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Abstract Background Pulmonary complications are common among children with sickle cell disease (SCD). However, there is little literature on associated lung function abnormalities in Uganda. We aimed to determine the prevalence, patterns, and factors associated with abnormal lung function among children with SCD in a tertiary care hospital in Uganda. Method A cross-sectional study was conducted among children aged 6 to 18 years at the SCD clinic (SCC) of Mulago National Super-Specialized Hospital between January 2020 and April 2021. Data on sociodemographic and clinical characteristics was collected using a standardized questionnaire. Laboratory investigations, including a complete blood count and serum lactate dehydrogenase (LDH), were done. Spirometry was performed following the ATS/ERS standards. Multivariable modified Poisson regression analysis was performed to determine factors associated with abnormal lung function. Results A total of 332 participants were enrolled. The mean age was 11.7 ± 3.4 years, and 184 (55.4%) were female. Overall, 126 (37.9%) participants had abnormal lung function: 67/126 (53.2%) restrictive, 57/126 (45.2%) obstructive, and 2/126 (1.6%) mixed-ventilatory patterns. Factors associated with abnormal lung function were; serum LDH level > 600UL (aIRR: 1.89 95% CI: 1.2 — 7.4, p = 0.049), a history of acute chest syndrome (aIRR: 1.55, 95% CI: 1.06–2.25, p = 0.024), wasting (aIRR: 1.33, 95%CI: 1.02 — 1.72, p = 0.032), and use of charcoal for household cooking (aIRR: 1.49, 95% CI: 1.03–2.15, p = 0.035). Conclusion More than one-third of children with SCD in Uganda have lung function abnormalities. Strategies to improve nutrition, reduce exposure to charcoal smoke, and monitoring serum LDH levels may be important in preventing or managing abnormal lung function in this population. The identification of reversible and irreversible airway obstruction in children with sickle cell disease also highlights the need for targeted interventions to address these specific patterns of abnormal lung function.

Abstract The FRESHAIR4Life study aims to reduce the non-communicable disease (NCD) burden by implementing preventive interventions targeting adolescents’ exposure to tobacco use and air pollution (AP) worldwide. This paper presents the FRESHAIR4Life methodology and initial rapid review results. The rapid review, using various databases and PubMed, aimed to guide decision-making on risk factor focus, target areas, and populations. It showed variable NCD mortality rates related to tobacco use and AP across the participating countries, with tobacco as the main risk factor in the Kyrgyz Republic, Greece, and Romania, and AP prevailing in Pakistan and Uganda. Adolescent exposure levels, sources, and correlates varied. The study will continue with an in-depth situational analysis to guide the selection, adaptation, and integration of evidence-based interventions into the FRESHAIR4Life prevention package. This package will be implemented, evaluated, assessed for cost-effectiveness, and iteratively refined. The research places a strong emphasis on co-creation, capacity building, and comprehensive communication and dissemination.

Abstract Background Mixed M. tuberculosis (MTB) infection occurs when one is infected with more than one clonally distinct MTB strain. This form of infection can assist MTB strains to acquire additional mutations, facilitate the spread of drug-resistant strains, and boost the rate of treatment failure. Hence, the presence of mixed MTB infection could affect the performance of some rapid molecular diagnostic tests such as Line Probe Assay (LPA) and GeneXpert MTB/RIF (Xpert) assays. Methods This was a cross-sectional study that used sputum specimens collected from participants screened for STREAM 2 clinical trial between October 2017 and October 2019. Samples from 62 MTB smear-positive patients and rifampicin-resistant patients from peripheral health facilities were processed for Xpert and LPA as screening tests for eligibility in the trial. From November 2020, processed stored sputum samples were retrieved and genotyped to determine the presence of mixed-MTB strain infection using a standard 24-locus Mycobacterial Interspersed Repetitive Unit–Variable Number Tandem-Repeat (MIRU-VNTR). Samples with at least 20/24 MIRU-VNTR loci amplified were considered for analysis. Agar proportional Drug Susceptibility Test (DST) was performed on culture isolates of samples that had discordant results between LPA and Xpert. The impact of the presence of mixed-MTB strain on Xpert and LPA test interpretation was analyzed. Results A total of 53/62 (85%) samples had analyzable results from MIRU-VNTR. The overall prevalence of mixed-MTB infection was 5/53 (9.4%). The prevalence was highest among male’s 3/31 (9.7%) and among middle-aged adults, 4/30 (33.3%). Lineage 4 of MTB contributed 3/5 (60.0%) of the mixed-MTB infection prevalence. Having mixed MTB strain infection increased the odds of false susceptible Xpert test results (OR 7.556, 95% CI 0.88–64.44) but not for LPA. Being HIV-positive (P = 0.04) independently predicted the presence of mixed MTB infection. Conclusions The presence of mixed-MTB strain infection may affect the performance of the GeneXpert test but not for LPA. For patients with high pre-test probability of rifampicin resistance, an alternative rapid method such as LPA should be considered.

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.

BackgroundTo date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.AimTo elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.MethodsThis was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.ResultsOverall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and

Background: It is of utmost importance to monitor any change in the epidemiology of fungal diseases that may arise from a change in the number of the at-risk population or the availability of local data. Objective: We sought to update the 2015 publication on the incidence and prevalence of serious fungal diseases in Uganda. Methods: Using the Leading International Fungal Education methodology, we reviewed published data on fungal diseases and drivers of fungal diseases in Uganda. Regional or global data were used where there were no Ugandan data. Results: With a population of ~45 million, we estimate the annual burden of serious fungal diseases at 4,099,357 cases (about 9%). We estimated the burden of candidiasis as follows: recurrent Candida vaginitis (656,340 cases), oral candidiasis (29,057 cases), and esophageal candidiasis (74,686 cases) in HIV-infected people. Cryptococcal meningitis annual incidence is estimated at 5553 cases, Pneumocystis pneumonia at 4604 cases in adults and 2100 cases in children. For aspergillosis syndromes, invasive aspergillosis annual incidence (3607 cases), chronic pulmonary aspergillosis (26,765 annual cases and 63,574 5-year-period prevalent cases), and prevalence of allergic bronchopulmonary aspergillosis at 75,931 cases, and severe asthma with fungal sensitization at 100,228 cases. Tinea capitis is common with 3,047,989 prevalent cases. For other mycoses, we estimate the annual incidence of histoplasmosis to be 646 cases and mucormycosis at 9 cases. Conclusion: Serious fungal diseases affect nearly 9% of Ugandans every year. Tuberculosis and HIV remain the most important predisposition to acute fungal infection necessitating accelerated preventive, diagnostic, and therapeutic interventions for the management of these diseases.

Abstract Background Over 80% of the morbidity and mortality related to non-communicable diseases (NCDs) occurs in low-income and middle-income countries (LMICs). Community health workers (CHWs) may improve disease control and medication adherence among patients with NCDs in LMICs, particularly in sub-Saharan African settings. In Uganda, and the majority of LMICs, management of uncontrolled hypertension remains limited in constrained health systems. Intervening at the primary care level, using CHWs to improve medical treatment outcomes has not been well studied. We aim to determine the effectiveness of a CHW-led intervention in blood pressure control among confirmed hypertensive patients and patient-related factors associated with uncontrolled hypertension. Methods We will conduct a stepped-wedge cluster randomized controlled trial study of 869 adult patients with hypertension attending two NCD clinics to test the effectiveness, acceptability, and fidelity of a CHW-led intervention. The multi-component intervention will be centered on monthly household visits by trained CHWs for a period of 1 year, consisting of the following: (1) blood pressure and sugar monitoring, (2) BMI monitoring, (3) cardiovascular disease risk assessment, (4) using checklists to guide monitoring and referral to clinics, and (5) healthy lifestyle counseling and education. During home visits, CHWs will remind patients of follow-up visits. We will measure blood pressure at baseline and 3-monthly for the entire cohort. We will conduct individual-level mixed effects analyses of study data, adjusting for time and clustering by patient and community. Conclusion The results of this study will inform community delivered HTN management across a range of LMIC settings. Trial registration ClinicalTrials.gov NCT05068505 . Registered on October 6, 2021.

Introduction Electrocardiographic (ECG) abnormalities are increasingly being reported among people living with HIV (PLWH). However, the exact prevalence of ECG abnormalities among PLWH in Sub-Saharan Africa (SSA), a region with one of the highest burdens of HIV, is not known. Through a systematic review, we determined the prevalence and patterns of ECG abnormalities among PLWH in SSA. Methods We conducted a search in online databases including EMBASE, MEDLINE, CINAHL and Research for Life for studies published between 1st January 2000 and 31st December 2020. Studies reporting any form of ECG abnormalities published in English were screened and reviewed for eligibility. Retrieved studies were assessed for validity using the modified Newcastle-Ottawa Scale. Data was summarized qualitatively, and ECG abnormalities were further subcategorized into rate, conduction, and rhythm abnormalities as well as atrial and ventricular enlargements. Results We retrieved seventeen of the 219 studies assessed for eligibility published between 2001 and 2020, with a total of 2,572 eligible participants. The mean age of the participants ranged between 6.8 years and 58.6 years. Of the 17 studies, 8 (47%) were case-control, 6 (35.3%) cross-sectional and 3 (17.6%) were cohort in design. Thirteen studies were conducted in the adult population while four were conducted in the pediatric population. The prevalence of ECG abnormalities ranged from 10% to 81% and 6.7% to 26.5% in the adult and pediatric population respectively. Among studies done in the adult population, conduction abnormalities were the most reported (9 studies) with a prevalence ranging from 3.4% to 53.5%. In the pediatric population, rate abnormalities were the most reported (4 studies) with a prevalence ranging from 3.9% to 20.9%. The heterogeneity in results could be attributed to the absence of uniform criteria to define ECG abnormalities. Conclusion Our findings highlight a high prevalence of ECG abnormalities among PLWH in SSA. Consideration of ECG in the comprehensive evaluation of cardiac dysfunction among PLWH in SSA maybe warranted.

Abstract Background Diagnosis of chronic pulmonary aspergillosis (CPA) is based on a combination of clinical symptomatology, compatible chest imaging findings, evidence of Aspergillus infection and exclusion of alternative diagnosis, all occurring for more than 3 months. Recently, a rapid, highly sensitive and specific point-of-care lateral flow device (LFD) has been introduced for the detection of Aspergillus-specific immunoglobulin (Ig)G, especially in resource-limited settings where CPA is underdiagnosed and often misdiagnosed as smear-negative pulmonary tuberculosis (PTB). Therefore, in our setting, where tuberculosis (TB) is endemic, exclusion of PTB is an important first step to the diagnosis of CPA. We used the recently published CPA diagnostic criteria for resource-limited settings to identify patients with CPA in our center. Case presentation Three Ugandan women (45/human immunodeficiency virus (HIV) negative, 53/HIV infected and 18/HIV negative), with a longstanding history of cough, chest pain, weight loss and constitutional symptoms, were clinically and radiologically diagnosed with PTB and empirically treated with an anti-tuberculous regimen despite negative microbiological tests. Repeat sputum Mycobacteria GeneXpert assays were negative for all three patients. On further evaluation, all three patients met the CPA diagnostic criteria with demonstrable thick-walled cavities and fungal balls (aspergilomas) on chest imaging and positive Aspergillus-specific IgG/IgM antibody tests. After CPA diagnosis, anti-TB drugs were safely discontinued for all patients, and they were initiated on capsules of itraconazole 200 mg twice daily with good treatment outcomes. Conclusions The availability of simple clinical diagnostic criteria for CPA and a LFD have the potential to reduce misdiagnosis of CPA and in turn improve treatment outcomes in resource-limited settings.

Abstract Background Respiratory diseases are among the leading causes of morbidity and mortality in Uganda, but there is little attention and capacity for management of chronic respiratory diseases in the health programmes. This survey assessed gaps in knowledge and skills among healthcare workers in managing respiratory illnesses. Methods A cross sectional study was conducted among primary care health workers, specialist physicians and healthcare planners to assess gaps in knowledge and skills and, training needs in managing respiratory illnesses. The perspectives of patients with respiratory diseases were also sought. Data were collected using questionnaires, patient panel discussions and review of pre-service training curricula for clinicians and nurses. Survey Monkey was used to collect data and descriptive statistical analysis was undertaken for quantitative data, while thematic content analysis techniques were utilized to analyze qualitative data. Results A total of 104 respondents participated in the survey and of these, 76.9% (80/104) were primary care health workers, 16.3% (17/104) specialist clinicians and 6.7% (7/104) healthcare planners. Over 90% of the respondents indicated that more than half of the patients in their clinics presented with respiratory symptoms. More than half (52%) of the primary care health workers were not comfortable in managing chronic respiratory diseases like asthma and COPD. Only 4% of them were comfortable performing procedures like pulse oximetry, nebulization, and interpreting x-rays. Majority (75%) of the primary care health workers had received in-service training but only 4% of the sessions focused on respiratory diseases. The pre-service training curricula included a wide scope of respiratory diseases, but the actual training had not sufficiently prepared health workers to manage respiratory diseases. The patients were unsatisfied with the care in primary care and reported that they were often treated for the wrong illnesses. Conclusions Respiratory illnesses contribute significantly to the burden of diseases in primary care facilities in Uganda. Management of patients with respiratory diseases remains a challenge partially because of inadequate knowledge and skills of the primary care health workers. A training programme to improve the competences of health workers in respiratory medicine is highly recommended.

Background: Skin prick testing (SPT) is an important investigation in the evaluation of allergy to fungal pathogens. However, the background sensitivity to fungal allergens among healthy people in Uganda is unknown. Our aim was to assess the background prevalence of Aspergillus fumigatus SPT positivity in apparently healthy adults without known atopic disease in Uganda. Methods: For this pilot study, we recruited 50 healthy volunteers using convenience sampling, 56% of whom were health workers. We performed the SPT for A. fumigatus according to manufacturer’s instructions. A wheal diameter of ⩾3 mm was considered positive. Results: The prevalence of A. fumigatus skin positivity was 60% (30/50). Participants with a positive A. fumigatus SPT were significantly younger than those with a negative result [median age (years): 28 versus 35; p = 0.005]. Conclusion: There is a high skin positivity against A. fumigatus among non-atopic healthy Ugandan adults. There is an urgent need to establish a normal wheal cut-off value for this population. SPT alone may be an unreliable test for the diagnosis of A. fumigatus associated allergic syndromes. More studies are needed to define the prevalence of A. fumigatus skin positivity among non-atopic healthy population in Africa.

Introduction The burden of post-tuberculosis (TB) lung disease (PTBLD) is steadily increasing in sub-Saharan Africa, causing disability among TB survivors. Without effective medicines, the mainstay of PTBLD treatment evolves around disease prevention and supportive treatment. Pulmonary rehabilitation (PR), a low-cost, non-pharmacological intervention has shown effectiveness in a group of PTBLD individuals but has not been tested in a clinical trial. This study aims to assess the impact of a 6-week PR programme on maximal exercise capacity and other outcomes among adults in Uganda living with PTBLD.Methods and analysis This is a randomised waiting-list controlled trial with blinded outcome measures, comparing PR versus usual care for patients with PTBLD. A total of 114 participants will be randomised (1:1) to receive either usual care (on the waiting list) or PR, with follow-up assessments at 6 weeks and 12 weeks postintervention. The primary outcome is change in walking distance measured by the Incremental Shuttle Walk Test from baseline to the end of 6 weeks of PR. All secondary outcomes will be compared between the PR and usual care arms from baseline to 6-week and 12-week follow-ups. Secondary outcomes include self-reported respiratory symptoms, physical activity, psychological well-being, health-related quality of life and cost–benefit analysis. All randomised participants will be included in the intention-to-treat analysis population. The primary efficacy analysis will be based on both per-protocol and modified intention-to-treat populations.Ethics and dissemination The trial has received ethical clearance from the Mulago Hospital Research and Ethics Committee (MHREC 1478), Kampala, Uganda as well as the Uganda National Council for Science and Technology (SS 5105). Ethical approval has been obtained from the University of Leicester, UK research ethics committee (Ref No. 22349). Study findings will be published in appropriate peer-reviewed journals and disseminated at appropriate local, regional and international scientific meetings and conferences.Trial registration number ISRCTN18256843.Protocol version Version 1.0 July 2019.

Background: Immunization is an important strategy for controlling the COVID-19 pandemic. COVID-19 vaccination was recently launched in Uganda, with prioritization to healthcare workers and high-risk individuals. In this study, we aimed to determine the acceptability of COVID-19 vaccine among persons at high risk of COVID-19 morbidity and mortality in Uganda. Methods: Between 29 March and 14 April 2021, we conducted a cross-sectional survey consecutively recruiting persons at high risk of severe COVID-19 (diabetes mellitus, HIV and cardiovascular disease) attending Kiruddu National Referral Hospital outpatient clinics. A trained research nurse administered a semi-structured questionnaire assessing demographics, COVID-19 vaccine related attitudes and acceptability. Descriptive statistics, bivariate and multivariable analyses were performed using STATA 16. Results: A total of 317 participants with a mean age 51.5 ± 14.1 years were recruited. Of this, 184 (60.5%) were female. Overall, 216 (70.1%) participants were willing to accept the COVID-19 vaccine. The odds of willingness to accept COVID-19 vaccination were four times greater if a participant was male compared with if a participant was female [adjusted odds ratio (AOR): 4.1, 95% confidence interval (CI): 1.8–9.4, p = 0.00]. Participants who agreed (AOR: 0.04, 95% CI: 0.01–0.38, p = 0.003) or strongly agreed (AOR: 0.04, 95% CI: 0.01–0.59, p = 0.005) that they have some immunity against COVID-19 were also significantly less likely to accept the vaccine. Participants who had a history of vaccination hesitancy for their children were also significantly less likely to accept the COVID-19 vaccine (AOR: 0.1, 95% CI: 0.01–0.58, p = 0.016). Conclusion: The willingness to receive a COVID-19 vaccine in this group of high-risk individuals was comparable to the global COVID-19 vaccine acceptance rate. Increased sensitization, myth busting and utilization of opinion leaders to encourage vaccine acceptability is recommended.

Background: The burden of asthma in Africa is high, and yet the disease is not universally prioritised. Data on allergic asthma and its impact on asthma morbidity are limited in Africa. Our aim was to describe the distribution of skin prick positivity among asthmatics in Eastern Africa. Methods: From August 2016 to May 2018, 1671 asthmatic patients were enrolled from Uganda, Kenya, and Ethiopia as part of the African Severe Asthma Program clinical study. Skin prick testing was performed at baseline using a panel of 12 allergens, and factors associated with skin prick reactivity determined. Results: Of the 1, 671 patients recruited, 71% were female with a median age of 40 years, 93.6% were aged >15 years and the patterns of asthma symptom frequency was intermittent in 2.9%, mild persistent in 19.9%, moderate persistent in 42.6% and severe persistent in 34.6% at baseline. Self-reported triggers, were dust (92%), cold weather (89%), upper respiratory infections (84%), strong smells (79%) and exposure to tobacco (78%). The majority (90%) of the participants had at least 1 positive allergen reaction, with 0.9% participants reacting to all the 12 allergens. Participants commonly reacted to house dust mites (66%), Blomia tropicalis (62%), and the German cockroach (52%). Patients sensitized to more allergens (>2) had significantly reduced lung function (FEV ≤ 80%; p = 0.001) and were more likely to visit the emergency department due to asthma (p = 0.012). There was no significant relationship between number of allergens and measures of asthma control, quality of life, and other clinical outcomes. Only the country of origin was independently associated with atopy among African asthmatics. Conclusion: There is a high prevalence of skin prick positivity among East African patients with asthma, with the commonest allergen being house dust mite. Skin reactivity did not correlate well with asthma severity and poor asthma control. The relation between atopy, measured through skin prick testing, and measures of asthma control among asthma patients in Eastern Africa is unclear and needs further study. Trial registration: The ASAP study was registered prospectively. ClinicalTrials.gov Identifier: NCT03065920; Registration date: February 28, 2017; Last verified: February 28, 2017.

Abstract Background Recent large-scale population data on the prevalence of asthma and its risk factors are lacking in Uganda. This survey was conducted to address this data gap. Methods A general population based survey was conducted among people ≥12 years. A questionnaire was used to collect participants socio-demographics, respiratory symptoms, medical history, and known asthma risk factors. Participants who reported wheeze in the past 12 months, a physician diagnosis of asthma or current use of asthma medications were classified as having asthma. Asthmatics who were ≥ 35 years underwent spirometry to determine how many had fixed airflow obstruction (i.e. post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio

Abstract Background HIV and asthma are highly prevalent diseases in Africa but few studies have assessed the impact of HIV on asthma prevalence in high HIV burden settings. The objective of this analysis was to compare the prevalence of asthma among persons living with HIV (PLHIV) and those without HIV participating in the Uganda National Asthma Survey (UNAS). Methods UNAS was a population-based survey of persons aged ≥12 years. Asthma was diagnosed based on either self-reported current wheeze concurrently or within the prior 12 months; physician diagnosis; or use of asthma medication. HIV was defined based on confidential self-report. We used Poisson regression with robust standard errors to estimate asthma prevalence and the prevalence ratio (PR) for HIV and asthma. Results Of 3416 participants, 2067 (60.5%) knew their HIV status and 103 (5.0%) were PLHIV. Asthma prevalence was 15.5% among PLHIV and 9.1% among those without HIV, PR 1.72, (95%CI 1.07–2.75, p = 0.025). HIV modified the association of asthma with the following factors, PLHIV vs. not PLHIV: tobacco smoking (12% vs. 8%, p =

Cor pulmonale is a rare complication of pulmonary aspergillosis (CPA). A 45-year-old Ugandan male with a history of recurrent community-acquired pneumonias was admitted with symptoms of progressive difficulty in breathing, chronic productive cough, non-exertional left sided chest pain and progressive weight loss occurring over a 12-month period. Chest CT scan and echocardiography confirmed the diagnosis of CPA with an aspergilloma complicating bronchiectasis, complicated with cor pulmonale. However, this was previously clinically misdiagnosed as PTB. Keywords: Chronic pulmonary aspergillosis, Cor pulmonale, Recurrent community acquired pneumonia, Itraconazole, 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.

IntroductionIn the last decade, survival of people living with HIV (PLHIV) has dramatically increased due wide availability of effective antiretroviral therapy. However, PLHIV remain at a comparatively higher risk of non-communicable comorbidities. We sought to determine the burden of COPD and its associations in an urban tertiary HIV clinic in Uganda.Methods and findingsHIV-infected adults attending the Makerere University Joint AIDS program; aged ≥30 years without acute ailments were screened for COPD using study questionnaires and spirometry (post-bronchodilator FEV1/FVCConclusionIn this HIV population, COPD prevalence was low and was associated with previous tuberculosis, self-reported chronic shortness of breath and BMI

BackgroundDiagnosis of fungal allergies in asthma remains problematic in low-and middle-income countries due to non-availability of point-of-care testing. In this study, we aimed to evaluate the performance of an Aspergillus immunochromatographic technology (ICT) IgG/M lateral flow device (LFD) for the serological diagnosis of allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) among Ugandan adult asthmatics.Methods374 adult (aged ≥18years) asthmatics in the African Severe Asthma Program study, Ugandan site constituted the study population. ABPA and SAFS were diagnosed according to standard criteria. Asthmatics who did not meet the above criteria constituted a control group. The LFD tests were performed and read according to manufacturer's instructions.ResultsABPA was found in 12/374 (3.2%) and SAFS in 60/374 (16%) participants. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the Aspergillus ICT for the diagnosis of ABPA were 0.0%, 96.4%, 0.0% and 96.7% respectively, and for SAFS 6.7%, 97.1%, 30.8% and 84.5% respectively. False positive and negative rates were 3.5% and 3.2% for ABPA and 2.4% and 14.9% for SAFS, respectively. Patients with a positive LFD significantly had higher median Aspergillus fumigatus-specific IgE levels compared to those with negative LFD (median: 0.06 kUA/l VS 0.03 kUA/L, P = 0.011).ConclusionThe Aspergillus ICT IgG/M LFD had a poor diagnostic performance for the diagnosis of both ABPA and SAFS. Its greatest value may be in distinguishing chronic and allergic aspergillosis in Africa.

Objectives There is growing recognition around the importance of multimorbidity in low-income and middle-income country (LMIC) settings, and specifically the need for pragmatic intervention studies to reduce the risk of developing multimorbidity, and of mitigating the complications and progression of multimorbidity in LMICs. One of many challenges in completing such research has been the selection of appropriate outcomes measures. A 2018 Delphi exercise to develop a core-outcome set for multimorbidity research did not specifically address the challenges of multimorbidity in LMICs where the global burden is greatest, patterns of disease often differ and health systems are frequently fragmented. We, therefore, aimed to summarise and critically review outcome measures suitable for studies investigating mitigation of multimorbidity in LMIC settings.Setting LMIC.Participants People with multimorbidity.Outcome measures Identification of all outcome measures.Results We present a critical review of outcome measures across eight domains: mortality, quality of life, function, health economics, healthcare access and utilisation, treatment burden, measures of ‘Healthy Living’ and self-efficacy and social functioning.Conclusions Studies in multimorbidity are necessarily diverse and thus different outcome measures will be appropriate for different study designs. Presenting the diversity of outcome measures across domains should provide a useful summary for researchers, encourage the use of multiple domains in multimorbidity research, and provoke debate and progress in the field.

BackgroundDetermining mycobacterial burden is important in assessing severity of disease, evaluating infectiousness and predicting patient treatment outcomes. Mycobacterial burden assessed by smear microscopy grade and time to culture positivity is clearly interpretable by most physicians. GeneXpert (Xpert) has been recommended by WHO as a first line tuberculosis (TB) diagnostic test as an alternative to smear microscopy. Xpert gives cycle threshold (Ct) values as a potential measure for mycobacterial burden. For physicians to clearly interpret Ct values as measures of mycobacterial burden, this study compared the Xpert quantification capabilities with those of smear microscopy and culture. The study also determined a linear relationship between Xpert Ct values and MGIT culture time to positivity (MGIT-TTP) and associated factors. A cut off Ct value which best predicts smear positivity was also determined using the Receiver Operator Curve analysis method.ResultsExcluding missing results and rifampicin resistant TB cases, a moderately strong correlation of 0.55 between Xpert Ct value and smear grade was obtained. A weak correlation of 0.37 was obtained between Xpert Ct values and MGIT time to positivity while that between Xpert Ct values and LJ culture was 0.34. The Xpert Ct values were found to increase by 2.57 for every unit increase in days to positive and HIV status was significantly associated with this relationship. A cut off Ct value of 23.62 was found to best predict smear positivity regardless of HIV status.ConclusionOur study findings show that GeneXpert Ct values are comparable to smear microscopy as a measure of M. tuberculosis burden and can be used to replace smear microscopy. However, given the low correlation between Xpert Ct value and culture positivity, Xpert Ct values cannot replace culture as a measure of M. tuberculosis burden among TB patients.

BackgroundAsthma is one of the neglected diseases in Africa with a high prevalence. Allergic fungal diseases have been reported to complicate asthma progression and treatment outcomes. However, data about fungal asthma and its associated complications are limited in Africa. We aimed to estimate the burden of fungal asthma among adults and children in Africa using a systematic review.MethodsWe first engaged the Institute for Health Metrics and Evaluation (IHME) to highlight the trend in morbidity and mortality attributed to asthma in Africa. We then searched PubMed, HINARI and Google Scholar for all studies of any design focusing on fungal asthma in any African country. Languages were restricted to English and French, but not year of publication. We estimated the weighted prevalence of allergic fungal infections among asthmatics with a 95% CI and pooled the results using a random effects model. This study is registered with PROSPERO, number CRD42019117319.ResultsThe IHME data showed that there has been a gradual increase in morbidity and mortality due to asthma in African adults with a prevalence of 4%. Our search retrieved 5233 citations. We retained 20 studies that met our selection criteria. These were from 13 African countries published between 1967 and 2018. There were eight cross-sectional studies and twelve review articles. The average asthma prevalence in Africa was 6% from these studies. The prevalence of fungal sensitisation was relatively high (3-52%) in the asthmatic population with an average of 28% and a pooled estimate of 23.3%, mostly due to Aspergillus species. Prevalence of Allergic bronchopulmonary apsergillosis was estimated at 1.6-21.2%. Diagnosis of fungal allergy was mostly made by skin prick tests. There was no data on the use of medication to manage fungal asthma. None of the studies evaluated the association between fungal allergy and asthma severity. Data were lacking in children.ConclusionThere is a high prevalence of fungal sensitization among Africans with asthma. Fungal asthma is a significant problem in Africa but there remains a paucity of data on the epidemiology and associated complications. There is urgent need for national epidemiological studies to estimate the actual burden of fungal asthma in Africa.

Background Tuberculosis (TB) patients who smoke tobacco are at an increased risk for adverse TB treatment outcomes. The association between smoking and TB is well known but has not yet received sufficient attention in terms of TB care standards in Uganda. This study describes prevalence of smoking among presumptive TB patients and risk factors associated with presumptive TB among tobacco smokers in Uganda. Methods This was a national cross-sectional population-based study among respondents aged 15 years and above. We defined a presumptive TB patient as any person with cough (≥14 days) and abnormal chest x-ray.We collected information on current and past tobacco use, socio-economic and demographic status using structured interviewer-administered questionnaires. Data analysis entailed descriptive statistics, followed by multivariate logistic regression with backward elimination, adjusted for clustering by facility. Results Detailed interviews were conducted for 45294 individuals; prevalence of presumptive TB was 11.8% (95% CI =11.5-12.1), 12.7% (95% CI=12.4-13.0) had a history of tobacco smoking (both previous and current tobacco smokers). Prevalence of current tobacco smoking was 7.3% (95% CI=7.1-7.6) and prevalence of past tobacco smoking was 7.1% (CI= 6.9-7.4). History of tobacco smoking among presumptive TB patients was 26.7% (95% CI=25.5-27.9), presumptive TB among current tobacco smokers was 13.7% (95% CI=12.8-14.7) while for past tobacco smokers was 15.0% (95% CI=14.0-16.0). Not having any education AOR (Adjusted odds ratio) 2.90 (95% CI=2.34-3.6), primary education OR 1.47 (95% CI=1.22-1.76) and being male AOR 8.6 (95% CI=7.3-10.2) were the key risk factors for history of smoking among TB patients. Conclusions Tobacco smoking was associated with presumptive TB in Ugandans. Smoking cessation interventions should be included in the current TB care standards at various levels of the TB health care system In Uganda.

The existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce delays in TB diagnosis in HIV-infected smear-negative presumptive TB. We sought to determine predictors for MTB culture-positivity among these patients.This study was nested into a prospective evaluation of HIV-infected outpatients and inpatients clinically suspected to have TB who were screened by smear-microscopy on two spot sputum samples. Data on socio-demographics, clinical symptoms, antiretroviral therapy, CXR, CD4 count, mycobacterial sputum and blood cultures and TB-LAM were collected. Logistic regression and conditional inference tree analysis were used to determine the most predictive indicators for MTB culture-positivity.Of the 418 smear-negative participants [female, 64%; median age (IQR) 32 (28-39) years, median CD4 106 (IQR 22 - 298) cells/mm3], 96/418 (23%) were sputum and/ or blood culture-positive for Mycobacterium tuberculosis (MTB) complex. Abnormal CXR (aOR 3.68, 95% CI 1.76- 7.71, p=0.001) and positive urine TB-LAM (aOR 6.21, 95% CI 3.14-12.27, p< 0.001) were significantly associated with MTB culture-positivity. Previous TB treatment (aOR 0.41, 95% CI 0.17-0.99, p=0.049) reduced the likelihood of a positive MTB culture. A conditional inference tree analysis showed that positive urine TB-LAM and abnormal CXR were the most predictive indicators of MTB culture-positivity. A combination of urine TB-LAM test and CXR had sensitivity and specificity of 50% and 86.1% respectively overall, and 70.8% and 84.1% respectively among those with CD4

BACKGROUND:In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS:Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION:Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART.

Diagnosis of pleural tuberculosis (TB) using routinely available diagnostic methods is challenging due to the paucibacillary nature of the disease. Histopathology and pleural tissue TB culture involves an invasive procedure which requires expertise and appropriate equipment, both often unavailable in many health units. Xpert MTB/Rif test has been widely evaluated in sputum specimens but data on its performance in pleural TB is scarce. We evaluated the accuracy of Cepheid's Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural TB in Uganda.Consenting adult patients with exudative pleural effusions underwent pleural biopsy and the tissue obtained subjected to Lowenstein-Jensen and mycobacterial growth indicator tube MTB cultures and histopathology. Pleural fluid for Xpert MTB/Rif testing was also collected. Data on socio-demographic characteristics, clinical symptoms, HIV status and CD4 count were also collected. Sensitivity, specificity, positive and negative predictive values of Xpert MTB/Rif test on pleural fluid in pleural TB diagnosis were calculated using pleural tissue MTB culture and/or histopathology as the reference standard.Of the 116 participants [female 50%, mean age 34 (SD ±13], 87/116 (75%) had pleural TB confirmed on pleural tissue culture and/or histopathology. The Xpert MTB/Rif test identified 25 (28.7%) of the 87 confirmed pleural TB cases. The sensitivity and specificity of Xpert MTB/Rif test were 28.7% and 96.6% respectively while the positive and negative predictive values were 96.1% and 31.1% respectively.Xpert MTB/Rif test on pleural fluid does not accurately diagnose pleural TB and therefore cannot be used as an initial evaluation test in patients with suspected pleural TB. New, rapid and accurate tests for the diagnosis of pleural TB are still warranted.