Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma.

Background: To 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. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This 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. Results: Overall, 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 <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.

Re-estimation of the burden of serious fungal diseases in Uganda.

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.

How common are serious fungal infections in Uganda? Why was the study done? This study was conducted to provide an updated understanding of the occurrence and impact of serious fungal diseases in Uganda. The aim was to monitor changes in the epidemiology of fungal diseases related to shifts in the at-risk population or the availability of local data. What did the researchers do? Utilizing the Leading International Fungal Education methodology, the research team systematically reviewed published data on fungal diseases in Uganda. In instances where Ugandan data was unavailable, regional, or global data were incorporated. This method allowed for a thorough examination of the incidence and prevalence of various serious fungal diseases, considering the local context. What did the researchers find? With a population of approximately 45 million, the study estimated that nearly 9% of Ugandans, totalling around 4,099,357 individuals, are affected by serious fungal diseases annually. Notable findings include the prevalence of recurrent Candida vaginitis, oral candidiasis, and oesophageal candidiasis in HIV-infected individuals. Cryptococcal meningitis and Pneumocystis pneumonia were identified as significant contributors, along with various aspergillosis syndromes and widespread cases of tinea capitis. What do the findings mean? These findings underscore the substantial impact of serious fungal diseases on the health of almost 9% of the Ugandan population each year. Recognizing tuberculosis and HIV as major predisposing factors, the study calls for urgent interventions to prevent, diagnose, and treat these diseases effectively. The identified targets, including improved access to essential antifungal medications, training of health care workers on fungal diseases, and increasing access to essential diagnostics. These interventions can significantly contribute to improving public health outcomes in Uganda.

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.

Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda.

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.

Challenges to Implementation of Community Health Worker-Led Chronic Obstructive Pulmonary Disease (COPD) Screening and Referral in Rural Uganda: A Qualitative Study using the Implementation Outcomes Framework.

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. The burden of COPD is expected to increase in low- and middle-income countries (LMICs). COPD screening and diagnostics tools are often inaccessible in rural settings of LMICs. To contribute to the growing body of evidence on the effectiveness of Community Health Worker (CHW) interventions, this study aims to understand the facilitators and barriers of implementing a CHW-led COPD screening and referral program in rural Uganda. Methods: This qualitative study was conducted from September to October 2022 to explore Community Members, CHWs, and Healthcare Providers (HCPs) perceptions on the challenges of CHW-delivered COPD programming in Nakaseke, rural Uganda. In total, we held eight individual in-depth interviews with CHWs, ten in-depth interviews with HCPs and six focus group discussions with 34 Community Members. Research assistants audio-recorded and transcribed interviews verbatim. The implementation outcomes framework guided the thematic analysis. Results: Implementation acceptability was constrained by a lack of COPD awareness, a lack of perceived utility in COPD screening as well as stigma around the diagnostic process. Limited spirometry adoption was also attributed to Community Member accessibility and willingness to participate in the COPD diagnostic referral process. The high patient volume and the complex, time-consuming diagnostic and referral process hindered successful implementation. To enhance program sustainability, all participants suggested increasing CHW support, medication access, decentralizing COPD care and upscaling follow-up of Community Members by CHWs. Conclusion: CHW-led interventions remain a potentially critical tool to alleviate barriers to treatment and self-management in settings where access to care is limited. While community-based interventions can create sustainable infrastructure to improve health outcomes, formative assessments of the potential barriers prior to intervention are required. Evidence-based, localized approaches and sustained funding are imperative to achieve this.

Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda.

Background: We evaluated the effect of mixed-MTB strain infection on the performance of Line Probe Assay (LPA) and GeneXpert MTB/RIF (Xpert) assays among patients initiating MDR-TB treatment in Uganda. Methods: This was a cross-sectional study using 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 the 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 males 3/33 (9.7%) and among middle-aged adults, 4/30 (13.3%). Lineage 4 of MTB contributed 3/33 (9.1%) 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.

Serum E-selectin and endothelial cell-specific Molecule-1 levels among people living with HIV on long term ART in Uganda: a pilot cross-sectional study.

BACKGROUND: Prolonged exposure to HIV and anti-retroviral therapy (ART) has been linked with endothelial cell activation which subsequently predisposes people living with HIV (PLWH) to cardiovascular diseases. Serum biomarkers of endothelial cell activation such as E-Selectin and endothelial cell-specific molecule-1 (ESM-1) could aid in early detection of PLWH at a risk of cardiovascular diseases. However, there is a paucity of data on these biomarkers like E-selectin and endothelial cell-specific molecule-1 (ESM-1) among PLWH on long term ART (≥ 10 years) in Uganda. The aim of this study is to determine the serum levels of these biomarkers in this population. METHODS: This was a cross-sectional study where we randomly sampled 73 stored serum samples of PLWH who were enrolled in the Infectious Diseases Institute (IDI) ART long term (ALT cohort). We measured serum levels of E-selectin and ESM-1 by ELISA. Data was summarized using median and interquartile range. Inferential statistics were performed to determine predictors of elevated levels of E-selectin. RESULTS: Of the 73 samples analyzed, 38 (52.1%) were from female participants. The mean age was 54 ± 9.0 years. Twenty participants (27.4%) had a history of smoking while 52 (71.2%) had a history of alcohol intake. Twenty-five (34.3%) of the participants were overweight whereas 4 (5.6%) were obese. Fifty-four (74%) had an undetectable viral load (≤ 0 copies/ml) and the mean duration of ART at the time of sampling (2014/2015) was 10.4 ± 0.4 years. While serum levels of ESM-1 were not detectable in any of our samples, the median E-selectin levels was 147.6 µm/L ranging from 8.44 µm/L and 1,979.36 µm/L. Sixty-seven participants (91.8%) had elevated levels of E-selectin (> 39 µm/L). CD4 count > 500 cells/µl compared to lower counts was a predictor of elevated levels of E-Selectin (adjusted Odd Ratio 12.5, 95% CI (1.03 - 149.95, p < 0.05). CONCLUSIONS: The majority (91.8%) of PLWH on long term ART had elevated levels of E-selectin. Having high CD4 count (> 500 cells/µl) was predictive of elevated levels of E-Selectin. Future work should longitudinally assess the trend of levels of E-selectin and ESM-1 while assessing for cardiovascular diseases endpoint.

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.

Review of electrocardiographic abnormalities among people living with HIV in Sub-Saharan Africa: A systematic review.

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.

Respiratory Support Techniques for COVID-19-Related ARDS in a Sub-Saharan African Country: A Multicenter Observational Study.

BACKGROUND: Limited data from low-income countries report on respiratory support techniques in COVID-19-associated ARDS. RESEARCH QUESTION: Which respiratory support techniques are used in patients with COVID-19-associated ARDS in Uganda? STUDY DESIGN AND METHODS: A multicenter, prospective, observational study was conducted at 13 Ugandan hospitals during the pandemic and included adults with COVID-19-associated ARDS. Patient characteristics, clinical and laboratory data, initial and most advanced respiratory support techniques, and 28-day mortality were recorded. Standard tests, log-rank tests, and logistic regression analyses were used for statistical analyses. RESULTS: Four hundred ninety-nine patients with COVID-19-associated ARDS (mild, n = 137; moderate, n = 247; and severe, n = 115) were included (ICU admission, 38.9%). Standard oxygen therapy (SOX), high-flow nasal oxygen (HFNO), CPAP, noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) was used as the first-line (most advanced) respiratory support technique in 37.3% (35.3%), 10% (9.4%), 11.6% (4.8%), 23.4% (14.4%), and 17.6% (36.6%) of patients, respectively. The first-line respiratory support technique was escalated in 19.8% of patients. Twenty-eight-day mortality was 51.9% (mild ARDS, 13.1%; moderate ARDS, 62.3%; severe ARDS, 75.7%; P < .001) and was associated with respiratory support techniques as follows: SOX, 19.9%; HFNO, 31.9%; CPAP, 58.3%; NIV 61.1%; and IMV, 83.9% (P < .001). Proning was used in 79 patients (15.8%; 59 of 79 awake) and was associated with lower mortality (40.5% vs 54%; P = .03). The oxygen saturation to Fio2 ratio (OR, 0.99; 95% CI, 0.98-0.99; P < .001) and respiratory rate (OR, 1.07; 95% CI, 1.03-1.12; P = .002) at admission and NIV (OR, 6.31; 95% CI, 2.29-17.37; P < .001) or IMV (OR, 8.08; 95% CI, 3.52-18.57; P < .001) use were independent risk factors for death. INTERPRETATION: SOX, HFNO, CPAP, NIV, and IMV were used as respiratory support techniques in patients with COVID-19-associated ARDS in Uganda. Although these data are observational, they suggest that the use of SOX and HFNO therapy as well as awake proning are associated with a lower mortality resulting from COVID-19-associated ARDS in a resource-limited setting.

Tracing Makerere University's 100 years' contribution to lung science/medicine.

Dear Editor, African Health Sciences Journal, This year, 2022, Makerere University will be celebrating 100 years of existence. As current lung science/medicine experts, we felt it as important to trace the University's contribution to lung science and medicine. In this letter, we trace and describe some of the early work done by Makerere University/Mulago Hospital affiliated scientists, identify prominent players in lung science over the 100 years, and present the university's scholarly contribution to this field, as available in online databases. We include both Makerere University and Mulago Hospital affiliated scientists, because for many years, staff of these two institutions have worked together in teaching, research and patient care.

Effectiveness of a community health worker-delivered care intervention for hypertension control in Uganda: study protocol for a stepped wedge, cluster randomized control trial.

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.

Aspergillus-specific IgM/IgG antibody serostatus of patients hospitalized with moderate-critical COVID-19 in Uganda.

Invasive pulmonary aspergillosis is known to complicate the coronavirus diseases-2019 (COVID-19), especially those with critical illness. We investigated the baseline anti-Aspergillus antibody serostatus of patients with moderate-critical COVID-19 hospitalized at 3 COVID-19 Treatment Units in Uganda. All 46 tested patients, mean age 30, and 11% with underlying respiratory disease had a negative serum anti-Aspergillus IgM/IgG antibody immunochromatographic test on day 3 (mean) of symptom onset (range 1-26), but follow up specimens to assess seroconversion were not available.

Aspergillus-specific IgM/IgG antibody serostatus of patients hospitalized with moderate-critical COVID-19 in Uganda

Invasive pulmonary aspergillosis is known to complicate the coronavirus diseases-2019 (COVID-19), especially those with critical illness. We investigated the baseline anti Aspergillus antibody serostatus of patients with moderate-critical COVID-19 hospitalized at 3 COVID-19 Treatment Units in Uganda. All 46 tested patients, mean age 30, and 11% with underlying respiratory disease had a negative serum anti-Aspergillus IgM/IgG antibody immunochromatographic test on day 3 (mean) of symptom onset (range 1-26), but follow up specimens to assess seroconversion were not available

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.

Strategies for the prevention, diagnosis and treatment of COPD in low- and middle- income countries: the importance of primary care.

INTRODUCTION: Low- and middle-income countries (LMICs) bear a high proportion of the global morbidity and mortality caused by COPD. Increased exposure to risk factors throughout life (e.g. malnutrition, indoor and outdoor air pollution, and smoking) is associated with higher COPD prevalence in LMICs and the lack of treatment availability increases avoidable harm. AREAS COVERED: This review covers the epidemiology and burden of COPD in LMICs, and challenges and recommendations related to health-care systems, prevention, diagnosis, and treatment. Main challenges are related to under-resourced health-care systems (such as limited availability of spirometry, rehabilitation, and medicines). Lack of policy and practical local guidelines on COPD diagnosis and management further contribute to the low diagnostic and treatment rates. In the absence of, or limited number of respiratory specialists, primary care practitioners (general practitioners, nurses, pharmacists, physiotherapists, and community health workers) play an even more pivotal role in COPD management in LMICs. EXPERT OPINION: Raising awareness on COPD, educating health-care workers, patients, and communities on cost-effective preventive measures as well as improving availability, affordability and proper use of diagnostic and pharmacological and non-pharmacologic treatment in primary care are the key interventions needed to improve COPD prevention, diagnosis, and care in LMICs.

Prevalence of Aspergillus fumigatus skin positivity in adults without an apparent/known atopic disease in Uganda.

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.

Study protocol for a randomised controlled trial assessing the impact of pulmonary rehabilitation on maximal exercise capacity for adults living with post-TB lung disease: Global RECHARGE Uganda.

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.

Chronic obstructive pulmonary disease prevalence and associated factors in an urban HIV clinic in a low income country.

INTRODUCTION: In 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 FINDINGS: HIV-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/FVC<0.7). We determined its prevalence and association with demographic characteristics, body mass index (BMI) and known risk factors. Of 288 participants enrolled, 177 (61%) were female; 253 (88%) were from urban residences, median age was 45 years (IQR: 39-51), 71(25%) were 'ever' smokers, 284(99%) reported biomass fuel use and 72(25%) had a history of tuberculosis. All except 1 participant were on antiretroviral therapy, median current CD4 (cells/mm3) was 558 (IQR 402-753) and 275(96%) were virologically suppressed. Nearly half (130/288, 45%) had recurrent respiratory symptoms. The prevalence of COPD was 3.1% (9/288) [95% CI: 1.63-5.92]. COPD was associated with: previous tuberculosis, (adjusted odds ratio (AOR): 6.36, [95% CI 1.64-35.84], P = 0.036), self-reported chronic shortness of breath (AOR: 9.06, [95% CI 1.34-61.10], P = 0.024) and a BMI <21 Kg/m2 (AOR: 10.42 [95% CI: 1.61-100.00], P = 0.013). CONCLUSION: In this HIV population, COPD prevalence was low and was associated with previous tuberculosis, self-reported chronic shortness of breath and BMI <21 Kg/m2.