Chronic pulmonary aspergillosis is common among patients with presumed tuberculosis relapse in Ghana.

Chronic pulmonary aspergillosis (CPA) may mimic pulmonary tuberculosis (PTB). The two diseases are clinically indistinguishable and may result in CPA misdiagnosed as PTB or vice versa. Although PTB is largely recognised as a differential diagnosis of CPA and often ruled out prior to CPA diagnosis, the reverse is uncommon. The aim of this study was to determine the proportion of CPA cases among patients being assessed for PTB. A cross-sectional survey was conducted among consecutive patients referred for GeneXpert Mycobacterium tuberculosis test for the diagnosis of PTB at the Korle-Bu Teaching Hospital, Accra, Ghana. Patients' demographics, clinical and socioeconomic details were obtained using a structured questionnaire. Blood was collected for Aspergillus and HIV serology, and sputum samples obtained for Aspergillus culture. Chest radiograph was obtained, and computed tomography scan was also done for patients with positive Aspergillus serology or cavitation. CPA was defined using an algorithm developed by the Global Action for Fungal Infections (GAFFI) international expert panel. A total of 154 patients were included in the analysis, of whom 134 (87%) did not have a prior PTB diagnosis. There were 41 (26.6%) GeneXpert positive cases. CPA prevalence was 9.7% overall, but 50% in patients with a prior history of PTB and 3.7% in those without previous PTB. Although CPA is rarely considered as a differential diagnosis of PTB in Ghana, our findings show that CPA may affect half of patients being assessed for PTB relapse. Efforts to diagnose CPA should be prioritised in this patient group.

Chronic pulmonary aspergillosis (CPA) may be misdiagnosed as pulmonary tuberculosis (PTB), or vice versa due to clinical similarities. Screening for CPA among patients undergoing investigation for relapsed PTB and new PTB revealed that half and about four in 100 patients, respectively, had CPA.

Tuberculosis patients with diabetes co-morbidity experience reduced Mycobacterium tuberculosis complex clearance.

Objective: This study aimed to investigate the impact of diabetes mellitus (DM) on tuberculosis (TB) treatment response using bacterial clearance as a surrogate marker. Method: We compared smear microscopy, culture, and tuberculosis molecular bacterial load assay (TB-MBLA) for treatment monitoring. Following that, bacterial clearance was longitudinally monitored among TB-only (TB without DM) and TB-diabetes (TBDM) patients using TB-MBLA. Results: Ninety-three participants, including 59 TB-only and 34 TBDM patients, were enrolled. TB-only patients exhibited higher upper zone infiltrations (32/35 vs 16/22, p = 0.059) suggesting a trend towards significance, and significantly more cavitation in the same zone (16/18 vs 7/13, p = 0.028). There was a high proportion of Mycobacterium africanum (Maf) among the TBDM cohort (p = 0.0044).At baseline, TB-only patients exhibited a higher average bacterial burden (4.49 logeCFU/mL) compared to the TBDM group (3.91 logeCFU/mL) (p = 0.042). The bacterial load in the TB-only group decreased significantly during treatment but the TBDM group experienced delayed clearance throughout the intensive phase of anti-TB treatment even at day 56 (p = 0.028). The TB-only group demonstrated a shorter median time to TB-MBLA conversion to negative (57 days) compared to the TBDM group (62 days) (p = 0.022). Conclusion: These findings underscore the urgent call for understanding the interplay between diabetes and TB, emphasizing the need for tailored interventions in optimizing TB care for individuals comorbid with diabetes.

Macrophage susceptibility to infection by Ghanaian Mycobacterium tuberculosis complex lineages 4 and 5 varies with self-reported ethnicity.

Background: The epidemiology of Mycobacterium tuberculosis complex (MTBC) lineage 5 (L5) infections in Ghana revealed a significantly increased prevalence in Ewes compared to other self-reported ethnic groups. In that context, we sought to investigate the early phase of tuberculosis (TB) infection using ex vivo infection of macrophages derived from the blood of Ewe and Akan ethnic group volunteers with MTBC L4 and L5 strains. Methods: The study participants consisted of 16 controls, among which self-reported Akan and Ewe ethnicity was equally represented, as well as 20 cured TB cases consisting of 11 Akans and 9 Ewes. Peripheral blood mononuclear cells were isolated from both healthy controls and cured TB cases. CD14+ monocytes were isolated and differentiated into monocyte-derived macrophages (MDMs) before infection with L4 or L5 endemic strains. The bacterial load was assessed after 2 hours (uptake) as well as 3 and 7 days post-infection. Results: We observed a higher capacity of MDMs from Ewes to phagocytose L4 strains (p < 0.001), translating into a higher bacillary load on day 7 (p < 0.001) compared to L5, despite the higher replication rate of L5 in Ewe MDMs (fold change: 1.4 vs. 1.2, p = 0.03) among the controls. On the contrary, within macrophages from Akans, we observed a significantly higher phagocytic uptake of L5 (p < 0.001) compared to L4, also translating into a higher load on day 7 (p = 0.04). However, the replication rate of L4 in Akan MDMs was higher than that of L5 (fold change: L4 = 1.2, L4 = 1.1, p = 0.04). Although there was no significant difference in the uptake of L4 and L5 among cured TB cases, there was a higher bacterial load of both L4 (p = 0.02) and L5 (p = 0.02) on day 7 in Ewe MDMs. Conclusion: Our results suggest that host ethnicity (driven by host genetic diversity), MTBC genetic diversity, and individual TB infection history are all acting together to modulate the outcome of macrophage infections by MTBC.

Mycologically confirmed chronic pulmonary aspergillosis in a post-pulmonary tuberculosis patient in Ghana.

Pulmonary tuberculosis (PTB) remains a major public health challenge in low- and middle-income countries. PTB may leave residual cavitation following treatment in some patients, allowing saprophytic colonization by Aspergillus species, resulting in a slow, progressive lung condition known as chronic pulmonary aspergillosis (CPA). PTB is the commonest underlying condition in CPA, mainly post-treatment. CPA is likely to be misdiagnosed as PTB reactivation due to clinical and radiological similarities. Ghana has a significant PTB burden, but only one case of clinically and radiologically diagnosed CPA has been reported, and epidemiological studies are also lacking. The definitive diagnosis of CPA comprises symptomatology, imaging findings and mycological evidence. Mycological evidence is critical to rule out other differential diagnoses, including non-Aspergillus pulmonary fungal infections and has implications for treatment choice. Herein, we present a case of mycologically-confirmed CPA in a previously treated PTB patient. Funding: Fungal laboratory testing was provided by a CARIGEST SA studentship and research award to BKO and DWD respectively.