Tuberculosis and diabetes mellitus comorbidity in an adult Ugandan population.

BACKGROUND: Diabetes mellitus (DM) has a direct impact on the clinical manifestation and prognosis of active tuberculosis disease (TB) and is known to increase the chance of developing the condition. We sought to determine the prevalence of DM in adult Ugandan patients with recently diagnosed TB and the associated sociodemographic, anthropometric, and metabolic characteristics of TB-DM comorbidity. METHODS: In this cross-sectional study conducted at the adult TB treatment centres of three tertiary healthcare facilities in Uganda, we screened adult participants with recently diagnosed TB (diagnosed in < 2 months) for DM. All participants were screened with five tests; initially with a random blood glucose (RBG) test, and then later with fasting blood glucose (FBG), laboratory-based glycated hemoglobin (HbA1c), point-of-care (POC) HbA1c, and oral glucose tolerance test (OGTT) if the RBG was ≥ 6.1 mmol/l. The WHO guidelines for diagnosing and managing DM were used to support the DM diagnosis. To identify the factors associated with DM-TB comorbidity, logistic regression was used. RESULTS: A total of 232 participants with recently diagnosed TB were screened for DM. Of these, 160 (69%) were female. The median (IQR) age, body mass index, and RBG of all study participants was 35 (27-42) years, 19.2 (17.6-21.3) kg/m2, and 6.1 (5.5-7.2) mmol/l, respectively. About half of the participants (n = 117, 50.4%) had RBG level ≥ 6.1 mmol/l. Of these, 75 (64.1%) participants returned for re-testing. Diabetes mellitus was diagnosed in 32 participants, corresponding to a prevalence of 13.8% (95% CI 9.9-18.9). A new diagnosis of DM was noted in 29 (90.6%) participants. On logistic regression, age ≥ 40 years was associated with increased odds of TB and DM comorbidity (AOR 3.12, 95% CI 1.35-7.23, p = 0.008) while HIV coinfection was protective (AOR 0.27, 95% CI 0.10-0.74, p = 0.01). CONCLUSION: TB and DM comorbidity was relatively common in this study population. Routine screening for DM in adult Ugandan patients with recently diagnosed TB especially among those aged ≥ 40 years and HIV-negative patients should be encouraged in clinical practice.

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.

Prevalence of and characteristics associated with in-hospital mortality in a Ugandan neurology ward.

BACKGROUND: While the burden of neurologic illness in developing countries is increasing, less is known about mortality among patients admitted to sub-Saharan African hospitals with neurologic disease. We sought to characterize the rate and patient-level predictors of in-hospital mortality in a Ugandan Neurology ward.cc. METHODS: Data was prospectively collected on 335 patients admitted to the Neurology ward of Mulago Hospital, Kampala, Uganda. Kaplan-Meier survival curves and multivariate COX proportional hazard modeling were used to assess survival. RESULTS: Within our sample (n = 307), 35.8% received no diagnosis at time of hospital admission. Stroke (27.3%), head trauma (19.6%), and malaria (16.0%) were the most common diagnoses. Among the 56 (18.5%) patients who died during the index hospitalization, the most common diagnosis at admission and at death was stroke. Adjusted regression analysis showed that patients without a diagnosis at time of death (HR = 7.01 [2.42-20.35], p < .001) and those with diagnoses of infections (HR = 5.21 [2.16-12.58], p = <.001), stroke (HR = 2.69 [1.20-6.04], p = .017), or head trauma (HR = 3.39, [1.27-9.07], p = 0.15) had worse survival. CONCLUSIONS: In-hospital mortality affected nearly 20% of the cohort, with worse survival among those without a diagnosis and with infections, stroke, head trauma. Future work should identify reasons for increased mortality among these high-risk groups and implement targeted interventions.

Improving inpatient medication adherence using attendant education in a tertiary care hospital in Uganda.

QUALITY PROBLEM: Although widely utilized in resource-rich health care systems, the use of quality improvement (QI) techniques is less common in resource-limited environments. Uganda is a resource-limited country in Sub-Saharan Africa that faces many challenges with health care delivery. These challenges include understaffing, inconsistent drug availability and inefficient systems that limit the provision of clinical care. INITIAL ASSESSMENT: Poor adherence to prescribed inpatient medications was identified as a key shortcoming of clinical care on the internal medicine wards of Mulago National Referral Hospital, Kampala, Uganda. Baseline data collection revealed a pre-intervention median inpatient medication adherence rate of 46.5% on the study ward. Deficiencies were also identified in attendant (lay caretaker) education, and prescriber and pharmacy metrics. CHOICE OF SOLUTION: A QI team led by a resident doctor and consisting of a QI nurse, a pharmacist and a ward nurse supervisor used standard QI techniques to address this issue. IMPLEMENTATION: Plan-Do-Study-Act cycle interventions focused on attendant involvement and education, physician prescription practices and improving pharmacy communication with clinicians and attendants. EVALUATION: Significant improvements were seen with an increase in overall medication adherence from a pre-intervention baseline median of 46.5% to a post-intervention median of 92%. Attendant education proved to be the most effective intervention, though resource and staffing limitations made institutionalization of these changes difficult. LESSONS LEARNED: QI methods may be the way forward for optimizing health care delivery in resource-limited settings like Uganda. Institutionalization of these methods remains a challenge due to shortage of staff and other resource limitations.

Perceptions of epilepsy among first-year medical students at Mulago Hospital in Kampala, Uganda.

Epilepsy is associated with stigma throughout the world, which leads to poor treatment of people with epilepsy (PWE). In Uganda, there are more than 75,000 PWE and a large treatment gap. This study evaluated the knowledge, attitudes, and practices regarding epilepsy among first-year medical students at Mulago Hospital. A 22-question survey was developed based on the previous studies of Birbeck et al.'s regarding the stigma of epilepsy in Zambia. This was administered to first-year medical students (96 respondents) at Mulago Hospital in Uganda. More than 80% said that they would not allow their children to marry PWE. Most respondents believed that epilepsy was a mental illness, and many believed that PWE cannot have normal intelligence. Students reported that there was a negative perception and negative treatment of PWE in the community. Some students believed that epilepsy was caused by supernatural causes and was contagious. These misperceptions must be identified and corrected among medical students and other healthcare providers to allow for fair treatment of PWE; this should be incorporated into medical school curriculums in Uganda.

Diagnostic accuracy of two confirmatory tests for diabetes mellitus in adult Ugandans with recently diagnosed tuberculosis.

Objective: The optimal confirmatory tests for diabetes mellitus (DM) in patients with tuberculosis (TB) vary across populations. This study aimed to evaluate the performance of two confirmatory tests for DM against the oral glucose tolerance test (OGTT) as the reference test in adult Ugandans with recently diagnosed TB. Methods: A total of 232 adult participants receiving TB treatment underwent initial screening for DM with random blood glucose (RBG) measurement. Participants with a RBG level ⩾6.1 mmol/l received additional screening with fasting blood glucose (FBG), laboratory-measured glycated haemoglobin (HbA1c) and an OGTT. Using the latter as the gold standard and reference test, we evaluated the diagnostic accuracy of laboratory-measured HbA1c and FBG. Results: Of the 232 participants initially screened for DM using RBG measurement, 117 participants (50.4%) had RBG level ⩾6.1 mmol/l and were scheduled to return for additional blood glucose testing. Of these, 75 (64.1%) participants returned for FBG and HbA1c measurements. A diagnosis of DM was made in 32 participants, corresponding to a prevalence of 13.8% [95% CI 9.9-18.9].The areas under the curve (AUC) for FBG and laboratory-measured HbA1c were 0.69 [95% CI 0.47-0.90] and 0.65 [95% CI 0.43-0.87], respectively. The sensitivity and specificity of a FBG level of ⩾7 mmol/l were 57.1% [95% CI 18.4-90.1] and 74.6% [95% CI 62.5-84.5], respectively, whereas the sensitivity and specificity for laboratory-measured HbA1c of ⩾6.5 mmol/l (48 mmol/mol) were 14.3% [95% CI 0.40-57.9] and 95.3% (86.9-99.0%), respectively. Conclusion: FBG may be better than laboratory-measured HbA1c in confirming DM in adult Ugandans with recently diagnosed TB. However, because of the small study sample size, larger studies evaluating the diagnostic utility of these diabetes screening tests in adult Ugandans with TB are needed to confirm these findings.

Appropriate diabetes test in patients with tuberculosis Diabetes mellitus (DM) is a common condition in patients with tuberculosis and proactively screening for the condition is encouraged in all adult patients with tuberculosis. In this study, a total of 232 adult Ugandans with recently diagnosed tuberculosis were screened for DM using random glucose test, fasting blood glucose test, glycated haemoglobin test and an oral glucose tolerance test (OGTT), as the gold-standard and reference test. Compared with the OGTT, a fasting blood glucose test was noted to be a better screening test for diabetes mellitus than glycated haemoglobin in these patients and may be used as a follow-up test to random blood glucose in the screening and diagnosis of DM in adult Ugandans with tuberculosis.

Recurrent pneumothorax in a human immunodeficiency virus-positive patient with multidrug-resistant tuberculosis: a rare case of bronchopleural fistula: a case report.

BACKGROUND: Human immunodeficiency virus/tuberculosis coinfections have amplified the multidrug-resistant tuberculosis pandemic in many countries in Sub-Saharan Africa, and multidrug-resistant tuberculosis has become a major public health threat. There is a paucity of data on severe complications of multidrug-resistant tuberculosis in the context of human immunodeficiency virus coinfection despite the increasing prevalence of multidrug-resistant tuberculosis/human immunodeficiency virus coinfection and the complexity of multidrug-resistant tuberculosis treatment. This report describes a rare case of complicated multidrug-resistant tuberculosis in a human immunodeficiency virus-positive individual. CASE PRESENTATION: A 39-year-old human immunodeficiency virus-positive Ugandan male on anti-retroviral therapy for 6 years, who had recently completed treatment for drug-susceptible tuberculosis from a public hospital, presented to the tuberculosis ward of Mulago National Referral Hospital with worsening respiratory symptoms including persistent cough with purulent sputum, fever, right chest pain, and shortness of breath. On admission, a diagnosis of drug-resistant tuberculosis was made following a positive sputum Xpert MTB/Rif test with rifampicin resistance. Culture-based tuberculosis tests and line probe assay confirmed multidrug-resistant tuberculosis. The patient was given multidrug-resistant tuberculosis treatment that included bedaquiline, isoniazid, prothionamide, clofazimine, ethambutol, levofloxacin, and pyrazinamide and switched to second-line anti-retroviral therapy that included tenofovir/lamivudine/lopinavir/ritonavir. Chest X-ray revealed a hydro-pneumothorax, following which a chest tube was inserted. With persistent bubbling from the chest tube weeks later and a check chest X-ray that showed increasing pleural airspace (pneumothorax) and appearance of a new air-fluid level, chest computed tomography scan was performed, revealing a bronchopleural fistula in the right hemithorax. The computed tomography scan also revealed a pyo-pneumothorax and lung collapse involving the right middle and lower lobes as well as a thick-walled cavity in the right upper lobe. With the pulmonary complications, particularly the recurrent pneumothorax, bronchopleural fistula, and empyema thoracis, cardiothoracic surgeons were involved, who managed the patient conservatively and maintained the chest tube. The patient continued to be ill with recurrent pneumothorax despite the chest tube, until relatives opted for discharge against medical advice. CONCLUSIONS: Complicated human immunodeficiency virus-related multidrug-resistant tuberculosis is not uncommon in settings of high human immunodeficiency virus/tuberculosis prevalence and is often associated with significant morbidity and mortality. Early diagnosis and treatment of multidrug-resistant tuberculosis, with rigorous monitoring for human immunodeficiency virus-positive individuals, is necessary to prevent debilitating complications.

SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in a Child in Uganda: A Paediatric Experience in a Resource-Limited Setting.

SARS-CoV-2-associated Multisystem Inflammatory Syndrome in children (MIS-C) has been described in developed settings that have reported a high burden of COVID-19 cases. However, to date, there are few published cases of MIS-C that have been described in the African region. MIS-C has high morbidity and even mortality without a prompt diagnosis. We report a case of a 9-year-old girl who presented with typical clinical features of MIS-C in Uganda but had a delay in diagnosis. This case report aims to raise awareness among health providers in similar settings to improve clinical suspicion of MIS-C, facilitate prompt diagnosis and treatment, and thus improve outcomes.

Unique circulating microRNA profiles in epidemic Kaposi's sarcoma.

Background: Human herpesvirus 8 (HHV-8) causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS and is the most common HIV-related malignancy worldwide. The lack of a diagnostic assay to detect latent and early-stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based noninvasive biomarker assay for epidemic KS. Methods: This was a comparative cross-sectional study involving 27 patients with epidemic KS and 27 HIV-positive adults with no prior diagnosis or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA were performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyse the sequencing data. Results: Fifteen out of the 27 epidemic KS-positive subjects (55.6%) tested positive for HHV-8 DNA, whereas only 3 (11.1%) out of the 27 HIV-positive, KS-negative subjects tested positive for HHV-8 DNA. Additionally, we found a unique miRNA expression signature in 49 circulating miRNAs in epidemic KS subjects compared to subjects with no epidemic KS, with 41 miRNAs upregulated and 8 miRNAs downregulated. Subjects with latent KS infection had a differential upregulation of circulating miR-193a compared to HIV-positive, KS-negative subjects for whom circulating HHV-8 DNA was not detected. Further analysis of serum from epidemic KS patients revealed a miRNA signature according to KS tumor status and time since first HIV diagnosis. Conclusions: This study reveals unique circulating miRNA profiles in the serum of patients with epidemic KS versus HIV-infected subjects with no KS, as well as in subjects with latent KS. Many of the dysregulated miRNAs in epidemic KS patients were previously reported to have crucial roles in KS infection and latency, highlighting their promising roles as potential biomarkers of latent or active KS infection.

Perceptions of Adolescents and Health Workers Towards Adolescents' TB Diagnosis in Central Uganda: A Cross-Sectional Qualitative Study.

PURPOSE: Prompt diagnosis of TB among adolescents may reduce transmission and improve individual outcomes. However, TB diagnosis in adolescents is challenging. This study sought to understand challenges to adolescent TB diagnosis. METHODS: We conducted qualitative focus group discussions (FGDs) to explore adolescents' and health workers' perspectives on challenges to TB diagnosis among adolescents seeking care at four secondary health care facilities in Uganda. Eight FGDs were conducted: four with 32 adolescents consulting for medical care and four with 34 health workers involved in TB care. RESULTS: Adolescents were aware of TB and associated risk factors and believed behaviours like smoking and alcohol use are risk factors for TB. They reported school schedules limit them from seeking TB care and have to miss school or wait for holidays to seek TB diagnosis. They noted school nurses do not take much interest in diagnosing TB and do not refer them to hospitals for further evaluation when they present with TB symptoms. Furthermore, adolescents reported cross-cutting issues like loss of trust in public health systems, encountering unfriendly, judgmental and uncooperative health workers. Health workers mentioned the school environment exposes adolescents to TB as the dormitories they sleep in are overcrowded. They indicated that it was difficult to make a diagnosis of TB in adolescents as the adolescents do not disclose health information. They reported fellow health workers perceive adolescents as being at low risk of TB as they believe most often adolescents are HIV negative and thus have reduced risk of TB. CONCLUSION: Adolescents present unique challenges that need to be addressed if TB diagnosis is to improve. These challenges could be handled by interventions that lead to minimal disruptions on school schedules, provision of adolescent-friendly services and intervention to build capacity of health care workers in the provision of adolescent-friendly services.

Discordance of the Repeat GeneXpert MTB/RIF Test for Rifampicin Resistance Detection Among Patients Initiating MDR-TB Treatment in Uganda.

BACKGROUND: The Global Laboratory Initiative (GLI) guidelines recommend repeat for GeneXpertMTB/RIF (XpertMTB/RIF) in patients with a low pretest probability of rifampicin resistance (RR). METHODS: This was a cross-sectional study using results of sputum specimens collected from participants screened for the STREAM 2 trial. We recruited all patients with XpertMTB/RIF RR-TB detected who were referred for RR/multidrug-resistant (MDR) TB treatment initiation at Mulago National Referral Hospital, Kampala, between September 2017 and October 2019. At baseline, smear microscopy, repeat XpertMTB/RIF, Xpert Ultra, and MTBDRplus assays were done on sputum specimens. Culture-based drug susceptibility testing (DST) was performed on discordant specimens. We analyzed the prevalence and factors associated with discordance between initial and repeat XpertMTB/RIF RR and false XpertMTB/RIF RR. False XpertMTB/RIF RR was defined as no RR detected by any of Xpert Ultra, LPA, or culture DST (reference comparator). RESULTS: A total of 126/130 patients had repeat XpertMTB/RIF results, of whom 97 (77.0%) had M. tuberculosis detected, 81 (83.5%) had RR detected, and 1 (1.0%) had RR indeterminate. The prevalence of discordant XpertMTB/RIF RR was 15/96 (15.6%), whereas false XpertMTB/RIF RR prevalence was 10/96 (10.4%).Low-bacillary load sputum specimens were more likely to have discordant XpertMTB/RIF RR and false XpertMTB/RIF RR results (adjusted odds ratio [aOR], 0.04; 95% CI, 0.00-0.37; P = .01; aOR, 0.02; 95% CI, 0.01-0.35; P = .01, respectively). CONCLUSIONS: Our findings show a high false-positive rifampicin resistance rate in low-TB burden patients, which calls for repeat testing in order to prevent unnecessary prescription of anti-MDR-TB therapy.

Music and dance in respiratory disease management in Uganda: a qualitative study of patient and healthcare professional perspectives.

INTRODUCTION: Music and dance are increasingly used as adjunctive arts-in-health interventions in high-income settings, with a growing body of research suggesting biopsychosocial benefits. Such low-cost, low-resource interventions may have application in low-resource settings such as Uganda. However, research on perceptions of patients and healthcare professionals regarding such approaches is lacking. METHODS: We delivered sample sessions of music and dance for chronic respiratory disease (CRD) to patients and healthcare professionals. Seven participants took part in one singing and dance sample session. One patient completed only the dance session. We then conducted an exploratory qualitative study using thematic analysis of semistructured interviews with healthcare professionals and patients regarding (1) the role of music and dance in Ugandan life and (2) the perceived acceptability and feasibility of using music and dance in CRD management in Uganda. RESULTS: We interviewed 19 participants, made up of 11 patients with long-term respiratory conditions and 8 healthcare professionals, who were selected by purposeful convenience sampling. Four key themes were identified from interview analysis: music and dance (1) were central components of daily life; (2) had an established role supporting health and well-being; and (3) had strong therapeutic potential in respiratory disease management. The fourth theme was (4) the importance of modulating demographic considerations of culture, religion and age. CONCLUSION: Music and dance are central to life in Uganda, with established roles supporting health and well-being. These roles could be built on in the development of music and dance interventions as adjuncts to established components of CRD disease management like pulmonary rehabilitation. Through consideration of key contextual factors and codevelopment and adaptation of interventions, such approaches are likely to be well received.

Rifampicin susceptibility discordance between Xpert MTB/RIF G4 and Xpert Ultra before MDRT-TB treatment initiation: A case report from Uganda.

Tuberculosis (TB) resistance to rifampicin, the most powerful drug leads to increase in mortality. Globally, half a million new patients develop such resistant TB each year, coupled with both inappropriate diagnosis and treatment initiation. We report a case of rifampicin resistant Mycobacterium tuberculosis whose rifampicin resistance was missed by Xpert MTB/RIF Assay G4 but detected by the Xpert MTB/RIF Ultra assay at different time points leading to increased delays for MDR-TB treatment initiation at Mulago Hospital, Kampala, Uganda. Our case report compels greater urgency in accelerating the transition to the newer assay, Ultra, to benefit from higher sensitivity of rifampicin resistance detection.

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.

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.

Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda.

RATIONALE: Detailed data on the characteristics and outcomes of patients with COVID-19 in sub-Saharan Africa are limited. OBJECTIVE: We determined the clinical characteristics and treatment outcomes of patients diagnosed with COVID-19 in Uganda. MEASUREMENTS: As of the 16 May 2020, a total of 203 cases had been confirmed. We report on the first 56 patients; 29 received hydroxychloroquine (HCQ) and 27 did not. Endpoints included admission to intensive care, mechanical ventilation or death during hospitalisation. MAIN RESULTS: The median age was 34.2 years; 67.9% were male; and 14.6% were <18 years. Up 57.1% of the patients were asymptomatic. The most common symptoms were fever (21.4%), cough (19.6%), rhinorrhea (16.1%), headache (12.5%), muscle ache (7.1%) and fatigue (7.1%). Rates of comorbidities were 10.7% (pre-existing hypertension), 10.7% (diabetes) and 7.1% (HIV), Body Mass Index (BMI) of ≥30 36.6%. 37.0% had a blood pressure (BP) of >130/90 mm Hg, and 27.8% had BP of >140/90 mm Hg. Laboratory derangements were leucopenia (10.6%), lymphopenia (11.1%) and thrombocytopenia (26.3%). Abnormal chest X-ray was observed in 14.3%. No patients reached the primary endpoint. Time to clinical recovery was shorter among patients who received HCQ, but this difference did not reach statistical significance. CONCLUSION: Most of the patients with COVID-19 presented with mild disease and exhibited a clinical trajectory not similar to other countries. Outcomes did not differ by HCQ treatment status in line with other concluded studies on the benefit of using HCQ in the treatment of COVID-19.

Trends of admissions and case fatality rates among medical in-patients at a tertiary hospital in Uganda; A four-year retrospective study.

BACKGROUND: Sub-Saharan Africa suffers from a dual burden of infectious and non-communicable diseases. There is limited data on causes and trends of admission and death among patients on the medical wards. Understanding the major drivers of morbidity and mortality would help inform health systems improvements. We determined the causes and trends of admission and mortality among patients admitted to Mulago Hospital, Kampala, Uganda. METHODS AND RESULTS: The medical record data base of patients admitted to Mulago Hospital adult medical wards from January 2011 to December 2014 were queried. A detailed history, physical examination and investigations were completed to confirm the diagnosis and identify comorbidities. Any histopathologic diagnoses were made by hematoxylin and eosin tissue staining. We identified the 10 commonest causes of hospitalization, and used Poisson regression to generate annual percentage change to describe the trends in causes of hospitalization. Survival was calculated from the date of admission to the date of death or date of discharge. Cox survival analysis was used to identify factors associate with in-hospital mortality. We used a statistical significance level of p<0.05. A total of 50,624 patients were hospitalized with a median age of 38 (range 13-122) years and 51.7% females. Majority of patients (72%) had an NCD condition as the primary reason for admission. Specific leading causes of morbidity were HIV/AIDS in 30% patients, hypertension in 14%, tuberculosis (TB) in 12%), non-TB pneumonia in11%) and heart failure in 9.3%. There was decline in the proportion of hospitalization due to malaria, TB and pneumonia with an annual percentage change (apc) of -20% to -6% (all p<0.03) with an increase in proportions of admissions due to chronic kidney disease, hypertension, stroke and cancer, with apc 13.4% to 24%(p<0.001). Overall, 8,637(17.1%) died during hospitalization with the highest case fatality rates from non-TB pneumonia (28.8%), TB (27.1%), stroke (26.8%), cancer (26.1%) and HIV/AIDS (25%). HIV-status, age above 50yrs and being male were associated with increased risk of death among patients with infections. CONCLUSION: Admissions and case fatality rates for both infectious and non-infectious diseases were high, with declining trends in infectious diseases and a rising trend in NCDs. Health care systems in sub-Saharan region need to prepare to deal with dual burden of disease.

High prevalence of hypertension and cardiovascular disease risk factors among medical students at Makerere University College of Health Sciences, Kampala, Uganda.

BACKGROUND: Cardiovascular disease has become a leading global health challenge representing the largest cause of mortality in adults worldwide. Non communicable diseases are neglected in Uganda over infectious diseases. With increased urbanization, there is likely increase in burden of these NCDs yet there is paucity of reliable data regarding the NCD burden. We assessed the prevalence of hypertension and other cardiovascular disease risk factors among medical students at Makerere University, College of Health Sciences in Kampala, Uganda. METHODS: We conducted a cross-sectional study at Makerere University comprising 180 medical students. We used a standardized questionnaire and anthropometric measurements to assess their cardiovascular disease risk factors using JNC-7. Logistic regression was used to assess factors associated with elevated blood pressure. RESULTS: Of the 180 students surveyed, 107 (59%) were males, mean age was 22 years (SD = 3 years), and 159 (88%) were in their preclinical years of training. Cardiovascular risk factors with the highest prevalence were alcohol consumption (31.7%); elevated systolic blood pressure (14%); and excessive salt intake (13%). Participants with elevated systolic blood pressure were more likely to be older (OR = 1.18), overweight (OR = 1.08), and with a personal history of cardiovascular disease (OR = 4.68). CONCLUSIONS: The prevalence of hypertension and known cardiovascular disease risk factors is high among the medical students. Strategies to prevent cardiovascular disease among the young population should be put in place.