A diverse spectrum of mycoses histologically diagnosed in Ghana: Insights from a 10-year retrospective study.

In Ghana, most laboratory diagnoses of severe mycoses are based on histopathology findings due to inadequate availability of serology, culture, and molecular tests. The aim of this study was to evaluate the spectrum of mycoses diagnosed in Ghana. We retrospectively reviewed reports from 2012 to 2021 from three major pathology laboratories in Ghana to identify reports indicating the presence of fungal elements and diagnosis of a mycosis, then extracted demographic, clinical history, site of infection, stain(s), used and diagnosed mycosis details. Over the 10-year period, 107 cases were found. No apparent increasing and decreasing trend in the number of cases per year or in a period was observed. The age range of affected patients was from 4 to 86 years. Special stains for fungi were only used in 22 of 107 (20.6%) of cases. The most frequently affected site was the sino-nasal area (34%). Mycosis type was determined for 58 (54.2%) cases, comprising aspergillosis (21), candidiasis (14), dermatophytosis (6), mucormycosis (3), two cases each of chromoblastomycosis, histoplasmosis, eumycetoma, entomophthoromycosis, sporotrichosis, and Malassezia infection and a single case each of cryptococcosis and deep onychomycosis. Of the 53 (49.5%) cases with presumptive diagnosis data, only seven (13.2%) had a pre-biopsy suspicion of mycosis. There is a wide spectrum of mycoses in Ghana, including endemic mycoses not previously reported. Improving the use of special fungal stains could increase yield and mycoses identification. Laboratory diagnostic capacity needs enhancement to complement histopathology investigations with serology, culture, and molecular methods.

In Ghana, diagnosis of mycoses is mainly based on histopathology findings. To appreciate the varied mycoses diagnosed, we reviewed the reports of major laboratories from 2012 to 2021 and found 107 cases including endemic, rare, and previously unreported cases with fungal stains unusually used.

Frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa: a scoping review.

BACKGROUND: Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death. OBJECTIVE: To determine the frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa. METHODS: We conducted a scoping review of autopsy studies conducted in Africa. DATA SOURCES: PubMed, Scopus, Web of Science, Embase, Google Scholar, and African Journal Online. STUDY ELIGIBILITY CRITERIA: The review encompasses studies published from inception to September 2023, and no language restrictions were imposed during the search process. We included studies that reported histopathological or microbiological evidence for the diagnosis of fungal infections and other pathogens. DATA SYNTHESIS: Data were summarized using descriptive statistics and no meta-analysis was performed. RESULTS: We examined 30 articles reporting studies conducted between 1991 and 2019, encompassing a total of 13 066 HIV-infected decedents across ten African countries. In five studies, the autopsy type was not specified. Among those studies with specified autopsy types, 20 involved complete diagnostic autopsies, whereas 5 were categorized as partial or minimally invasive autopsies. There were 2333 pathogens identified, with 946 (40.5%) being mycobacteria, 856 (36.7%) fungal, 231 (3.8%) viral, 208 (8.9%) parasitic, and 92 (3.9%) bacterial. Of the 856 fungal pathogens identified, 654 (28.0%) were Cryptococcus species, 167 (7.2%) Pneumocystis jirovecii, 16 (0.69%) Histoplasma species, 15 (0.64%) Aspergillus species, and 4 (0.17%) Candida species. Other major non-fungal pathogens identified were cytomegalovirus 172 (7.37%) and Toxoplasma gondii 173 (7.42%). CONCLUSIONS: Invasive fungal infections occur in over one-third of people who succumb to HIV in Africa. In addition to cryptococcosis and Pneumocystis jirovecii pneumonia, integrating other priority fungal pathogen detection and management strategies into the broader framework of HIV care in Africa is recommended. This involves increasing awareness regarding the impact of fungal infections in advanced HIV disease and strengthening diagnostic and treatment capacity.

Diagnostic options for pulmonary fungal diseases in Africa.

Background: Fungal lung diseases are global in distribution and require specific tests for diagnosis. We report a survey of diagnostic service provision in Africa. Methods: A written questionnaire was followed by a video conference call with each respondent(s) and external validation. To disseminate the questionnaire, a snowball sample was used. Results: Data were successfully collected from 50 of 51 African countries with populations >1 million. The questionnaire was completed by respondents affiliated with 72 health facilities. Of these 72 respondents, 33 (45.8%) reported data for the whole country while others reported data for a specific region/province within their country. In the public sector, chest X-ray and computed tomography are performed often in 49 countries (98%) and occasionally in 37 countries (74%), and less often in the private sector. Bronchoscopy and spirometry were done often in 28 countries (56%) and occasionally in 18 countries (36%) in the tertiary health facilities of public sector. The most conducted laboratory diagnostic assay was fungal culture (often or occasionally) in 29 countries (58%). In collaboration with the Africa Centre for Disease Control and Prevention, regional webinars and individual country profiles provided further data validation. Conclusion: This survey has found a huge disparity of diagnostic test capability across the African continent. Some good examples of good diagnostic provision and very high-quality care were seen, but this was unusual. The unavailability of essential testing such as spirometry was noted, which has a high impact in the diagnosis of lung diseases. It is important for countries to implement tests based on the World Health Organization Essential Diagnostics List.

Diagnostic capacity for invasive fungal infections in advanced HIV disease in Africa: a continent-wide survey.

BACKGROUND: Fungal infections are common causes of death and morbidity in those with advanced HIV infection. Data on access to diagnostic tests in Africa are scarce. We aimed to evaluate the diagnostic capacity for invasive fungal infections in advanced HIV disease in Africa. METHODS: We did a continent-wide survey by collecting data from 48 of 49 target countries across Africa with a population of more than 1 million; for Lesotho, only information on the provision of cryptococcal antigen testing was obtained. This survey covered 99·65% of the African population. We did the survey in six stages: first, questionnaire development, adaptation, and improvement; second, questionnaire completion by in-country respondents; third, questionnaire review and data analysis followed by video conference calls with respondents; fourth, external validation from public or private sources; fifth, country validation by video conference with senior figures in the Ministry of Health; and sixth, through five regional webinars led by the Africa Centres for Disease Control and Prevention with individual country profiles exchanged by email. Data was compiled and visualised using the Quantum Geographic Information System software and Natural Earth vectors to design maps showing access. FINDINGS: Data were collected between Oct 1, 2020, and Oct 31, 2022 in the 48 target countries. We found that cryptococcal antigen testing is frequently accessible to 358·39 million (25·5%) people in 14 African countries. Over 1031·49 million (73·3%) of 1·4 billion African people have access to a lumbar puncture. India ink microscopy is frequently accessible to 471·03 million (33·5%) people in 23 African countries. About 1041·62 million (74·0%) and 1105·11 million (78·5%) people in Africa do not have access to histoplasmosis and Pneumocystis pneumonia diagnostics in either private or public facilities, respectively. Fungal culture is available in 41 countries covering a population of 1·289 billion (94%) people in Africa. MRI is routinely accessible to 453·59 million (32·2%) people in Africa and occasionally to 390·58 million (27·8%) people. There was a moderate correlation between antiretroviral therapy usage and external expenditure on HIV care (R2=0·42) but almost none between external expenditure and AIDS death rate (R2=0·18), when analysed for 40 African countries. INTERPRETATION: This survey highlights the enormous challenges in the diagnosis of HIV-associated Pneumocystis pneumonia, cryptococcal disease, histoplasmosis, and other fungal infections in Africa. Urgent political and global health leadership could improve the diagnosis of fungal infections in Africa, reducing avoidable deaths. FUNDING: Global Action For Fungal Infections.

Invasive Fungal Diseases in Africa: A Critical Literature Review.

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.

Improving awareness, diagnosis and management of invasive fungal infections in Ghana: establishment of the Ghana Medical Mycology Society.

Invasive fungal infections (IFIs) and medical mycology receive little attention in Ghana. However, the present evolution of biomarker assays for IFIs, offers an opportunity for an increased access to fungal laboratory testing in resource-limited settings, and probably make a case for availability of essential antifungal agents. Using surveys and personal communications, the state of medical mycology and IFI in Ghana were highlighted. Inadequate awareness and insufficient access to fungal diagnostics and therapeutics were identified as the key challenges, the establishment of the Ghana Medical Mycology Society was discussed, and recommendations were made to improve the status quo.

Invasive fungal infections (IFIs) receive little attention in Ghana, despite its growing relevance globally. Using surveys and personal communications, the main challenges were identified, and the formation of the Ghana Medical Mycology Society was discussed as a tool to improve the status quo.

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.

Cryptococcal and Histoplasma Antigen Screening Among People With Human Immunodeficiency Virus in Ghana and Comparative Analysis of OIDx Histoplasma Lateral Flow Assay and IMMY Histoplasma Enzyme Immunoassay.

Background: Cryptococcal meningitis (CM) and disseminated histoplasmosis (DH) are common in people with human immunodeficiency virus (PWH) and diagnosed by detecting cryptococcal antigen (CrAg) and Histoplasma antigen (HistoAg), respectively. In Ghana, CM and DH are rarely suspected by clinicians due to limited epidemiological data. Methods: This study was conducted among PWH in Ghana who are unwell. Sociodemographic and clinical data were collected by questionnaire. Serum and/or urine were screened for CrAg and HistoAg, using IMMY CrAg lateral flow assay (LFA) and IMMY Histoplasma enzyme immunoassay (EIA) kits, respectively, regardless of symptoms. Samples run with IMMY Histoplasma EIA were simultaneously run with Optimum Imaging Diagnostics (OIDx) Histoplasma LFA. Laboratory investigations were conducted by the research team, and diagnosis incorporating clinical assessment, screening, and confirmatory testing results and treatment decisions were made by the clinical team. Treatment and outcome information on CM and DH patients were evaluated. Results: Overall, 150 participants were recruited. There were 73% (n = 109) females, and the age range was 18-62 years. The prevalence rates of CrAg and HistoAg were 2.7% (4 of 150) and 4.7% (5 of 107), respectively. The OIDx Histoplasma LFA showed a high concordance (98.4%) with the IMMY Histoplasma EIA. All antigen-positive cases by standard tests were diagnosed with CM and DH. Antifungal treatment was given in 5 patients and follow-up revealed 2 deaths and 3 recoveries. Conclusions: Histoplasmosis among PWH may be more common than previously anticipated and may be more frequent than cryptococcosis in Ghana. The performance of the OIDx Histoplasma LFA should be further explored.

The current state of clinical mycology in Africa: a European Confederation of Medical Mycology and International Society for Human and Animal Mycology survey.

Africa, although not unique in this context, is a favourable environment for fungal infections, given the high burden of risk factors. An online survey was developed asking about laboratory infrastructure and antifungal drug availability. We received 40 responses (24·4% response rate) of 164 researchers contacted from 21 African countries. Only five institutions (12·5%) of 40 located in Cameroon, Kenya, Nigeria, Sudan, and Uganda potentially fulfilled the minimum laboratory requirements for European Confederation of Medical Mycology Excellence Centre blue status. Difficulties included low access to susceptibility testing for both yeasts and moulds (available in only 30% of institutions) and Aspergillus spp antigen detection (available in only 47·5% of institutions as an in-house or outsourced test), as well as access to mould-active antifungal drugs such as amphotericin B deoxycholate (available for 52·5% of institutions), itraconazole (52·5%), voriconazole (35·0%), and posaconazole (5·0%). United and targeted efforts are crucial to face the growing challenges in clinical mycology.

Histoplasmosis in Africa: Current perspectives, knowledge gaps, and research priorities.

BACKGROUND: Histoplasmosis is a chronic granulomatous disease caused by the thermally dimorphic fungus Histoplasma capsulatum. The 2 variants Histoplasma capsulatum var. capsulatum (Hcc) and Histoplasma capsulatum var. duboisii (Hcd) causes infection in humans and commonly termed classical or American histoplasmosis and African histoplasmosis, respectively. Histoplasma capsulatum var. farciminosum (Hcf) affects equines. In recent times, there have been heightened sensitization on fungal infections such as histoplasmosis in Africa, aimed at improving awareness among relevant stakeholders, particularly healthcare workers. This effort is expected to be paralleled with increased detection of both classical and African histoplasmosis, which has remained underdiagnosed over the years. In this narrative review, we describe the current perspectives of histoplasmosis in Africa, identify knowledge gaps, and suggest research priorities. METHODS: A PubMed, Google Scholar, and Africa Journal Online (AJOL) literature search was conducted for studies on histoplasmosis in Africa between 2000 and 2020. Histoplasmosis essays in medical mycology textbooks were also consulted. This narrative review was prepared from the data gathered. FINDINGS: In the past 2 decades, histoplasmosis in general has seen a relative increase in case detection in some Africa countries, probably attributable to the gradually increasing medical mycology advocacy efforts in Africa. Histoplasmosis cases are dominated by African histoplasmosis mostly in Western and Central Africa, while classical histoplasmosis is more common in Southern and Northern Africa. Although both classical and African histoplasmosis are common in Africa, the latter is more restricted to Africa, and cases outside the continent usually have a travel history to the continent. Despite the clinical and laboratory difference between African histoplasmosis and classical histoplasmosis, it is not straightforward to distinguish them. The typical manifestation of African histoplasmosis is the appearance of lesions affecting the skin, bones, and lymph nodes and unusually linked to human immunodeficiency virus (HIV)/AIDS. By contrast, classical histoplasmosis mostly affects the lungs and is often associated with immunosuppression, mainly HIV/AIDS. The present perspectives of histoplasmosis in Africa highlight unclear details on the true burden, strain diversity, infection route and genetic basis of African histoplasmosis, availability of specie-specific diagnostic tools, and compliance with recommended antifungal therapy. These knowledge gaps represent research questions that require scientific exploration. CONCLUSIONS: Despite a subtle increase in identifying histoplasmosis cases in Africa, it remains underdiagnosed and neglected in some parts of the continent. Increasing awareness and training among healthcare workers, bridging diagnostic and therapeutic gaps, and encouraging more research in Africa are crucial to improve the current perspectives of histoplasmosis in Africa.

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.

Importance of Aspergillus-Specific Antibody Screening for Diagnosis of Chronic Pulmonary Aspergillosis after Tuberculosis Treatment: A Prospective Follow-Up Study in Ghana.

Chronic pulmonary aspergillosis (CPA) often occurs in patients that have been previously treated for pulmonary tuberculosis (PTB). A limited number of studies have looked at the development of CPA at different times following the completion of a PTB treatment course. This prospective longitudinal study aimed to determine the incidence of CPA at two timepoints, at the end of the PTB treatment (T1) and six months post-treatment (T2). Patients with confirmed PTB from a previous study who were placed on anti-TB medication were followed up and screened for CPA at T1 and T2 by assessing their symptoms, evaluating their quality of life, and screening them for Aspergillus infection by performing antibody testing and cultures. CPA was defined by the Global Action for Fungal Infections (GAFFI) diagnostic algorithm. Forty-one patients were enrolled, of whom thirty-three patients (80%) and twenty-eight patients (68%) were resurveyed at T1 and T2, respectively. The rate of new CPA was 3.3% (1/33) and 7.4% (2/27) at T1 and T2, respectively, with an overall incidence of 10.7% (3/28) among the patients at both T1 and T2. A positive Aspergillus-specific antibody test was an indicator for CPA in all three patients. Aspergillus-specific antibody screening during and after the end of an anti-TB treatment regimen may be important for early detection of CPA in high-PTB-burden settings.

Estimated burden of serious fungal infections in Togo.

BACKGROUND: Over the years, the focus of infectious diseases in many African countries has been mainly on viral, bacterial and parasitic infections. Serious fungal infections (SFIs) with comparable morbidity rate in these countries remain neglected. OBJECTIVES: To estimate the burden of SFI in Togo and to stimulate efforts for improved attention. METHODS: Literature was thoroughly searched for epidemiological data on SFI in Togo. Incidence and/or prevalence of SFI was estimated using socio-demographics, health system's information, risk-groups data and SFI rates obtained from national and international studies. RESULTS: About 5.29% of the 7,265,286 Togolese population is estimated to suffer from SFI annually. Among HIV patients, 1,342, 1,650 and 330 may develop cryptococcal meningitis, Pneumocystis pneumonia and disseminated histoplasmosis respectively per year. Oral and oesophageal candidiasis may annually affect 19,800 and 7,535 persons, respectively, living with HIV. Estimated incidence of invasive aspergillosis (IA) was 283 cases. Prevalence of chronic pulmonary aspergillosis (CPA) was estimated at 191 cases. The annual incidence of allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) was 4,577 and 6,042 cases, respectively. Tinea capitis and recurrent Candida vaginitis presumably affect 232,271 children and 108,979 women respectively. Candidaemia incidence is estimated at 5 cases per 100, 000 inhabitants and fungal keratitis may affect 981 persons annually. CONCLUSIONS: SFIs in Togo are probably more significant than expected. These findings underscore the need to increase awareness among healthcare professionals, enhance diagnostic and therapeutic capacities and intensify epidemiological studies for effective management of fungal infections in Togo.

Mycetoma in West Africa.

BACKGROUND: Mycetoma is a neglected disease, which is socioeconomically important, and with the possibility of permanent disability in infected persons if not treated early. This is especially true in resource-limited settings such as West Africa, where there is a lack of facilities and skilled personnel to make a definitive laboratory diagnosis. Countries in West Africa have similar climatic conditions to Sudan. The majority of patients seek medical care very late, when there is already bone involvement, resulting in amputations. This results in poor capture of the true burden of the problem in the literature. METHODS: A review of the literature revealed about 2685 documented cases in West Africa from 1929 to 2020; from 15 out of 16 countries, Senegal accounted for 74.1% (1943) of cases in the subregion. RESULTS: The majority of lesions were found on the foot; however, other body parts were also reported. Rural dwellers accounted for most cases. Only 547 (20.4%) cases had identified isolates reported. Actinomycetoma accounted for 47.9% of cases, eumycetoma 39.7% and unidentified pathogens 12.4%. Actinomadura pelletieri was the predominant pathogen isolated (21.4%; 117 isolates). CONCLUSION: There is a dire need for capacity building, provision of facility and health education to raise awareness of this debilitating disease in West Africa.

Estimated Burden of Serious Fungal Infections in Ghana.

Fungal infections are increasingly becoming common and yet often neglected in developing countries. Information on the burden of these infections is important for improved patient outcomes. The burden of serious fungal infections in Ghana is unknown. We aimed to estimate this burden. Using local, regional, or global data and estimates of population and at-risk groups, deterministic modelling was employed to estimate national incidence or prevalence. Our study revealed that about 4% of Ghanaians suffer from serious fungal infections yearly, with over 35,000 affected by life-threatening invasive fungal infections. Incidence of cryptococcal meningitis, Pneumocystis jirovecii pneumonia, and disseminated histoplasmosis cases in AIDS was estimated at 6275, 12,610 and 724, respectively. Oral and esophageal candidiasis collectively affect 27,100 Ghanaians and 42,653 adult asthmatics are estimated to have fungal asthma. We estimate a prevalence of 12,620 cases of chronic pulmonary aspergillosis (CPA and an incidence of 1254 cases of invasive aspergillosis (IA). Estimated cases of candidemia and candida peritonitis cases were 1446 and 217, respectively. The estimated prevalence of recurrent vulvovaginal candidiasis (RVVC) and tinea capitis was 442,621 and 598,840, respectively. Mucormycosis and fungal keratitis each may affect 58 and 810 Ghanaians. These data highlight the urgent need for intensified awareness to improve diagnosis and management.