randomized to immediate or delayed circumcision (control arm). Genital symptoms, bacterial vaginosis (BV), and trichomonas were assessed in HIV-negative wives of married participants. Adjusted prevalence risk ratios (adjPRR) and 95% confidence intervals (CIs) were assessed by multivariable log-binomial regression, intent-to-treat analyses. RESULTS: A total of 783 wives of control and 825 wives of intervention arm men were comparable at enrollment. BV at enrollment was higher in control (38.3%) than intervention arm spouses (30.5%, P .001). At 1 year follow-up, intervention arm wives reported lower rates of genital ulceration (adjPRR, 0.78; 95% CI, 0.63-0.97), but there were no differences in vaginal discharge or dysuria. The risk of trichomonas was reduced in intervention arm wives (adjPRR, 0.52; 95% CI, 0.05- 0.98), as were the risks of any BV (adjPRR, 0.60; 95% CI, 0.38-0.94) and severe BV (prevalence risk ratios, 0.39; 95% CI, 0.24-0.64). CONCLUSION: Male circumcision reduces the risk of ulceration, trichomonas, and BV in female partners.Item Effects of Medical Male Circumcision (MC) on Plasma HIV Viral Load in HIV+ HAART Nai¨ve Men; Rakai, Uganda(PLoS ONE, 2014) Kigozi, Godfrey; Musoke, Richard; Kighoma, Nehemiah; Watya, Stephen; Serwadda, David; Nalugoda, Fred; Kiwanuka, Noah; Wabwire-Mangen, Fred; Tobian, Aaron; Makumbi, Fredrick; Galiwango, Ronald Moses; Sewankambo, Nelson; Nkale, James; Kigozi Nalwoga, Grace; Anyokorit, Margaret; Lutalo, Tom; Henry Gray, Ronald; Wawer, Maria JoanMedical male circumcision (MC) of HIV-infected men may increase plasma HIV viral load and place female partners at risk of infection. We assessed the effect of MC on plasma HIV viral load in HIV-infected men in Rakai, Uganda. 195 consenting HIV-positive, HAART naı¨ve men aged 12 and above provided blood for plasma HIV viral load testing before surgery and weekly for six weeks and at 2 and 3 months post surgery. Data were also collected on baseline social demographic characteristics and CD4 counts. Change in log10 plasma viral load between baseline and follow-up visits was estimated using paired t tests and multivariate generalized estimating equation (GEE).Item Efficacy of convalescent plasma for treatment of COVID-19 in Uganda(BMJ Open Resp Res, 2021) Kirenga, Bruce; Byakika-Kibwika, Pauline; Muttamba, Winters; Kayongo, Alex; Namakula, Olive Loryndah,; Mugenyi, Levicatus; Kiwanuka, Noah; Lusiba, John; Atukunda, Angella; Mugume, Raymond; Ssali, Francis; Ddungu, Henry; Katagira, Winceslaus; Sekibira, Rogers; Kityo, Cissy; Kyeyune, Dorothy; Acana, Susan; Aanyu-Tukamuhebwa, Hellen; Kabweru, Wilberforce; Nakwagala, Fred; Sentalo Bagaya, Bernard; Kimuli, Ivan; Nantanda, Rebecca; Buregyeya, Esther; Byarugaba, Baterana; Olaro, Charles; Mwebesa, Henry; Lutaakome Joloba, Moses; Siddharthan, Trishul; Bazeyo, WilliamConvalescent plasma (CCP) has been studied as a potential therapy for COVID-19, but data on its efficacy in Africa are limited. Objective In this trial we set out to determine the efficacy of CCP for treatment of COVID-19 in Uganda. Measurements Patients with a positive SARS-CoV- 2 reverse transcriptase (RT)-PCR test irrespective of disease severity were hospitalized and randomized to receive either COVID-19 CCP plus standard of care (SOC) or SOC alone. The primary outcome was time to viral clearance, defined as having two consecutive RT-PCR- negative tests by day 28. Secondary outcomes included time to symptom resolution, clinical status on the modified WHO Ordinal Clinical Scale (≥1-point increase), progression to severe/ critical condition (defined as oxygen saturation <93% or needing oxygen), mortality and safety.
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