Community tuberculosis screening, testing and care, Uganda.

Objective: To assess the effectiveness of a community-based tuberculosis and leprosy intervention in which village health teams and health workers conduct door-to-door tuberculosis screening, targeted screenings and contact tracing. Methods: We conducted a before-and-after implementation study in Uganda to assess the effectiveness of the community tuberculosis intervention by looking at reach, outputs, adoption and effectiveness of the intervention. Campaign 1 was conducted in March 2022 and campaign 2 in September 2022. We calculated percentages of targets achieved and compared case notification rates during the intervention with corresponding quarters in the previous year. We also assessed the leprosy screening. Findings: Over 5 days, campaign 1 screened 1 289 213 people (2.9% of the general population), of whom 179 144 (13.9%) fulfilled the presumptive tuberculosis criteria, and 4043 (2.3%) were diagnosed with bacteriologically-confirmed tuberculosis; 3710 (91.8%) individuals were linked to care. In campaign 2, 5 134 056 people (11.6% of the general population) were screened, detecting 428 444 (8.3%) presumptive tuberculosis patients and 8121 (1.9%) bacteriologically-confirmed tuberculosis patients; 5942 individuals (87.1%) were linked to care. The case notification rate increased from 48.1 to 59.5 per 100 000 population in campaign 1, with a case notification rate ratio of 1.24 (95% confidence interval, CI: 1.22-1.26). In campaign 2, the case notification rate increased from 45.0 to 71.6 per 100 000 population, with a case notification rate ratio of 1.59 (95% CI: 1.56-1.62). Of the 176 patients identified with leprosy, 137 (77.8%) initiated treatment. Conclusion: This community tuberculosis screening initiative is effective. However, continuous monitoring and adaptations are needed to overcome context-specific implementation challenges.

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.

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.

Chronic Obstructive Pulmonary Disease Self-Management in Three Low- and Middle-Income Countries: A Pilot Randomized Trial.

Objectives: Chronic obstructive pulmonary disease (COPD) disproportionately affects low- and middle-income countries. Health systems are ill prepared to manage the increase in COPD cases. Methods: We performed a pilot effectiveness-implementation randomized field trial of a community health worker (CHW)-supported, 1-year self-management intervention in individuals with COPD grades B-D. The study took place in low-resource settings of Nepal, Peru, and Uganda. The primary outcome was the St. George's Respiratory Questionnaire (SGRQ) score at 1 year. We evaluated differences in moderate to severe exacerbations, all-cause hospitalizations, and the EuroQol score (EQ-5D-3 L) at 12 months. Measurements and Main Results: We randomly assigned 239 participants (119 control arm, 120 intervention arm) with grades B-D COPD to a multicomponent, CHW-supported intervention or standard of care and COPD education. Twenty-five participants (21%) died or were lost to follow-up in the control arm compared with 11 (9%) in the intervention arm. At 12 months, there was no difference in mean total SGRQ score between the intervention and control arms (34.7 vs. 34.0 points; adjusted mean difference, 1.0; 95% confidence interval, -4.2, 6.1; P = 0.71). The intervention arm had a higher proportion of hospitalizations than the control arm (10% vs. 5.2%; adjusted odds ratio, 2.2; 95% confidence interval, 0.8, 7.5; P = 0.15) at 12 months. Conclusions: A CHW-based intervention to support self-management of acute exacerbations of COPD in three resource-poor settings did not result in differences in SGRQ scores at 1 year. Fidelity was high, and intervention engagement was moderate. Although these results cannot differentiate between a failed intervention or implementation, they nonetheless suggest that we need to revisit our strategy. Clinical trial registered with www.clinicaltrials.gov (NCT03359915).

Unmet Diagnostic and Therapeutic Opportunities for Chronic Obstructive Pulmonary Disease in Low- and Middle-Income Countries.

Rationale: Chronic obstructive pulmonary disease (COPD) is a prevalent and burdensome condition in low- and middle-income countries (LMICs). Challenges to better care include more effective diagnosis and access to affordable interventions. There are no previous reports describing therapeutic needs of populations with COPD in LMICs who were identified through screening. Objectives: To describe unmet therapeutic need in screening-detected COPD in LMIC settings. Methods: We compared interventions recommended by the international Global Initiative for Chronic Obstructive Lung Disease COPD strategy document, with that received in 1,000 people with COPD identified by population screening at three LMIC sites in Nepal, Peru, and Uganda. We calculated costs using data on the availability and affordability of medicines. Measurement and Main Results: The greatest unmet need for nonpharmacological interventions was for education and vaccinations (applicable to all), pulmonary rehabilitation (49%), smoking cessation (30%), and advice on biomass smoke exposure (26%). Ninety-five percent of the cases were previously undiagnosed, and few were receiving therapy (4.5% had short-acting ß-agonists). Only three of 47 people (6%) with a previous COPD diagnosis had access to drugs consistent with recommendations. None of those with more severe COPD were accessing appropriate maintenance inhalers. Even when available, maintenance treatments were unaffordable, with 30 days of treatment costing more than a low-skilled worker's daily average wage. Conclusions: We found a significant missed opportunity to reduce the burden of COPD in LMIC settings, with most cases undiagnosed. Although there is unmet need in developing novel therapies, in LMICs where the burden is greatest, better diagnosis combined with access to affordable interventions could translate to immediate benefit.

Evaluation of two short standardised regimens for the treatment of rifampicin-resistant tuberculosis (STREAM stage 2): an open-label, multicentre, randomised, non-inferiority trial.

BACKGROUND: The STREAM stage 1 trial showed that a 9-month regimen for the treatment of rifampicin-resistant tuberculosis was non-inferior to the 20-month 2011 WHO-recommended regimen. In STREAM stage 2, we aimed to compare two bedaquiline-containing regimens with the 9-month STREAM stage 1 regimen. METHODS: We did a randomised, phase 3, non-inferiority trial in 13 hospital clinics in seven countries, in individuals aged 15 years or older with rifampicin-resistant tuberculosis without fluoroquinolone or aminoglycoside resistance. Participants were randomly assigned 1:2:2:2 to the 2011 WHO regimen (terminated early), a 9-month control regimen, a 9-month oral regimen with bedaquiline (primary comparison), or a 6-month regimen with bedaquiline and 8 weeks of second-line injectable. Randomisations were stratified by site, HIV status, and CD4 count. Participants and clinicians were aware of treatment-group assignments, but laboratory staff were masked. The primary outcome was favourable status (negative cultures for Mycobacterium tuberculosis without a preceding unfavourable outcome) at 76 weeks; any death, bacteriological failure or recurrence, and major treatment change were considered unfavourable outcomes. All comparisons used groups of participants randomly assigned concurrently. For non-inferiority to be shown, the upper boundary of the 95% CI should be less than 10% in both modified intention-to-treat (mITT) and per-protocol analyses, with prespecified tests for superiority done if non-inferiority was shown. This trial is registered with ISRCTN, ISRCTN18148631. FINDINGS: Between March 28, 2016, and Jan 28, 2020, 1436 participants were screened and 588 were randomly assigned. Of 517 participants in the mITT population, 133 (71%) of 187 on the control regimen and 162 (83%) of 196 on the oral regimen had a favourable outcome: a difference of 11·0% (95% CI 2·9-19·0), adjusted for HIV status and randomisation protocol (p<0·0001 for non-inferiority). By 76 weeks, 108 (53%) of 202 participants on the control regimen and 106 (50%) of 211 allocated to the oral regimen had an adverse event of grade 3 or 4; five (2%) participants on the control regimen and seven (3%) on the oral regimen had died. Hearing loss (Brock grade 3 or 4) was more frequent in participants on the control regimen than in those on the oral regimen (18 [9%] vs four [2%], p=0·0015). Of 134 participants in the mITT population who were allocated to the 6-month regimen, 122 (91%) had a favourable outcome compared with 87 (69%) of 127 participants randomly assigned concurrently to the control regimen (adjusted difference 22·2%, 95% CI 13·1-31·2); six (4%) of 143 participants on the 6-month regimen had grade 3 or 4 hearing loss. INTERPRETATION: Both bedaquiline-containing regimens, a 9-month oral regimen and a 6-month regimen with 8 weeks of second-line injectable, had superior efficacy compared with a 9-month injectable-containing regimen, with fewer cases of hearing loss. FUNDING: USAID and Janssen Research & Development.

Early culture conversion is a poor marker of treatment outcome among people with HIV and drug-resistant TB.

OBJECTIVE: Our objective was to determine associations between early (≤2 months) culture conversion (ECC) among people with HIV and drug-resistant tuberculosis (DRTB) in Uganda. METHODS: This was a countrywide retrospective cohort of people with bacteriologically confirmed DRTB and a positive baseline culture at 16 centres in Uganda between 2013 and 2019. Data were abstracted from treatment files and unit DRTB registers. Monthly sputum cultures were performed using the Lowenstein-Jensen solid medium. RESULTS: We included 664 people with DRTB and a positive baseline culture, of whom 353 (53.4%) also had HIV. Among those living with HIV, 225 (63.7%) were male and 331 (94.3%) were on antiretroviral therapy. The median month of culture conversion was 2 (interquartile range [IQR] 1-3). ECC was observed among 226 people living with HIV (64.0%; 95% confidence interval [CI] 58.9-68.9). A DRTB treatment regimen of six or more drugs was associated with ECC among people living with HIV (adjusted odds ratio [aOR]  3.82; 95% CI 1.06-13.82; p = 0.041). Cure and overall treatment success was observed among 232 (65.7%) and 269 (76.2%) people living with HIV, respectively. However, ECC was not associated with cure (crude odds ratio [OR]  0.97; 95% CI 0.61-1.54; p = 0.901), death (OR 1.12; 95% CI 0.61-2.29; p = 0.610), or overall treatment success (OR 1.29; 95% CI 0.78-2.13; p = 0.326). CONCLUSION: The majority of people living with HIV and DRTB achieve ECC. However, ECC does not predict cure, death, or treatment success. Moreover, it may require six or more drugs to achieve ECC. ECC is not an excellent indicator of the effectiveness of DRTB regimens among people living with HIV.

Implementation of evidence-based multiple focus integrated intensified TB screening to end TB (EXIT-TB) package in East Africa: a qualitative study.

INTRODUCTION: Tuberculosis (TB) remains a major cause of morbidity and mortality, especially in sub-Saharan Africa. We qualitatively evaluated the implementation of an Evidence-Based Multiple Focus Integrated Intensified TB Screening package (EXIT-TB) in the East African region, aimed at increasing TB case detection and number of patients receiving care. OBJECTIVE: We present the accounts of participants from Tanzania, Kenya, Uganda, and Ethiopia regarding the implementation of EXIT-TB, and suggestions for scaling up. METHODS: A qualitative descriptive design was used to gather insights from purposefully selected healthcare workers, community health workers, and other stakeholders. A total of 27, 13, 14, and 19 in-depth interviews were conducted in Tanzania, Kenya, Uganda, and Ethiopia respectively. Data were transcribed and translated simultaneously and then thematically analysed. RESULTS: The EXIT-TB project was described to contribute to increased TB case detection, improved detection of Multidrug-resistant TB patients, reduced delays and waiting time for diagnosis, raised the index of TB suspicion, and improved decision-making among HCWs. The attributes of TB case detection were: (i) free X-ray screening services; (ii) integrating TB case-finding activities in other clinics such as Reproductive and Child Health clinics (RCH), and diabetic clinics; (iii), engagement of CHWs, policymakers, and ministry level program managers; (iv) enhanced community awareness and linkage of clients; (v) cooperation between HCWs and CHWs, (vi) improved screening infrastructure, (vii) the adoption of the new simplified screening criteria and (viii) training of implementers. The supply-side challenges encountered ranged from disorganized care, limited space, the COVID-19 pandemic, inadequate human resources, inadequate knowledge and expertise, stock out of supplies, delayed maintenance of equipment, to absence of X-ray and GeneXpert machines in some facilities. The demand side challenges ranged from delayed care seeking, inadequate awareness, negative beliefs, fears towards screening, to financial challenges. Suggestions for scaling up ranged from improving service delivery, access to diagnostic equipment and supplies, and infrastructure, to addressing client fears and stigma. CONCLUSION: The EXIT-TB package appears to have contributed towards increasing TB case detection and reducing delays in TB treatment in the study settings. Addressing the challenges identified is needed to maximize the impact of the EXIT-TB intervention.

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.

Previous tuberculosis disease as a risk factor for chronic obstructive pulmonary disease: a cross-sectional analysis of multicountry, population-based studies.

BACKGROUND: Risk factors for COPD in high-income settings are well understood; however, less attention has been paid to contributors of COPD in low-income and middle-income countries (LMICs) such as pulmonary tuberculosis. We sought to study the association between previous tuberculosis disease and COPD by using pooled population-based cross-sectional data in 13 geographically diverse, low-resource settings. METHODS: We pooled six cohorts in 13 different LMIC settings, 6 countries and 3 continents to study the relationship between self-reported previous tuberculosis disease and lung function outcomes including COPD (defined as a postbronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) below the lower limit of normal). Multivariable regressions with random effects were used to examine the association between previous tuberculosis disease and lung function outcomes. RESULTS: We analysed data for 12 396 participants (median age 54.0 years, 51.5% male); 332 (2.7%) of the participants had previous tuberculosis disease. Overall prevalence of COPD was 8.8% (range 1.7%-15.5% across sites). COPD was four times more common among those with previous tuberculosis disease (25.7% vs 8.3% without previous tuberculosis disease, p<0.001). The adjusted odds of having COPD was 3.78 times higher (95% CI 2.87 to 4.98) for participants with previous tuberculosis disease than those without a history of tuberculosis disease. The attributable fraction of COPD due to previous tuberculosis disease in the study sample was 6.9% (95% CI 4.8% to 9.6%). Participants with previous tuberculosis disease also had lower prebronchodilator Z-scores for FEV1 (-0.70, 95% CI -0.84 to -0.55), FVC (-0.44, 95% CI -0.59 to -0.29) and the FEV1:FVC ratio (-0.63, 95% CI -0.76 to -0.51) when compared with those without previous tuberculosis disease. CONCLUSIONS: Previous tuberculosis disease is a significant and under-recognised risk factor for COPD and poor lung function in LMICs. Better tuberculosis control will also likely reduce the global burden of COPD.

Discriminative Accuracy of Chronic Obstructive Pulmonary Disease Screening Instruments in 3 Low- and Middle-Income Country Settings.

Importance: Most of the global morbidity and mortality in chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries (LMICs), with significant economic effects. Objective: To assess the discriminative accuracy of 3 instruments using questionnaires and peak expiratory flow (PEF) to screen for COPD in 3 LMIC settings. Design, Setting, and Participants: A cross-sectional analysis of discriminative accuracy, conducted between January 2018 and March 2020 in semiurban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda, using a random age- and sex-stratified sample of the population 40 years or older. Exposures: Three screening tools, the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE; range, 0-6; high risk indicated by a score of 5 or more or score 2-5 with low PEF [<250 L/min for females and <350 L/min for males]), the COPD in LMICs Assessment questionnaire (COLA-6; range, 0-5; high risk indicated by a score of 4 or more), and the Lung Function Questionnaire (LFQ; range, 0-25; high risk indicated by a score of 18 or less) were assessed against a reference standard diagnosis of COPD using quality-assured postbronchodilator spirometry. CAPTURE and COLA-6 include a measure of PEF. Main Outcomes and Measures: The primary outcome was discriminative accuracy of the tools in identifying COPD as measured by area under receiver operating characteristic curves (AUCs) with 95% CIs. Secondary outcomes included sensitivity, specificity, positive predictive value, and negative predictive value. Results: Among 10 709 adults who consented to participate in the study (mean age, 56.3 years (SD, 11.7); 50% female), 35% had ever smoked, and 30% were currently exposed to biomass smoke. The unweighted prevalence of COPD at the 3 sites was 18.2% (642/3534 participants) in Nepal, 2.7% (97/3550) in Peru, and 7.4% (264/3580) in Uganda. Among 1000 COPD cases, 49.3% had clinically important disease (Global Initiative for Chronic Obstructive Lung Disease classification B-D), 16.4% had severe or very severe airflow obstruction (forced expiratory volume in 1 second <50% predicted), and 95.3% of cases were previously undiagnosed. The AUC for the screening instruments ranged from 0.717 (95% CI, 0.677-0.774) for LFQ in Peru to 0.791 (95% CI, 0.770-0.809) for COLA-6 in Nepal. The sensitivity ranged from 34.8% (95% CI, 25.3%-45.2%) for COLA-6 in Nepal to 64.2% (95% CI, 60.3%-67.9%) for CAPTURE in Nepal. The mean time to administer the instruments was 7.6 minutes (SD 1.11), and data completeness was 99.5%. Conclusions and Relevance: This study demonstrated that screening instruments for COPD were feasible to administer in 3 low- and middle-income settings. Further research is needed to assess instrument performance in other low- and middle-income settings and to determine whether implementation is associated with improved clinical outcomes.

Deriving personalised physical activity intensity thresholds by merging accelerometry with field-based walking tests: Implications for pulmonary rehabilitation.

During pulmonary rehabilitation (PR), patients receive individually tailored walking exercise training. The personalised nature of exercise prescription is a fundamental component of PR. Despite this, the measurement of physical activity (PA) has been limited to a 'one size fits all' approach and can be challenging to translate into clinically meaningful or real-world units, such as cadence. This discrepancy may partly explain the inconsistent evidence for the impact of PR on PA. It may also provide an opportunity to standardise PA assessment in the context of chronic respiratory disease (CRD) and PR, where field-based walking tests are routine measures. This technical note provides an example of how to develop personalised PA intensity thresholds, calibrated against an individual's performance on the Incremental Shuttle Walking Test (ISWT; maximal) and Endurance Shuttle Walk Test (ESWT; sub-maximal). These are externally paced tests, with each level (speed) of the tests denoting a specific speed (intensity); ranging 1.8 km/h (ISWT Level 1) to 8.5 km/h (ISWT Level 12). From the ESWT, it becomes possible to evaluate adherence to each individual's walking exercise prescription. Future research should explore this approach and its responsiveness to PR. It may be possible to extend this methodology with the inclusion of physiological parameters (e.g., heart rate, calorimetry, and oxygen consumption) to derive relative intensity markers (e.g. moderate-to-vigorous), accounting for individual differences in exercise capacity, under the same paradigm as PR exercise prescription.

Fungal asthma among Ugandan adult asthmatics.

Fungal sensitization is associated with poor asthma control. We aimed to determine the prevalence and factors associated with fungal asthma among Ugandan adults. Individuals aged ≥18 years with a new diagnosis of asthma in the last 12 months participating in the African Severe Asthma Program constituted the study population. Skin prick test results, clinical and demographic data were retrieved from the database, and serum Aspergillus fumigatus specific antibodies and total IgE were measured in stored blood. We enrolled 374 patients, median (IQR) age 34 (25-45) years, 286 (76.5%) females and 286 (76.5%) with severe asthma. Prevalence of Aspergillus fumigatus sensitization was 42.0% (95% CI: 37.1-47.0%), allergic bronchopulmonary aspergillosis (ABPA) 3.2% (1.8-5.5%), severe asthma with fungal sensitization (SAFS) 16% (12.7-20.1%) and allergic bronchopulmonary mycosis (ABPM) 2.9% (1.7-5.2%). Older age (55-64 years) (crude odds ratio (cOR) = 2.6), sensitization to at least one allergen (cOR = 9.38) and hypertension (cOR = 1.99) were significantly associated with Aspergillus sensitization, whereas tertiary education level (cOR = 0.29), severe depression (cOR = 0.15) and strong emotions (cOR = 0.47) were not. High occupational exposure to Aspergillus (cOR = 4.26) and contact with moulds (cOR = 14.28) were significantly associated with ABPA. Palpitations (cOR = 5.54), uncontrolled asthma (cOR = 3.54), eczema/dermatitis (cOR = 3.07), poor lung function (cOR = 2.11) and frequent exacerbations (cOR = 1.01) were significantly associated with SAFS. Eczema/dermatitis (cOR = 1.55) was significantly associated with ABPM, but cold weather trigger (cOR = 0.24) was not. Fungal asthma is a significant problem among Ugandans with asthma and should be particularly considered in individuals who remain uncontrolled despite optimal standard of care for asthma, as it is responsive to available and affordable oral antifungal therapy. LAY SUMMARY: This study showed that fungal asthma is a significant problem among Ugandans with asthma with a high prevalence. Fungal asthma should be considered in patients with uncontrolled asthma despite receiving optimal standard of care. This is the first modern attempt to define these endotypes of asthma in Africa.

Adoption of evidence-informed guidelines in prescribing protease inhibitors for HIV-Tuberculosis co-infected patients on rifampicin and effects on HIV treatment outcomes in Uganda.

BACKGROUND: We aimed to determine how emerging evidence over the past decade informed how Ugandan HIV clinicians prescribed protease inhibitors (PIs) in HIV patients on rifampicin-based tuberculosis (TB) treatment and how this affected HIV treatment outcomes. METHODS: We reviewed clinical records of HIV patients aged 13 years and above, treated with rifampicin-based TB treatment while on PIs between1st-January -2013 and 30th-September-2018 from twelve public HIV clinics in Uganda. Appropriate PI prescription during rifampicin-based TB treatment was defined as; prescribing doubled dose lopinavir/ritonavir- (LPV/r 800/200 mg twice daily) and inappropriate PI prescription as prescribing standard dose LPV/r or atazanavir/ritonavir (ATV/r). RESULTS: Of the 602 patients who were on both PIs and rifampicin, 103 patients (17.1% (95% CI: 14.3-20.34)) received an appropriate PI prescription. There were no significant differences in the two-year mortality (4.8 vs. 5.7%, P = 0.318), loss to follow up (23.8 vs. 18.9%, P = 0.318) and one-year post TB treatment virologic failure rates (31.6 vs. 30.7%, P = 0.471) between patients that had an appropriate PI prescription and those that did not. However, more patients on double dose LPV/r had missed anti-retroviral therapy (ART) days (35.9 vs 21%, P = 0.001). CONCLUSION: We conclude that despite availability of clinical evidence, double dosing LPV/r in patients receiving rifampicin-based TB treatment is low in Uganda's public HIV clinics but this does not seem to affect patient survival and viral suppression.

Safety and efficacy of hydroxychloroquine for treatment of non-severe COVID-19 among adults in Uganda: a randomized open label phase II clinical trial.

BACKGROUND: Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. DESIGN: We conducted a randomized open label Phase II clinical trial from October-December 2020. METHODS: Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. RESULTS: Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3-4) vs 4(2-4): p = 0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. CONCLUSION: Our results show that HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution among adults with COVID-19 in Uganda. TRIAL REGISTRATION:  NCT04860284.

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

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

The rural Uganda non-communicable disease (RUNCD) study: prevalence and risk factors of self-reported NCDs from a cross sectional survey.

BACKGROUND: Non-communicable diseases (NCDs) are an increasing global concern, with morbidity and mortality largely occurring in low- and middle-income settings. We established the prospective Rural Uganda Non-Communicable Disease (RUNCD) cohort to longitudinally characterize the NCD prevalence, progression, and complications in rural Africa. METHODS: We conducted a population-based census for NCD research. We systematically enrolled adults in each household among three sub-counties of the larger Nakaseke Health district and collected baseline demographic, health status, and self-reported chronic disease information. We present our data on self-reported chronic disease, as stratified by age, sex, educational attainment, and sub-county. RESULTS: A total of 16,694 adults were surveyed with 10,563 (63%) respondents enrolled in the self-reported study. Average age was 37.8 years (SD = 16.5) and 45% (7481) were male. Among self-reported diseases, hypertension (HTN) was most prevalent (6.3%). 1.1% of participants reported a diagnosis of diabetes, 1.1% asthma, 0.7% COPD, and 0.4% kidney disease. 2.4% of the population described more than one NCD. Self-reported HTN was significantly higher in the peri-urban subcounty than in the other two rural sub-counties (p < 0.001); diagnoses for all other diseases did not differ significantly between sub-counties. Odds for self-reported HTN increased significantly with age (OR = 1.87 per 10 years of age, 95% CI 1.78-1.96). Male sex was associated with lower odds of reporting asthma (OR = 0.53, 95% CI 0.34-0.82) or HTN (OR = 0.31, 95% CI 0.26-0.40). CONCLUSIONS: The RUNCD will establish one of the largest NCD patient cohorts in rural Africa. First analysis highlights the feasibility of systematically enrolling large numbers of adults living in a rural Ugandan district. In addition, our study demonstrates low levels of self-reported NCDs compared to the nation-wide established levels, emphasizing the need to better educate, characterize, and care for the majority of rural communities.

Health Workers' Practices in Assessment and Management of Children with Respiratory Symptoms in Primary Care Facilities in Uganda: A FRESH AIR Descriptive Study.

INTRODUCTION: Globally, acute lower respiratory infections are the leading cause of mortality among children under 5 years. Following World Health Organization primary care guidelines, pneumonia is diagnosed based on cough/difficult breathing and fast breathing. We aimed to describe the practices of healthcare workers in primary care health facilities in Uganda in the management of young children with respiratory symptoms especially regarding asthma as opposed to pneumonia. METHODS: Health workers were observed during clinical consultations with children 1-59 months of age presenting with cough and/or difficult breathing at recruitment. Afterward, an exit interview with the caregiver was conducted. Health center availability of clinical guidelines, equipment and supplies for management of children with respiratory symptoms was assessed systematically. RESULTS: A total of 218 consultations with 50 health workers at six health centers were included. Median consultation time was 4 min. Health workers asked history relevant to distinguishing asthma from pneumonia in 16% of consultations. The respiratory rate was counted in 10%. Antibiotics were prescribed to 32% of all the children and to 39% of children diagnosed with pneumonia. Caregivers reported being informed of findings and possible diagnosis in 5% of cases. Medicine and equipment needed for diagnosing and treating asthma were generally unavailable. CONCLUSION: Clinical practices among Ugandan health workers in primary care are insufficient to distinguish between main causes of respiratory symptoms, especially asthma as opposed to pneumonia, in children under five. Irrational use of antibiotics is widespread. Clear communication with caregivers is lacking. This could be due to lack of relevant competencies, medicines, time and supplies. LAY SUMMARY: Globally, the most frequent cause of death for children under five is infections in the lower airways. The World Health Organization recommends that in local health clinics this is defined as cough/difficult breathing and fast breathing. This article focuses on the practices of local health workers in Uganda and how they in practice diagnose and treat children under five with these symptoms. In addition, we try to estimate how much the caregivers of the children understand from the consultation. This is done by observing the healthcare workers (HCWs) and by interviewing the caregivers. In general, we found that the consultations were too short, that too few of the health workers looked for important signs for lower airways disease such as fast breathing and that antibiotics were prescribed in too many of the consultations. Also, the length and quality of the consultations and the supplies at the local health clinics were not sufficient to diagnose and treat asthma, which can often be mistaken for an infection. We believe that it is an important problem that too few children with asthma are being diagnosed correctly and that antibiotics are being prescribed too frequently, the latter being an important cause of antibiotic resistance. Relevant action must be taken to improve this.

Implementing lung health interventions in low- and middle-income countries: a FRESH AIR systematic review and meta-synthesis.

The vast majority of patients with chronic respiratory disease live in low- and middle-income countries (LMICs). Paradoxically, relevant interventions often fail to be effective particularly in these settings, as LMICs lack solid evidence on how to implement interventions successfully. Therefore, we aimed to identify factors critical to the implementation of lung health interventions in LMICs, and weigh their level of evidence.This systematic review followed Cochrane methodology and Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting standards. We searched eight databases without date or language restrictions in July 2019, and included all relevant original, peer-reviewed articles. Two researchers independently selected articles, critically appraised them (using Critical Appraisal Skills Programme (CASP)/Meta Quality Appraisal Tool (MetaQAT)), extracted data, coded factors (following the Consolidated Framework for Implementation Research (CFIR)), and assigned levels of confidence in the factors (via Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual)). We meta-synthesised levels of evidence of the factors based on their frequency and the assigned level of confidence (PROSPERO:CRD42018088687).We included 37 articles out of 9111 screened. Studies were performed across the globe in a broad range of settings. Factors identified with a high level of evidence were: 1) "Understanding needs of local users"; 2) ensuring "Compatibility" of interventions with local contexts (cultures, infrastructures); 3) identifying influential stakeholders and applying "Engagement" strategies; 4) ensuring adequate "Access to knowledge and information"; and 5) addressing "Resource availability". All implementation factors and their level of evidence were synthesised in an implementation tool.To conclude, this study identified implementation factors for lung health interventions in LMICs, weighed their level of evidence, and integrated the results into an implementation tool for practice. Policymakers, non-governmental organisations, practitioners, and researchers may use this FRESH AIR (Free Respiratory Evaluation and Smoke-exposure reduction by primary Health cAre Integrated gRoups) Implementation tool to develop evidence-based implementation strategies for related interventions. This could increase interventions' implementation success, thereby optimising the use of already-scarce resources and improving health outcomes.

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

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