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.

Prevalence of chronic pulmonary aspergillosis along the continuum of pulmonary tuberculosis care: A protocol for a living systematic review and meta-analysis.

INTRODUCTION: Chronic pulmonary aspergillosis (CPA) is a debilitating disease estimated to affect over 3 million people worldwide. Pulmonary tuberculosis (PTB) is the most significant risk factor for CPA. However, the true burden of CPA at the time of PTB diagnosis, during, and after PTB treatment remains unknown. In this paper, we present a protocol for a living systematic review aimed at estimating the current burden of CPA along the continuum of PTB care. MATERIALS AND METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines to formulate this protocol, which is registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023453900). We will identify primary literature through various electronic databases, including CINAHL, Ovid MEDLINE, MEDLINE (PubMed), EMBASE, Google Scholar, Cochrane Database of Systematic Reviews, and African Journal Online. The search will encompass articles from inception to December 31st, 2023, using medical subject heading search terms "pulmonary tuberculosis" AND "chronic pulmonary aspergillosis". Two reviewers will independently assess titles, abstracts, and full texts for eligibility using the Covidence web-based software. The eligible studies will comprise original observational research that reports on the prevalence of CPA diagnosed in individuals with PTB, based on established criteria, without language or geographic restriction. We intend to exclude single case reports and case series with fewer than 10 participants, as well as review articles, guidelines, and letters to the editors. Cochrane Risk of Bias Tools (ROB2 and ROBINS-I) will used to assess study quality and risk of bias and the quality of the evidence will be rated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. Our data syntheses will encompass meta-analysis and meta-regression, conducted using STATA version 18 and R- Studio version 4.0.2. This systematic review will be updated every 3-5 years as more data emerges. CONCLUSIONS: The findings of this proposed systematic review will summarize the available evidence on the occurrence of CPA, at the time of PTB diagnosis, during and after PTB treatment. The study results have the potential to guide healthcare policies regarding screening for CPA, enhance clinical decision-making, and catalyse further research into understanding the interplay between PTB and CPA. By shedding light on the current burden of CPA along the continuum of PTB care, we aspire to contribute to the betterment of patient care, disease management, and global health outcomes. PROSPERO REGISTRATION: CRD42023453900.

The Impact of Chronic Pulmonary Aspergillosis Co-infection on the Health-Related Quality of Life of Patients with Pulmonary Tuberculosis in Uganda.

BACKGROUND: Both pulmonary tuberculosis (PTB) and chronic pulmonary aspergillosis (CPA) significantly affect health-related quality of life (HR-QoL). We aimed to determine the impact of CPA co-infection on the HR-QoL of Ugandans with PTB. METHODS: We conducted a prospective study as part of a larger study among participants with PTB with persistent pulmonary symptoms after 2 months of anti-TB treatment at Mulago Hospital, Kampala, Uganda between July 2020 and June 2021. HR-QoL was assessed using St. George Respiratory Questionnaire (SGRQ) at enrollment and at the end of PTB treatment (4 months apart). SGRQ scores range from 0 to 100, with higher score representing a poorer HR-QoL. RESULTS: Of the 162 participants enrolled in the larger study, 32 (19.8%) had PTB + CPA and 130 (80.2%) had PTB. The baseline characteristics of the two groups were comparable. Regarding overall health, a higher proportion of the PTB group rated their HR-QoL as "very good" compared to those who had PTB + CPA (68 [54.0%] versus 8 [25.8%]). At enrollment, both groups had comparable median SGRQ scores. However, at follow up, the PTB group had statistically significantly better SGRQ scores (interquartile range); symptoms (0 [0-12.4] versus 14.4 [0-42.9], p < 0.001), activity ((0 [0-17.1] versus 12.2 [0-35.5], p = .03), impact (0 [0-4.0] versus 3.1 [0-22.5], p = 0.004), and total scores ((0 [0-8.5] versus 7.6[(0-27.4], p = 0.005). CONCLUSION: CPA co-infection impairs HR-QoL of people with PTB. Active screening and management of CPA in patients with PTB is recommended to improve HR-QoL of these individuals.

Prevalence of and Factors Associated with Hypertension Among Adults on Dolutegravir-Based Antiretroviral Therapy in Uganda: A Cross Sectional Study.

Introduction: Dolutegravir-based anti-retroviral therapy (ART) regimens were rolled out as first line HIV treatment in Uganda due to their tolerability, efficacy and high resistance barrier to human immunodeficiency virus (HIV). They have however been associated with weight gain, dyslipidemia and hyperglycemia which are cardiometabolic risk factors of hypertension. We assessed the prevalence and factors associated with hypertension among adults on dolutegravir regimens. Methods: We conducted a cross-sectional study on 430 systematically sampled adults on dolutegravir-based ART for ≥ 6 months. Hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or history of use of antihypertensive agents. Results: The prevalence of hypertension was 27.2% (117 of 430 participants) [95% CI: 23.2-31.6]. Majority were female (70.7%), the median age 42 [34, 50] years, with body mass index (BMI) ≥ 25 kg/m3 (59.6%) and median duration on DTG-based regimens of 28 [15, 33] months. Being male [aPR: 1.496, 95% CI: 1.122-1.994, P = 0.006], age ≥ 45 years [aPR: 4.23, 95% CI: 2.206-8.108, P < 0.001] and 35-44 years [aPR: 2.455, 95% CI: 1.216-4.947, P < 0.012] as compared with age < 35 years, BMI ≥ 25 kg/m3 [aPR: 1.489, 95% CI: 1.072-2.067, P = 0.017] as compared with BMI < 25 kg/m3, duration on dolutegravir-based ART [aPR: 1.008, 95% CI: 1.001-1.015, P = 0.037], family history of hypertension [aPR: 1.457, 95% CI: 1.064-1.995, P = 0.019] and history of heart disease [aPR: 1.73, 95% CI: 1.205-2.484, P = 0.003] were associated with hypertension. Conclusion: One in every four people with HIV (PWH) on dolutegravir-based ART has hypertension. We recommend the integration of hypertension management in the HIV treatment package and policies to improve existing supply chains for low cost and high-quality hypertension medications.

The Impact of Chronic Pulmonary Aspergillosis Co-infection on the Health-Related Quality of Life of Patients with Pulmonary Tuberculosis in Uganda.

Background Both pulmonary tuberculosis (PTB) and chronic pulmonary aspergillosis (CPA) significantly affect health-related quality of life (HR-QoL). We aimed to determine the impact of CPA co-infection on the HR-QoL of Ugandans with PTB. Methods We conducted a prospective study among participants with PTB with persistent pulmonary symptoms after 2 months of anti-TB treatment at Mulago Hospital, Kampala, Uganda between July 2020 and June 2021. HR-QoL was assessed using St. George Respiratory Questionnaire (SGRQ) at enrollment and at the end of PTB treatment (4 months apart). SGRQ scores range from 0 to 100, with higher score representing a poorer HR-QoL. Results Of the 162 participants enrolled, 32 (19.8%) had CPA + PTB and 130 (80.2%) had PTB only. The baseline characteristics of the two groups were comparable. Regarding overall health, a higher proportion of the PTB only group rated their HR-QoL as "very good" compared to those who had both TB and CPA (68 (54.0%) versus 8 (25.8%)). At enrollment, both groups had comparable median SGRQ scores. However, at follow up, the PTB only group had statistically significantly better SGRQ scores (interquartile range); symptoms (0 (0 - 12.4) versus 14.4 (0 - 42.9), p < 0.001), activity ((0 (0 - 17.1) versus 12.2 (0 - 35.5), p = .03), impact (0 (0 - 4.0) versus 3.1 (0 - 22.5), p = 0.004), and total scores ((0 (0 - 8.5) versus 7.6 (0 - 27.4), p = 0.005). Conclusion CPA co-infection impairs HR-QoL of people with PTB. Active screening and management of CPA in patients with PTB is recommended to improve HR-QoL of these individuals.

Chronic pulmonary aspergillosis in patients with active pulmonary tuberculosis with persisting symptoms in Uganda.

BACKGROUND: The occurrence of chronic pulmonary aspergillosis (CPA) among drug sensitive pulmonary tuberculosis (PTB) patients on optimal therapy with persistent symptoms was investigated. METHODS: We consecutively enrolled participants with PTB with persistent pulmonary symptoms after 2 months of anti-TB treatment at Mulago Hospital, Kampala, Uganda, between July 2020 and June 2021. CPA was defined as a positive Aspergillus-specific IgG/IgM immunochromatographic test (ICT), a cavity with or without a fungal ball on chest X-ray (CXR), and compatible symptoms >3 months. RESULTS: We enrolled 162 participants (median age 30 years; IQR: 25-40), 97 (59.9%) were male, 48 (29.6%) were HIV-infected and 15 (9.3%) had prior PTB. Thirty-eight (23.4%) sputum samples grew A. niger and 13 (8.0%) A. fumigatus species complexes. Six (3.7%) participants had intracavitary fungal balls and 52 (32.1%) had cavities. Overall, 32 (19.8%) participants had CPA. CPA was associated with prior PTB (adjusted odds ratio [aOR]: 6.61, 95% CI: 1.85-23.9, p = .004), and far advanced CXR changes (aOR: 4.26, 95% CI: 1.72-10.52, p = .002). The Aspergillus IgG/IgM ICT was positive in 10 (31.3%) participants with CPA. CONCLUSIONS: Chronic pulmonary aspergillosis may cause persistent respiratory symptoms in up to one-fifth of patients after intensive treatment for PTB. The Aspergillus IgG/IgM ICT positivity rate was very low and may not be used alone for the diagnosis of CPA in Uganda.

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.

Prevalence and factors associated with non-adherence to multi-drug resistant tuberculosis (MDR-TB) treatment at Mulago National Referral Hospital, Kampala, Uganda.

BACKGROUND: In Uganda, 12% of previously treated TB cases and 1.6% of new cases have MDR-TB and require specialized treatment and care. Adherence is crucial for improving MDR-TB treatment outcomes. There is paucity of information on the extent to which these patients adhere to treatment and what the drivers of non-adherence are. METHODS: We conducted a cohort study using retrospectively collected routine program data for patients treated for MDR-TB between January 2012 - May 2016 at Mulago Hospital. We extracted anonymized data on non-adherence (missing 10% or more of DOT), socio-economic, demographic, and treatment characteristics of the patients. All participants were sensitive to MDR-TB drugs after second line Drug Susceptible Testing (DST) at entry into the study. Factors associated with non-adherence to MDR-TB treatment were determined using generalized linear models for the binomial family with log link and robust standard errors. We considered a p- value less than 0.05 as statistically significant. RESULTS: The records of 227 MDR- TB patients met the inclusion criteria, 39.4% of whom were female, 32.6% aged between 25 - 34 years, and 54.6% living with HIV/AIDS. About 11.9% of the patients were non-adherent. The main driver for non-adherence was history of previous DR-TB treatment; previously treated DR-TB patients were 3.46 (Adjusted prevalence ratio: 3.46, 95 % CI: 1.68 - 7.14) times more likely to be non-adherent. CONCLUSION: One in 10 MDR-TB patients treated at Mulago hospital is non-adherent to treatment. History of previous DRTB treatment was significantly associated with non-adherence in this study. MDR-TB program should strengthen adherence counselling, strengthen DST surveillance, and close monitoring for previously treated DR-TB patients.

Estimation of the burden of tinea capitis among children in Africa.

Tinea capitis is a common and endemic dermatophytosis among school age children in Africa. However, the true burden of the disease is unknown in Africa. We aimed to estimate the burden of tinea capitis among children <18 years of age in Africa. A systematic review was performed using Embase, MEDLINE and the Cochrane Library of Systematic Reviews to identify articles on tinea capitis among children in Africa published between January 1990 and October 2020. The United Nation's Population data (2019) were used to identify the number of children at risk of tinea capitis in each African country. Using the pooled prevalence, the country-specific and total burden of tinea capitis was calculated. Forty studies involving a total of 229,086 children from 17/54 African countries were identified and included in the analysis. The pooled prevalence of tinea capitis was 23% (95% CI, 17%-29%) mostly caused by Trichophyton species. With a population of 600 million (46%) children, the total number of cases of tinea capitis in Africa was estimated at 138.1 (95% CI, 102.0-174.1) million cases. Over 96% (132.6 million) cases occur in sub-Saharan Africa alone. Nigeria and Ethiopia with the highest population of children contributed 16.4% (n = 98.7 million) and 8.5% (n = 52.2 million) of cases, respectively. Majority of the participants were primary school children with a mean age of 10 years. Cases are mostly diagnosed clinically. There was a large discrepancy between the clinical and mycological diagnosis. About one in every five children in Africa has tinea capitis making it one of the most common childhood conditions in the region. A precise quantification of the burden of this neglected tropical disease is required to inform clinical and public health intervention strategies.