Current Organisation

Mbarara University of science and technology

Current Job Title

Research Fellow

Biography

Publications

Project Title

Metabolic and molecular ecological evolution of opportunistic pulmonary fungal co-infections (MeMoF)

EDCTP Project Call

Career Development Fellowship (CDF)

Host Organisation

Project Objectives

Objectives 1. To determine the burden and etiological profiles of fungal-co-infections among patients with chronic pulmonary disease 2. To establish and characterise microbial communities associated with chronic pulmonary disease. 3. To characterise potential interaction relationships established between fungal and bacterial communities.

Study Design

Cross-sectional study

Project Summary

The action point of this project was to investigate the Metabolic and Molecular Ecological Evolution of Opportunistic Pulmonary Fungal Co-Infections (MeMoF). Through serial observations, we have noted that many of the so called TB suspected patients presented with long standing chronic pulmonary symptoms that persisted even after being initiated on anti-TB treatment. However, for some reasons, these incidences have been attributed to anti-TB drug resistance clinically. Yet, in as much as this could be true, we had earlier tried to investigate the possibility off target aetiology that could perhaps enhance the clinical presentations seen in this patient cohort. Indeed, we were able to determine the prevalence of pulmonary fungal coinfections to be over 70% in about 130 patients. So through the MeMoF project we hypothesized that (1) The burden of opportunistic pulmonary fungal co-infections is higher than culture dependent data might suggest (2) Culture independent data complements culture dependent data in supporting therapeutic decisions (3) Fungal-bacterial co-existence influences fungal virulence; and Thus, through the MeMoF project, we aimed 1) To determine the burden and etiological profiles of fungal-co-infections among patients with chronic pulmonary disease. 2) To establish and characterize microbial communities associated with chronic pulmonary disease and 3) To characterize potential interaction relationships established between fungal and bacterial communities. Thus, to answer these questions, we designed a laboratory-based observational cross-sectional study. Based on the preliminary data we determined a sample size of 369 patients with the following characteristics. Accordingly; our target population were patients that reported at the HIV/TB clinic of Mbarara Regional referral hospital in line with the existing diagnosis and point of care procedures. The target cohort were patients suspected of TB and were included if they were 18 years and older, provided consent with at least one of the following qualities; Presenting with Pulmonary Tuberculosis (PTB)-like symptoms, having no prior history of TB, testing positive or negative on smear test and GeneXpert test, exhibiting Lipoarabinomannan antigen positivity along with persistent respiratory symptoms and being on anti-TB treatment and severely ill yet able to produce sputum. From these patients’ baseline data was collected using a questionnaire, additionally, two (an on-spot and early morning) sputum samples were collected to establish TB, fungal, non-TB bacterial aetiology; and antimicrobial susceptibility patterns using conventional basic and advanced bacterial and fungal analytical techniques including culture, GeneXpert, and targeted PCR methods. We managed to collect data from 334 participants which we assumed to be representative enough. Out of these, we have so far analysed 151 complete data sets, while we wait for the completion of the other data sets. Through this analysis we have determined general cause of infection by either TB (0.7%), Fungi (1.3%) and or non-TB Bacteria (4.6%). Cross microbial poly aetiological prevalence’s included TB and non-TB bacteria at 4.0%, TB and Fungal at 5.3% Fungal and non-TB aetiology was at 55.6%. Yet Tri-cross-kingdom aetiology between TB, Fungal and Non-TB aetiology was at 28.5% As far as aetiology is concerned; the common microbial communities identified were diverse enough and included, Mycobacterium tuberculosis (MTB), filamentous fungi including Acremonium spp, Aspergillus spp, Penicillium spp and Bipolaris spp; Yeasts such as Candida albicans, and Non albicans Candida (NAC) species including C. famata, C. guillermondi; Dimorphic fungi including Cryptococcus neoformans and Histoplasma capsulatum; and common non-TB bacteria, such as Klebsiella pneumoniae, Streptococcus pneumoniae, E.coli, Proteus spp and Staphylococcus aureus. As shown in Figure 1 above, we see a possibility of fungal-bacterial cross-kingdom aetiology, the question thus becomes, what is the impact of fungal-bacterial cross kingdom aetiology on patient outcomes. While we recognize tuberculosis and HIV as a major and longstanding co-infection scenario, it’s prudent that other possible co-infections are also investigated and brought to light. These cross-kingdom interactions can possibly complicate our superficial view of disease outcomes and may require a much deeper insight into the molecular and metabolic aspects. Indeed, fungi and bacteria are known to formulate all sorts ofrelationships ranging from mutualistic, commensalitic, antagonistic and endosymbiotic modes. All these can impact disease progression differently when established in a common infection niche. Whether this is what happens in this patient cohort, it remains to be investigated further. All in all, EDCTP through the MeMoF project has projected a twist in microbial aetiology and though further investigations are required we are confident that the information here forth will help shape clinical management of such patients going forward.

Results & Outcomes