Characteristics and phenotypes of a COPD cohort from referral hospital clinics in Uganda.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with varied clinical and pathophysiological characteristics. Although there is increasing evidence that COPD in low-income and middle-income countries may have different clinical characteristics from that in high-income countries, little is known about COPD phenotypes in these settings. We describe the clinical characteristics and risk factor profile of a COPD population in Uganda. METHODS: We cross sectionally analysed the baseline clinical characteristics of 323 patients with COPD aged 30 years and above who were attending 2 national referral outpatient facilities in Kampala, Uganda between July 2019 and March 2021. Logistic regression was used to determine factors associated with spirometric disease severity. RESULTS: The median age was 62 years; 51.1% females; 93.5% scored COPD Assessment Test >10; 63.8% modified medical research council (mMRC) >2; 71.8% had wheezing; 16.7% HIV positive; 20.4% had a history of pulmonary tuberculosis (TB); 50% with blood eosinophilic count >3%, 51.7% had 3 or more exacerbations in the past year. Greater severity by Global initiative for Chronic Obstructive Lung Disease (GOLD) stage was inversely related to age (aOR=0.95, 95% CI 0.92 to 0.97), and obesity compared with underweight (aOR=0.25, 95% CI 0.07 to 0.82). Regarding clinical factors, more severe airflow obstruction was associated with SPO2 <93% (aOR=3.79, 95% CI 2.05 to 7.00), mMRC ≥2 (aOR=2.21, 95% CI 1.08 to 4.53), and a history of severe exacerbations (aOR=2.64, 95% CI 1.32 to 5.26). CONCLUSION: Patients with COPD in this population had specific characteristics and risk factor profiles including HIV and TB meriting tailored preventative approaches. Further studies are needed to better understand the pathophysiological mechanisms at play and the therapeutic implications of these findings.

The burden of severe asthma in sub-Saharan Africa: Findings from the African Severe Asthma Project.

Background: Severe asthma is associated with high morbidity, mortality, and health care utilization, but its burden in Africa is unknown. Objective: We sought to determine the burden (prevalence, mortality, and activity and work impairment) of severe asthma in 3 countries in East Africa: Uganda, Kenya, and Ethiopia. Methods: Using the American Thoracic Society/European Respiratory Society case definition of severe asthma, we analyzed for the prevalence of severe asthma (requiring Global Initiative for Asthma [GINA] steps 4-5 asthma medications for the previous year to achieve control) and severe refractory asthma (remains uncontrolled despite treatment with GINA steps 4-5 asthma medications) in a cohort of 1086 asthma patients who had been in care for 12 months and had received all GINA-recommended medications. Asthma control was assessed by the asthma control questionnaire (ACQ). Results: Overall, the prevalence of severe asthma and severe refractory asthma was 25.6% (95% confidence interval [CI], 23.1-28.3) and 4.6% (95% CI, 3.5-6.0), respectively. Patients with severe asthma were (nonsevere vs severe vs severe refractory) older (39, 42, 45 years, P = .011), had high skin prick test reactivity (67.1%, 76.0%, 76.0%, P = .004), had lower forced expiratory volume in 1 second percentage (81%, 61%, 55.5%, P < .001), had lower quality of life score (129, 127 vs 121, P < .001), and had higher activity impairment (10%, 30%, 50%, P < .001). Factors independently associated with severe asthma were hypertension comorbidity; adjusted odds ratio 2.21 (1.10-4.47), P = .027, high bronchial hyperresponsiveness questionnaire score; adjusted odds ratio 2.16 (1.01-4.61), P = .047 and higher ACQ score at baseline 2.80 (1.55-5.08), P = .001. Conclusion: The prevalence of severe asthma in Africa is high and is associated with high morbidity and poor quality of life.

Isoniazid preventive therapy completion between July-September 2019: A comparison across HIV differentiated service delivery models in Uganda.

BACKGROUND: Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLHIV). To prevent TB among PLHIV, the Ugandan national guidelines recommend Isoniazid Preventive Therapy (IPT) across differentiated service delivery (DSD) models, an effective way of delivering ART. DSD models include Community Drug Distribution Point (CDDP), Community Client-led ART Delivery (CCLAD), Facility-Based Individual Management (FBIM), Facility-Based Group (FBG), and Fast Track Drug Refill (FTDR). Little is known about the impact of delivering IPT through DSD. METHODS: We reviewed medical records of PLHIV who initiated IPT between June-September 2019 at TASO Soroti (TS), Katakwi Hospital (KH) and Soroti Regional Referral Hospital (SRRH). We defined IPT completion as completing a course of isoniazid within 6-9 months. We utilized a modified Poisson regression to compare IPT completion across DSD models and determine factors associated with IPT completion in each DSD model. RESULTS: Data from 2968 PLHIV were reviewed (SRRH: 50.2%, TS: 25.8%, KH: 24.0%); females: 60.7%; first-line ART: 91.7%; and Integrase Strand Transfer Inhibitor (INSTI)-based regimen: 61.9%. At IPT initiation, the median age and duration on ART were 41.5 (interquartile range [IQR]; 32.3-50.2) and 6.0 (IQR: 3.7-8.6) years, respectively. IPT completion overall was 92.8% (95%CI: 91.8-93.7%); highest in CDDP (98.1%, 95%CI: 95.0-99.3%) and lowest in FBG (85.8%, 95%CI: 79.0-90.7%). Compared to FBIM, IPT completion was significantly higher in CDDP (adjusted rate ratio [aRR] = 1.15, 95%CI: 1.09-1.22) and CCLAD (aRR = 1.09, 95% CI 1.02-1.16). In facility-based models, IPT completion differed between sites (p<0.001). IPT completion increased with age for FBIM and CCLAD and was lower among female participants in the CCLAD (aRR = 0.82, 95%CI 0.67-0.97). CONCLUSION: IPT completion was high overall but highest in community-based models. Our findings provide evidence that supports integration of IPT within DSD models for ART delivery in Uganda and similar settings.

Effect of the "universal test and treat" policy on the characteristics of persons registering for HIV care and initiating antiretroviral therapy in Uganda.

We examined the effect of the Universal Test and Treat (UTT) policy on the characteristics of people living with HIV (PLHIV) at enrolment in HIV care and initiation of antiretroviral therapy (ART) in Uganda using data from 11 nationally representative clinics of The AIDS Support Organisation (TASO). We created two retrospective PLHIV cohorts: pre-UTT (2004-2016), where ART initiation was conditional on CD4 cell count and UTT (2017-2022), where ART was initiated regardless of World Health Organisation (WHO) clinical stage or CD4 cell count. We used a two-sample test of proportions and Wilcoxon rank-sum test to compare proportions and medians, respectively, between the cohorts. A total of 244,693 PLHIV were enrolled at the clinics [pre-UTT, 210,251 (85.9%); UTT, 34,442 (14.1%)]. Compared to the pre-UTT cohort, the UTT cohort had higher proportions of PLHIV that were male (p < 0.001), aged 18-29 years (p < 0.001), aged >69 years, never married (p < 0.001), and educated to primary (p < 0.001) and post-primary (p < 0.001) school level at enrolment in HIV care and ART initiation. Overall, 97.9% of UTT PLHIV initiated ART compared to 45.2% under pre-UTT. The median time from enrolment in HIV care to ART initiation decreased from 301 [interquartile range (IQR): 58-878] pre-UTT to 0 (IQR: 0-0) under UTT. The median CD4 count at ART initiation increased from 254 cells/µL pre-UTT to 482 cells/µL under UTT (p < 0.001). Compared to the pre-UTT cohort, the UTT cohort had higher proportions of PLHIV with a CD4 count >500 cells/µL (47.3% vs. 13.2%, p < 0.001) and WHO stage 1 (31.7% vs. 4.5%, p < 0.001) at ART initiation. Adoption of the UTT policy in Uganda was successful in enrolling previously unreached individuals, such as men and younger and older adults, as well as those with less advanced HIV disease. Future research will investigate the effect of UTT on long-term outcomes such as retention in care, HIV viral suppression, morbidity, and mortality.

Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study.

Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19-0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53-5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54-1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.

Regulation of community advisory boards during conduct of clinical trials in Uganda: a qualitative study involving stakeholders.

BACKGROUND: Community advisory structures such as Community Advisory Boards (CABs) play an important role of helping researchers to better understand the community at each phase of the clinical trial. CABs can be a source of accurate information on the community, its perception of proposed research and may identify factors that make community members vulnerable to the problem under investigation. Although CABs help to build mutually beneficial relationships between the researcher(s) and the communities in which the clinical trial is being implemented, effective engagement would require ethical guidance and regulatory oversight. The study assessed the stakeholders' perspectives regarding the regulatory oversight of CABs in Uganda. METHODS: This was an exploratory study employing qualitative methods of data collection and analysis. Key informant interviews (KIIs) with the trial investigators, CAB chairpersons, community liaison officers, regulators and Research Ethics Committee (REC) chairpersons were conducted. A KII guide was designed and utilized during key informant interviews. The guide included questions on role of investigators and CAB members in clinical trials; challenges of community engagement; facilitation of CABs; regulatory oversight of CABs; work relationships between investigators and CABs; and opinions on how community trials should be conducted among others. All interviews were conducted in English. Qualitative data were transcribed verbatim. A code book was generated based on the transcripts and study objectives. Thematic analysis was used to analyze data and identify themes. Atlas ti was used to support data analysis. RESULTS: Of the 34 respondents, 35.3% were investigators, 32.3% CAB chairpersons, 23.5% research regulators/REC Chairs and 8.8% community liaison officers. The findings of the study revealed that CABs are appointed by the research institution/researcher, operate under the guidance of the researcher with limited independence. Additionally, the CABs provide voluntary service and lack guidelines or regulatory oversight. Four themes emerged. CONCLUSION: The operations and activities of CABs are not regulated by the national regulators or RECs. The regulatory oversight of CABs should be based on contextualized ethical guidelines. Need for additional training in research ethics, community engagement and sensitization on available ethics guidelines for research.

Modelling longitudinal binary outcomes with outcome dependent observation times: an application to a malaria cohort study.

BACKGROUND : In spite of the global reduction of 21% in malaria incidence between 2010 and 2015, the disease still threatens many lives of children and pregnant mothers in African countries. A correct assessment and evaluation of the impact of malaria control strategies still remains quintessential in order to eliminate the disease and its burden. Malaria follow-up studies typically involve routine visits at pre-scheduled time points and/or clinical visits whenever individuals experience malaria-like symptoms. In the latter case, infection triggers outcome assessment, thereby leading to outcome-dependent sampling (ODS). Commonly used methods to analyze such longitudinal data ignore ODS and potentially lead to biased estimates of malaria-specific transmission parameters, hence, inducing an incorrect assessment and evaluation of malaria control strategies. METHODS : In this paper, a new method is proposed to handle ODS by use of a joint model for the longitudinal binary outcome measured at routine visits and the clinical event times. The methodology is applied to malaria parasitaemia data from a cohort of [Formula: see text] Ugandan children aged 0.5-10 years from 3 regions (Walukuba-300 children, Kihihi-355 children and Nagongera-333 children) with varying transmission intensities (entomological inoculation rate equal to 2.8, 32 and 310 infectious bites per unit year, respectively) collected between 2011-2014. RESULTS : The results indicate that malaria parasite prevalence and force of infection (FOI) increase with age in the region of high malaria intensity with highest FOI in age group 5-10 years. For the region of medium intensity, the prevalence slightly increases with age and the FOI for the routine process is highest in age group 5-10 years, yet for the clinical infections, the FOI gradually decreases with increasing age. For the region with low intensity, both the prevalence and FOI peak at the age of 1 year after which the former remains constant with age yet the latter suddenly decreases with age for the clinically observed infections. CONCLUSION : Malaria parasite prevalence and FOI increase with age in the region of high malaria intensity. In all study sites, both the prevalence and FOI are highest among previously asymptomatic children and lowest among their symptomatic counterparts. Using a simulation study inspired by the malaria data at hand, the proposed methodology shows to have the smallest bias, especially when consecutive positive malaria parasitaemia presence results within a time period of 35 days were considered to be due to the same infection.

Cognitive functioning and prevalence of seizures among older persons in Uganda: A hospital-based, cross-sectional study.

There is limited data on the prevalence of seizures and dementia among older persons in Uganda. We evaluated cognitive functioning, and the prevalence and factors associated with seizures among older persons attending an outpatient medical clinic in Uganda. We randomly selected older adults (60 years and above) attending Kiruddu National Referral Hospital medical outpatient clinics between October 2020 and March 2021. We excluded individuals with a history of head injury, brain tumors, mental retardation, co-morbidity with HIV and patients who have had recent brain surgery. Cognitive functioning was assessed using the Identification for Dementia in Elderly Africans (IDEA) tool. We enrolled 407 participants, with a median (inter-quartile range) age of 67 (64-73) years. Majority were female (n = 292, 71.7%). The prevalence of seizure was 1.5% (95% confidence interval [CI]: 0.7-3.3). All 6 participants reported generalized tonic-clonic seizure type. Self-reported seizure was associated with being female (adjusted prevalence ratio [aPR]: 0.79, 95%CI: 0. 67-0.93, P = .02) and residing in Mukono district (aPR: 17.26, 95%CI: 1.64-181.55, P = .018). Overall, 114 (28.1%) participants had cognitive deficit; 9 (2.2%) dementia and 105 (25.9%) impaired cognition. Cognitive deficit was independently associated with female gender (aPR: 0.61, 95%CI: 0.44-0.85, P = .003), formal employment (aPR: 0.53, 95%CI: 0.35-0.81, P = .003), age 70-74 (aPR: 1.69, 95%CI: 1.00-2.86, P = .049), and ≥ 75 years (aPR: 2.81, 95%CI: 1.71-4.61, P = .001). Prevalence of seizures among participants with cognitive deficit was 5.3% (6/114). Among older persons attending a medical clinic in Uganda, almost one-third had cognitive deficit with seizure prevalence being higher among these individuals.

Effect of universal test and treat on retention and mortality among people living with HIV-infection in Uganda: An interrupted time series analysis.

BACKGROUND: Few studies have analysed the effect of HIV universal test and treat (UTT) on retention and mortality among people living with HIV (PLHIV) in routine care. We examined six-month retention and mortality at 11 health facilities (HFs) run by a large NGO, The AIDS Support Organisation (TASO), before and after UTT. METHODS: We used a quasi-experimental study using patient data extracted from 11 TASO HFs. Two periods, one before UTT (2015-2016) and the other during UTT (2017-2018) were compared. The primary outcome was six-month retention defined as the proportion of PLHIV who were alive and in care at six months from enrolment. The secondary outcome was six-month mortality defined as the proportion of PLHIV who died within six months from enrolment. We performed an interrupted time series analysis using graphical aids to study trends in six-month retention and mortality and a segmented regression to evaluate the effect of UTT. We used a generalized linear mixed model (GLMM) and generalized estimating equations (GEE) to account for facility-level clustering. RESULTS: Of the 20,171 PLHIV registered between 2015 and 2018 and included in the analysis, 12,757 (63.2%) were enrolled during the UTT period. 5256/7414 (70.9%) of the pre-UTT period compared to 12239/12757 (95.9%) of the UTT were initiated on ART treatment with 6 months from enrolment. The median time from enrolment to initiating ART was 14 (interquartile range (IQR): 0-31) days for the pre-UTT compared to 0 (IQR: 0-0) days for the UTT period. The median age at enrolment was 32.5 years for the pre-UTT and 35.0 years for the UTT period. Overall, the six-month retention just after scale-up of UTT, increased by 9.2 percentage points (p = 0.002) from the baseline value of 82.6% (95% CI: 77.6%-87.5%) but it eventually decreased at a rate 1.0 percentage point (p = 0.014) for cohorts recruited each month after UTT. The baseline six-month mortality was 3.3% (95% CI: 2.4%-4.2%) and this decreased by 1.6 percentage points (p = 0.003) immediately after UTT. The six-month mortality continued decreasing at a rate of 0.1 percentage points (p = 0.002) for cohorts enrolled each month after UTT. Retention differed between some health facilities with Rukungiri HF having the highest and Soroti the lowest retention. Retention was slightly higher among males and younger people. Mortality was highest among people aged 50 years and more. The effect of UTT on retention and mortality was similar across sex and age groups. CONCLUSION: Overall, UTT significantly led to an immediate increase in retention and decrease in mortality among PLHIV enrolled in HIV care from 11 HFs run by TASO in Uganda. However, retention (and mortality) significantly decreased for cohorts enrolled each month after UTT. Retention was highest in Rukungiri and lowest in Soroti HFs and slightly higher in males and younger people. Mortality was highest in older patients and lowest in adolescents. We recommend for innovative interventions to improve the overall retention particularly in facilities reporting low retention in order to achieve the UNAIDS 2030 target of 95-95-95.

Incidence of tuberculosis among PLHIV on antiretroviral therapy who initiated isoniazid preventive therapy: A multi-center retrospective cohort study.

INTRODUCTION: Isoniazid preventive therapy (IPT) is effective in treating tuberculosis (TB) infection and hence limiting progression to active disease. However, the durability of protection, associated factors and cost-effectiveness of IPT remain uncertain in low-and-middle income countries, Uganda inclusive. The Uganda Ministry of health recommends a single standard-dose IPT course for eligible people living with HIV (PLHIV). In this study we determined the incidence, associated factors and median time to TB diagnosis among PLHIV on Antiretroviral therapy (ART) who initiated IPT. MATERIALS AND METHODS: We conducted a retrospective cohort study at eleven The AIDS Support Organization (TASO) centers in Uganda. We reviewed medical records of 2634 PLHIV on ART who initiated IPT from 1st January 2016 to 30th June 2018, with 30th June 2021 as end of follow up date. We analyzed study data using STATA v.16. Incidence rate was computed as the number of new TB cases divided by the total person months. A Frailty model was used to determine factors associated with TB incidence. RESULTS: The 2634 individuals were observed for 116,360.7 person months. IPT completion rate was 92.8%. Cumulative proportion of patients who developed TB in this cohort was 0.83% (22/2634), an incidence rate of 18.9 per 100,000 person months. The median time to TB diagnosis was 18.5 months (minimum- 0.47; maximum- 47.3, IQR: 10.1-32.4). World Health Organization (WHO) HIV clinical stage III (adjusted hazard ratio (aHR) 95%CI: 3.66 (1.08, 12.42) (P = 0.037) and discontinuing IPT (aHR 95%CI: 25.96(4.12, 169.48) (p = 0.001)), were associated with higher odds of TB diagnosis compared with WHO clinical stage II and IPT completion respectively. CONCLUSION: Incidence rates of TB were low overtime after one course of IPT, and this was mainly attributed to high completion rates.

Capacity of community advisory boards for effective engagement in clinical research: a mixed methods study.

BACKGROUND: Community engagement is a key component in health research. One of the ways health researchers ensure community engagement is through Community Advisory Boards (CABs). The capacity of CABs to properly perform their role in clinical research has not been well described in many resource limited settings. In this study, we assessed the capacity of CABs for effective community engagement in Uganda. METHODS: We conducted a cross sectional study with mixed methods. We used structured questionnaires and key informant interviews (KII) to collect data from CAB members, trial investigators, and community liaison officers. For quantitative data, we used descriptive statistics while for qualitative data we used content analysis. RESULTS: Seventy three CAB members were interviewed using structured questionnaires; 58.9% males, median age 49 years (IQR 24-70), 71.2% had attained tertiary education, 42.5% never attended any research ethics training, only 26% had a training in human subject protection, 30.1% had training in health research, 50.7% never attended any training about the role of CABs, and 72.6% had no guidelines for their operation. On the qualitative aspect, 24 KIIs cited CAB members to have some skills and ability to understand and review study documents, offer guidance on community norms and expectations and give valuable feedback to the investigators. However, challenges like limited resources, lack of independence and guidelines, and knowledge gaps about research ethics were cited as hindrances of CABs capacity. CONCLUSION: Though CABs have some capacity to perform their role in the Ugandan setting, their functionality is limited by lack of resources to facilitate their work, lack of independence, lack of guidelines for their operations and limited knowledge regarding issues of research ethics and protection of the rights of trial participants.

Feasibility of using a mobile App to monitor and report COVID-19 related symptoms and people's movements in Uganda.

BACKGROUND: Feasibility of mobile Apps to monitor diseases has not been well documented particularly in developing countries. We developed and studied the feasibility of using a mobile App to collect daily data on COVID-19 symptoms and people's movements. METHODS: We used an open source software "KoBo Toolbox" to develop the App and installed it on low cost smart mobile phones. We named this App "Wetaase" ("protect yourself"). The App was tested on 30 selected households from 3 densely populated areas of Kampala, Uganda, and followed them for 3 months. One trained member per household captured the data in the App for each enrolled member and uploaded it to a virtual server on a daily basis. The App is embedded with an algorithm that flags participants who report fever and any other COVID-19 related symptom. RESULTS: A total of 101 participants were enrolled; 61% female; median age 23 (interquartile range (IQR): 17-36) years. Usage of the App was 78% (95% confidence interval (CI): 77.0%-78.8%). It increased from 40% on day 1 to a peak of 81% on day 45 and then declined to 59% on day 90. Usage of the App did not significantly vary by site, sex or age. Only 57/6617 (0.86%) records included a report of at least one of the 17 listed COVID-19 related symptoms. The most reported symptom was flu/runny nose (21%) followed by sneezing (15%), with the rest ranging between 2% and 7%. Reports on movements away from home were 45% with 74% going to markets or shops. The participants liked the "Wetaase" App and recommended it for use as an alert system for COVID-19. CONCLUSION: Usage of the "Wetaase" App was high (78%) and it was similar across the three study sites, sex and age groups. Reporting of symptoms related to COVID-19 was low. Movements were mainly to markets and shops. Users reported that the App was easy to use and recommended its scale up. We recommend that this App be assessed at a large scale for feasibility, usability and acceptability as an additional tool for increasing alerts on COVID-19 in Uganda and similar settings.

Impact of socio-economic factors on Tuberculosis treatment outcomes in north-eastern Uganda: a mixed methods study.

BACKGROUND: Tuberculosis (TB) is a major public health problem and at 48%, Karamoja in North-Eastern Uganda has the lowest treatment success rate nationally. Addressing the social determinants of TB is crucial to ending TB. This study sought to understand the extent and ways in which socio-economic factors affect TB treatment outcomes in Karamoja. METHODS: We conducted a convergent parallel mixed methods study in 10 TB Diagnostic and Treatment Units. The study enrolled former TB patients diagnosed with drug-susceptible TB between April 2018 and March 2019. Unit TB and laboratory registers were reviewed to identify pre-treatment losses to follow-up. Four focus group discussions with former TB patients and 18 key informant interviews with healthcare workers were conducted. Principle component analysis was used to generate wealth quintiles that were compared to treatment outcomes using the proportion test. The association between sociodemographic characteristics and TB treatment outcomes was evaluated using the chi-square test and multiple logistic regression. RESULTS: A total of 313 participants were randomly selected from 1184 former TB patients recorded in the unit TB registers. Of these, 264 were contacted in the community and consented to join the study: 57% were male and 156 (59.1%) participants had unsuccessful treatment outcomes. The wealthiest quintile had a 58% reduction in the risk of having an unsuccessful treatment outcome (adj OR = 0.42, 95% CI 0.18-0.99, p = 0.047). People who were employed in the informal sector (adj OR = 4.71, 95% CI 1.18-18.89, p = 0.029) and children under the age of 15 years who were not in school or employed (adj OR = 2.71, 95% CI 1.11-6.62, p = 0.029) had significantly higher odds of unsuccessful treatment outcome. Analysis of the pre-treatment loss to follow-up showed that 17.2% of patients with pulmonary bacteriologically confirmed TB did not initiate treatment with a higher proportion among females (21.7%) than males (13.5%). Inadequate food, belonging to migratory communities, stigma, lack of social protection, drug stock-outs and transport challenges affected TB treatment outcomes. CONCLUSIONS: This study confirmed that low socio-economic status is associated with poor TB treatment outcomes emphasizing the need for multi- and cross-sectoral approaches and socio-economic enablers to optimise TB care.

Integrating health services for HIV infection, diabetes and hypertension in sub-Saharan Africa: a cohort study.

BACKGROUND: HIV, diabetes and hypertension have a high disease burden in sub-Saharan Africa. Healthcare is organised in separate clinics, which may be inefficient. In a cohort study, we evaluated integrated management of these conditions from a single chronic care clinic. OBJECTIVES: To determined the feasibility and acceptability of integrated management of chronic conditions in terms of retention in care and clinical indicators. DESIGN AND SETTING: Prospective cohort study comprising patients attending 10 health facilities offering primary care in Dar es Salaam and Kampala. INTERVENTION: Clinics within health facilities were set up to provide integrated care. Patients with either HIV, diabetes or hypertension had the same waiting areas, the same pharmacy, were seen by the same clinical staff, had similar provision of adherence counselling and tracking if they failed to attend appointments. PRIMARY OUTCOME MEASURES: Retention in care, plasma viral load. FINDINGS: Between 5 August 2018 and 21 May 2019, 2640 patients were screened of whom 2273 (86%) were enrolled into integrated care (832 with HIV infection, 313 with diabetes, 546 with hypertension and 582 with multiple conditions). They were followed up to 30 January 2020. Overall, 1615 (71.1%)/2273 were female and 1689 (74.5%)/2266 had been in care for 6 months or more. The proportions of people retained in care were 686/832 (82.5%, 95% CI: 79.9% to 85.1%) among those with HIV infection, 266/313 (85.0%, 95% CI: 81.1% to 89.0%) among those with diabetes, 430/546 (78.8%, 95% CI: 75.4% to 82.3%) among those with hypertension and 529/582 (90.9%, 95% CI: 88.6 to 93.3) among those with multimorbidity. Among those with HIV infection, the proportion with plasma viral load <100 copies/mL was 423(88.5%)/478. CONCLUSION: Integrated management of chronic diseases is a feasible strategy for the control of HIV, diabetes and hypertension in Africa and needs evaluation in a comparative study.

Sexual-risk behaviours and HIV and syphilis prevalence among in- and out-of-school adolescent girls and young women in Uganda: A cross-sectional study.

BACKGROUND: Adolescent girls and young women (AGYW) are at increased risk of sexually transmitted infections (STIs). We assessed sexual-risk behaviours and HIV and syphilis prevalence among AGYW in Uganda to inform the design of target-specific risk-reduction interventions. METHODS: This analysis utilizes data from 8,236 AGYW aged 10-24 years, collected in 20 districts, between July and August 2018. AGYW engaged in sexual-risk behaviour if they: a) reported a history of STIs; or b) had their sexual debut before age 15; or c) engaged in sex with 2+ partners in the past 12 months; or c) did not use or used condoms inconsistently with their most recent partners. We diagnosed HIV using DetermineTM HIV-1/2, Stat-PakTM HIV-1/2 and SD Bioline. We used SD Bioline Syphilis test kits to diagnose syphilis and Treponema Pallidum Hemagglutination Assay for confirmatory syphilis testing. Comparison of proportions was done using Chi-square (χ2) tests. Data were analysed using STATA (version 14.1). RESULTS: Of 4,488 AGYW (54.5%) that had ever had sex, 12.9% (n = 581) had their sexual debut before age 15; 19.1% (n = 858) reported a history of STIs. Of those that had ever had sex, 79.6% (n = 3,573) had sex in the 12 months preceding the survey; 75.6% (n = 2,707) with one (1) and 24.2% (n = 866) with 2+ partners. Condom use with the most recent sexual partner was low, with only 20.4% (n = 728) reporting consistent condom use while 79.6% (n = 2,842) reported inconsistent or no condom use. In-school AGYW were significantly less likely to have ever had sex (35.6% vs. 73.6%, P<0.001), to have had sexual debut before age 15 (7.7% vs. 15.5%, P<0.001) or to engage in sex with 2+ partners (5.3% vs. 15.8%, P<0.001). Consistent condom use was significantly higher among in-school than out-of-school AGYW (40.1% vs. 12.7%, P<0.001). Overall, 1.7% (n = 143) had HIV while 1.3% (n = 104) had syphilis. HIV and syphilis prevalence was higher among out-of-school than in-school AGYW (HIV: 2.6% vs. 0.9%; syphilis: 2.1% vs. 0.5%, respectively). CONCLUSION: In-school AGYW engaged in more protective sexual behaviors and had less HIV and syphilis than their out-of-school counterparts. These findings suggest a need for target-specific risk-reduction interventions stratified by schooling status.

Efficacy of convalescent plasma for treatment of COVID-19 in Uganda.

RATIONALE: Convalescent 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 hospitalised and randomised 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. MAIN RESULTS: A total of 136 patients were randomised, 69 to CCP+SOC and 67 to SOC only. The median age was 50 years (IQR: 38.5-62.0), 71.3% were male and the median duration of symptom was 7 days (IQR=4-8). Time to viral clearance was not different between the CCP+SOC and SOC arms (median of 6 days (IQR=4-11) vs 4 (IQR=4-6), p=0.196). There were no statistically significant differences in secondary outcomes in CCP+SOC versus SOC: time to symptom resolution (median=7 (IQR=5-7) vs 7 (IQR=5-10) days, p=0.450), disease progression (9 (22.0%) vs 7 (24.0%) patients, p=0.830) and mortality (10 (14.5%) vs 8 (11.9%) deaths, p=0.476). CONCLUSION: In this African trial, CCP therapy did not result in beneficial virological or clinical improvements. Further trials are needed to determine subgroups of patients who may benefit from CCP in Africa.Trial registration number NCT04542941.

Feasibility of collecting and processing of COVID-19 convalescent plasma for treatment of COVID-19 in Uganda.

INTRODUCTION: Evidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of COVID-19 is increasingly emerging. However, very few African countries have undertaken the collection and processing of CCP. The aim of this study was to assess the feasibility of collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for treatment of COVID-19 in Uganda. METHODS: In a cross-sectional study, persons with documented evidence of recovery from COVID-19 in Uganda were contacted and screened for blood donation via telephone calls. Those found eligible were asked to come to the blood donation centre for further screening and consent. Whole blood collection was undertaken from which plasma was processed. Plasma was tested for transfusion transmissible infections (TTIs) and anti-SARS CoV-2 antibody titers. SARS-CoV-2 testing was also done on nasopharyngeal swabs from the donors. RESULTS: 192 participants were contacted of whom 179 (93.2%) were eligible to donate. Of the 179 eligible, 23 (12.8%) were not willing to donate and reasons given included: having no time 7(30.4%), fear of being retained at the COVID-19 treatment center 10 (43.5%), fear of stigma in the community 1 (4.3%), phobia for donating blood 1 (4.3%), religious issues 1 (4.4%), lack of interest 2 (8.7%) and transport challenges 1 (4.3%). The median age was 30 years and females accounted for 3.7% of the donors. A total of 30 (18.5%) donors tested positive for different TTIs. Antibody titer testing demonstrated titers of more than 1:320 for all the 72 samples tested. Age greater than 46 years and female gender were associated with higher titers though not statistically significant. CONCLUSION: CCP collection and processing is possible in Uganda. However, concerns about stigma and lack of time, interest or transport need to be addressed in order to maximize donations.

Incidence and predictors of COPD mortality in Uganda: A 2-year prospective cohort study.

BACKGROUND: Data is lacking on outcomes among COPD patients in sub-Saharan Africa. The objective of the study was to assess the incidence and predictors of mortality among COPD patients enrolled in the Uganda Registry for Asthma and COPD. RESEARCH QUESTION: What is the Incidence and predictors of mortality among COPD patients in Uganda? STUDY DESIGN AND METHODS: Individuals with a diagnosis of COPD at six hospitals in Uganda were enrolled into the registry, and followed every six months. Mortality was ascertained through post-mortem reports and verbal autopsies. Mortality rates (MR), mortality rate ratios (MRR), and hazard ratios (HR) were computed to assess associations between socio-demographic, behavioural, and clinical characteristics at enrolment into the registry and mortality up to two years after. RESULTS: We enrolled 296 COPD patients. Median age was 60 years, and 51·3% were male. The overall mortality rate was 95·90 deaths/1000 person-years. COPD severity by post-bronchodilator FEV1 was the strongest risk factor for mortality. Compared to stage 1, adjusted hazard ratios were as follows for stage 4: 9·86 (95%CI: 1·70-57·14, p = 0·011), stage 3: 6·16 (95%CI: 1·25-30·32, p = 0·025), and stage 2: 1·76 (95%CI: 0·33-9·48, p = 0·51). Underweight patients had a higher incidence of mortality compared to normal weight patients (MRR: 3·47 (95%CI: 1·45-8·31, p = 0·0026). CONCLUSION: Among COPD patients in Uganda, two-year mortality is high, and disease severity at baseline was the strongest risk factor for mortality. Our findings suggest the need for early, accurate, diagnosis and management of COPD, to potentially improve survival.

Estimating the optimal interval between rounds of indoor residual spraying of insecticide using malaria incidence data from cohort studies.

BACKGROUND: Indoor residual spraying (IRS) reduces vector densities and malaria transmission, however, the most effective spraying intervals for IRS have not been well established. We estimated the optimal timing interval for IRS using a statistical approach. METHODS: Six rounds of IRS were implemented in Tororo District, a historically high malaria transmission setting in Uganda, during the study period (3 rounds with bendiocarb active ingredient (Ficam®): December 2014 to December 2015, and 3 rounds with pirimiphos methyl active ingredient (Actellic 300®CS): June 2016 to July 2018). A generalized additive model was used to estimate the optimal timing interval for IRS based on the predicted malaria incidence. The model was fitted to clinical incidence data from a cohort of children aged 0.5-10 years from selected households observed throughout the study period. RESULTS: 494 children, 67% aged less than 5 years at enrolment were analysed. Six-months period incidence of malaria decreased from 2.96 per person-years at the baseline to 1.74 following the first round of IRS and then to 0.02 after 6 rounds of IRS. The optimal time interval for IRS differed between bendiocarb and pirimiphos methyl and by IRS round. To retain an optimum impact, bendiocarb would require respraying 17 (95% CI: 14.2-21.0) weeks after application whereas pirimiphos methyl could remain impactful for 40 (95% CI: 37.0-42.8) weeks, although in the final year this estimates 36 (95% CI: 32.7-37.7) weeks. However, we could not estimate from the data the optimal time after the second and third rounds of bendiocarb and after the second round of pirimiphos methyl. Neither the amount of rainfall nor the EIR nor the distribution of nets were found to be statistically significant for determining the time period between spray rounds. CONCLUSION: In our setting, the effect of the two IRS products was distinct. Statistically, pirimiphos methyl provided a longer window of protection than bendiocarb, although impact varied between different spray rounds and years which was not explained by rainfall or EIR or distribution of nets in our statistical approach. Understanding the effectiveness of IRS and how long it lasts can help for planning campaigns, but one should consider the financial cost and insecticide resistance. Monitoring the timing of spray campaigns using clinical incidence could be repeated in future programs to help determine the average period of protectivity of these products.

Households experiencing catastrophic costs due to tuberculosis in Uganda: magnitude and cost drivers.

BACKGROUND: Tuberculosis (TB) patients in Uganda incur large costs related to the illness, and while seeking and receiving health care. Such costs create access and adherence barriers which affect health outcomes and increase transmission of disease. The study ascertained the proportion of Ugandan TB affected households incurring catastrophic costs and the main cost drivers. METHODS: A cross-sectional survey with retrospective data collection and projections was conducted in 2017. A total of 1178 drug resistant (DR) TB (44) and drug sensitive (DS) TB patients (1134), 2 weeks into intensive or continuation phase of treatment were consecutively enrolled across 67 randomly selected TB treatment facilities. RESULTS: Of the 1178 respondents, 62.7% were male, 44.7% were aged 15-34 years and 55.5% were HIV positive. For each TB episode, patients on average incurred costs of USD 396 for a DS-TB episode and USD 3722 for a Multi drug resistant tuberculosis (MDR TB) episode. Up to 48.5% of households borrowed, used savings or sold assets to defray these costs. More than half (53.1%) of TB affected households experienced TB-related costs above 20% of their annual household expenditure, with the main cost drivers being non-medical expenditure such as travel, nutritional supplements and food. CONCLUSION: Despite free health care in public health facilities, over half of Ugandan TB affected households experience catastrophic costs. Roll out of social protection interventions like TB assistance programs, insurance schemes, and enforcement of legislation related to social protection through multi-sectoral action plans with central NTP involvement would palliate these costs.