Chronic pulmonary aspergillosis (CPA) is a spectrum of several progressive disease manifestations caused by Aspergillus species in patients with underlying structural lung diseases. Duration of symptoms longer than three months distinguishes CPA from acute and subacute invasive pulmonary aspergillosis. CPA affects over 3 million individuals worldwide. Its diagnostic approach requires a thorough Clinical, Radiological, Immunological and Mycological (CRIM) assessment. The diagnosis of CPA requires (1) demonstration of one or more cavities with or without a fungal ball present or nodules on chest imaging, (2) direct evidence of Aspergillus infection or an immunological response to Aspergillus species and (3) exclusion of alternative diagnoses, although CPA and mycobacterial disease can be synchronous. Aspergillus antibody is elevated in over 90% of patients and is the cornerstone for CPA diagnosis. Long-term oral antifungal therapy improves quality of life, arrests haemoptysis and prevents disease progression. Itraconazole and voriconazole are alternative first-line agents; voriconazole is preferred for patients with contra-indications to itraconazole and in those with severe disease (including large aspergilloma). In patients co-infected with tuberculosis (TB), it is not possible to treat TB with rifampicin and concurrently administer azoles, because of profound drug interactions. In those with pan-azole resistance or intolerance or progressive disease while on oral triazoles, short-term courses of intravenous liposomal amphotericin B or micafungin is used. Surgery benefits patients with well-circumscribed simple aspergillomas and should be offered earlier in low-resource settings.

Invasive fungal diseases (IFDs) are of huge concern in resource-limited settings, particularly in Africa, due to the unavailability of diagnostic armamentarium for IFDs, thus making definitive diagnosis challenging. IFDs have non-specific systemic manifestations overlapping with more frequent illnesses, such as tuberculosis, HIV, and HIV-related opportunistic infections and malignancies. Consequently, IFDs are often undiagnosed or misdiagnosed. We critically reviewed the available literature on IFDs in Africa to provide a better understanding of their epidemiology, disease burden to guide future research and interventions. Cryptococcosis is the most encountered IFD in Africa, accounting for most of the HIV-related deaths in sub-Saharan Africa. Invasive aspergillosis, though somewhat underdiagnosed and/or misdiagnosed as tuberculosis, is increasingly being reported with a similar predilection towards people living with HIV. More cases of histoplasmosis are also being reported with recent epidemiological studies, particularly from Western Africa, showing high prevalence rates amongst presumptive tuberculosis patients and patients living with HIV. The burden of pneumocystis pneumonia has reduced significantly probably due to increased uptake of anti-retroviral therapy among people living with HIV both in Africa, and globally. Mucormycosis, talaromycosis, emergomycosis, blastomycosis, and coccidiomycosis have also been reported but with very few studies from the literature. The emergence of resistance to most of the available antifungal drugs in Africa is yet of huge concern as reported in other regions. IFDs in Africa is much more common than it appears and contributes significantly to morbidity and mortality. Huge investment is needed to drive awareness and fungi related research especially in diagnostics and antifungal therapy.

Comorbid conditions and adverse drug events are associated with poor treatment outcomes among patients with drug resistant tuberculosis (DR – TB). This study aimed at determining the treatment outcomes of DR – TB patients with poor prognostic indicators in Uganda. We reviewed treatment records of DR – TB patients from 16 treatment sites in Uganda. Eligible patients had confirmed DR – TB, a treatment outcome in 2014–2019 and at least one of 15 pre-defined poor prognostic indicators at treatment initiation or during therapy. The pre-defined poor prognostic indicators were HIV co-infection, diabetes, heart failure, malignancy, psychiatric illness/symptoms, severe anaemia, alcohol use, cigarette smoking, low body mass index, elevated creatinine, hepatic dysfunction, hearing loss, resistance to fluoroquinolones and/or second-line aminoglycosides, previous exposure to second-line drugs (SLDs), and pregnancy. Tuberculosis treatment outcomes were treatment success, mortality, loss to follow up, and treatment failure as defined by the World Health Organisation. We used logistic and cox proportional hazards regression analysis to determine predictors of treatment success and mortality, respectively. Of 1122 DR – TB patients, 709 (63.2%) were male and the median (interquartile range, IQR) age was 36.0 (28.0–45.0) years. A total of 925 (82.4%) had ≥2 poor prognostic indicators. Treatment success and mortality occurred among 806 (71.8%) and 207 (18.4%) patients whereas treatment loss-to-follow-up and failure were observed among 96 (8.6%) and 13 (1.2%) patients, respectively. Mild (OR: 0.57, 95% CI 0.39–0.84, p = 0.004), moderate (OR: 0.18, 95% CI 0.12–0.26, p < 0.001) and severe anaemia (OR: 0.09, 95% CI 0.05–0.17, p < 0.001) and previous exposure to SLDs (OR: 0.19, 95% CI 0.08–0.48, p < 0.001) predicted lower odds of treatment success while the number of poor prognostic indicators (HR: 1.62, 95% CI 1.30–2.01, p < 0.001), for every additional poor prognostic indicator) predicted mortality. Among DR – TB patients with multiple poor prognostic indicators, mortality was the most frequent unsuccessful outcomes. Every additional poor prognostic indicator increased the risk of mortality while anaemia and previous exposure to SLDs were associated with lower odds of treatment success. The management of anaemia among DR – TB patients needs to be evaluated by prospective studies. DR – TB programs should also optimise DR – TB treatment the first time it is initiated.

Background: Gender differences among patients with drug resistant tuberculosis (DRTB) and HIV co-infection could affect treatment outcomes. We compared characteristics and treatment outcomes of DRTB/HIV co-infected men and women in Uganda. Methods: We conducted a retrospective chart review of patients with DRTB from 16 treatment sites in Uganda. Eligible patients were aged ≥ 18 years, had confirmed DRTB, HIV co-infection and a treatment outcome registered between 2013 and 2019. We compared socio-demographic and clinical characteristics and tuberculosis treatment outcomes between men and women. Potential predictors of mortality were determined by cox proportional hazard regression analysis that controlled for gender. Statistical significance was set at p < 0.05. Results: Of 666 DRTB/HIV co-infected patients, 401 (60.2%) were men. The median (IQR) age of men and women was 37.0 (13.0) and 34.0 (13.0) years respectively (p < 0.001). Men were significantly more likely to be on tenofovir-based antiretroviral therapy (ART), high-dose isoniazid-containing DRTB regimen and to have history of cigarette or alcohol use. They were also more likely to have multi-drug resistant TB, isoniazid and streptomycin resistance and had higher creatinine, aspartate and gamma-glutamyl aminotransferase and total bilirubin levels. Conversely, women were more likely to be unemployed, unmarried, receive treatment from the national referral hospital and to have anemia, a capreomycin-containing DRTB regimen and zidovudine-based ART. Treatment success was observed among 437 (65.6%) and did not differ between the genders. However, mortality was higher among men than women (25.7% vs. 18.5%, p = 0.030) and men had a shorter mean (standard error) survival time (16.8 (0.42) vs. 19.0 (0.46) months), Log Rank test (p = 0.046). Predictors of mortality, after adjusting for gender, were cigarette smoking (aHR = 4.87, 95% CI 1.28–18.58, p = 0.020), an increase in alanine aminotransferase levels (aHR = 1.05, 95% CI 1.02–1.07, p < 0.001), and history of ART default (aHR = 3.86, 95% CI 1.31–11.37, p = 0.014) while a higher baseline CD4 count was associated with lower mortality (aHR = 0.94, 95% CI 0.89–0.99, p = 0.013 for every 10 cells/mm³ increment). Conclusion: Mortality was higher among men than women with DRTB/HIV co-infection which could be explained by several sociodemographic and clinical differences.

Background: Undernutrition is associated with unfavourable treatment outcomes among people with drug-resistant tuberculosis (DRTB). Factors influencing the treatment outcomes among undernourished people with DRTB are not well characterised. The aim of this study was to determine factors associated with treatment success among undernourished people with DRTB in Uganda. Methods: We analysed data from a retrospective cohort of people with DRTB from 16 treatment sites in Uganda. We included participants with a pre-treatment body mass index (BMI) of < 18.5 kilograms/meters² (kg/m²). Participants were categorised as having mild (BMI of 18.5– 17 kg/m²), moderate (BMI of 16.9– 16.0 kg/m²) or severe (BMI of < 16.0 kg/m²) undernutrition. We performed logistic regression analysis to determine factors associated with treatment success. Results: Among 473 people with DRTB, 276 (58.4%) were undernourished (BMI < 18.5 Kg/m²) and were included in the study. Of these, 92 (33.3%) had mild, 69 (25.0%) had moderate and 115 (41.7%) had severe undernutrition. The overall treatment success rate (TSR) for the undernourished was 71.4% (n = 197). Although the TSR was similar among participants with mild (71.7%), moderate (78.3%) and severe (67.0%) undernutrition (p = 0.258), all treatment failure cases (n =6) were among participants with severe undernutrition (p = 0.010). Cigarette smoking (odds ratio (OR) = 0.19, 95% CI 0.07– 0.47, p < 0.001), urban residence (OR = 0.31, 95% CI 0.14– 0.70, p = 0.005) and moderate (OR = 0.14, 95% CI 0.06– 0.35, p < 0.001) and severe anaemia (OR = 0.06, 95% CI 0.01– 0.29, p = 0.001) were associated with lower odds of treatment success. Conclusion: Most undernourished people with DRTB have severe undernutrition. Smoking and anaemia are modifiable factors which upon appropriate intervention could improve treatment success. The effect of urban residence on the TSR needs to be evaluated further.

Background: Pulmonary multi-drug-resistant tuberculosis (MDR TB) alters lung architecture and involves lengthy treatment duration, high pill burden, drug adverse effects, travel restrictions, and stigma. Literature about pulmonary function and health-related quality of life (QoL) of patients treated for MDR TB is limited. This study sought to determine the prevalence of chronic obstructive pulmonary disease (COPD) and QoL of patients who were treated for pulmonary MDR TB. Methods: Participants who completed 18 months of pulmonary MDR TB treatment and considered cured were eligible to be evaluated in a cross-sectional study. We performed post-bronchodilator spirometry to measure forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC). COPD was defined as FEV₁/FVC < 0.7; health-related QoL was assessed using the Medical Outcomes Survey for HIV (MOS-HIV) and St. George’s Respiratory Questionnaire (SGRQ). Linear and logistic regression models were used to assess associations with COPD, health-related QoL, and other characteristics of the cohort. Results: A total of 95 participants were enrolled. Median age of the cohort was 39 years (interquartile range (IQR), 29–45), and 55 (58%) were HIV-positive. COPD prevalence was 23% (22/95). Median SGRQ score was normal at 7.8 (IQR, 3.1–14.8). Median mental and physical health summary scores were significantly impaired, at 58.6 (IQR, 52.0–61.5) and 52.9 (IQR, 47.8–57.9), respectively, on a scale of 0 to 100 where 100 represents excellent physical or mental health. In this sample, 19% (18/95) of participants were in the lowest relative socioeconomic position (SEP) while 34% (32/95) were in the highest relative SEP. Belonging in the lowest SEP group was the strongest predictor of COPD. Conclusion: Individuals who have completed MDR TB treatment have a high prevalence of COPD and low mental and physical health summary scores. Our study highlights the need for pulmonary rehabilitation programs in patients with a low socioeconomic position (SEP) after MDR TB treatment.