Diagnosis and Epidemiology of Serious Fungal Infections in Ghana

Abstract

In many resource-limited settings, advances in diagnosis and epidemiology of serious fungal infections (SFIs), which generally excludes superficial fungal infections, are yet to be realized. However, there are significant number of patient groups at risk for SFIs, and the geography and socio-economic conditions are more favourable for SFIs in the general population. In these settings, SFIs are commonly diagnosed by histopathology, because antigen-antibody tests are less accessible. Recent introductions of fungal rapid diagnostics tests (RDTs) are revolutionizing SFI diagnosis globally. The aim of this research was to update the epidemiology of SFIs in Ghana, by using RDTs to aid the diagnosis of key SFIs among common at-risk patient groups and retrospectively evaluating histopathologically diagnosed SFIs. The research comprised five studies. Study 1: Patients living with HIV were screened for cryptococcosis and histoplasmosis using cryptococcal antigen (CrAg) lateral flow assay (LFA), Histoplasma antigen (Histo Ag) enzyme immunoassay (EIA) and LFA followed by confirmation with laboratory and medical imaging methods (n = 150); Study 2: Patients being investigated for new or relapsed pulmonary tuberculosis (PTB) were screened for chronic pulmonary aspergillosis (CPA) using Aspergillus-specific antibody LFA (Asp Ab LFA) in combination with medical imaging and culture (n = 183); Study 3: Patients with confirmed PTB, receiving anti-TB regimen were screened with Asp Ab LFA at the end of PTB treatment (T1) and six months post-treatment (T2) to detect CPA (n = 47); Study 4: Patients with haematological malignancy were screened for invasive aspergillosis (IA) using the Aspergillus galactomannan LFA, computed tomography scan and culture (n = 56); Study 5: Histopathology reports from 2012-2021 were reviewed to evaluate the spectrum of fungal infections (n = 107) and confirm aetiological agents with molecular methods. The prospective studies revealed the following: CrAg and Histo Ag prevalence rates were 2.7% (95% CI, 0.1 - 5.3%) and 4.7% (95% CI, 0.7 - 8.7%), respectively, with disease confirmed in all antigen-positive cases; CPA prevalence was 9.7% (95% CI, 5.0 -14.4%) overall, but was 50% (95% CI, 28 - 72%) in patients with previous PTB and 3.7% (95% CI, 0.5 - 6.9%) in those with no PTB history; the rate of new CPA development was 3.0% and 7.4% at T1 and T2, respectively with an overall incidence of 10.7% (90% CI, 1.1 - 20.3%) over 12 months; 5.4% (90% CI, 0.4 - 10.4%) of patients with haematological malignancy met the criteria for IA diagnosis. The retrospective study identified 107 cases of diverse fungal infections, including previously unreported infections. In conclusion, this thesis demonstrated that SFIs occur at significant rates among the major at-risk patient groups and diverse fungal infections are diagnosed in Ghana. Importantly, access to RDTs and histomolecular assays, improves case detection and diagnostic accuracy respectively. The key priority for further research is to undertake targeted large-scale studies to confirm the reported rates and cost-effectiveness of routine fungal testing.

Date of Award	31 Dec 2023
Original language	English
Awarding Institution	The University of Manchester
Supervisor	David Denning (Supervisor) & Chris Kosmidis (Supervisor)