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

Gastrointestinal Histoplasmosis: A Descriptive Review, 2001–2021

Gastrointestinal histoplasmosis (GIH) is infrequently described in people without underlying HIV infection. We aimed to compare the clinical presentation of GIH in people with and without HIV infection. We conducted a literature search of published cases of GIH from 2001–2021 and found 212 cases. Of these, 142 (67.0%) were male, and 124 (58.5%) had HIV infection. Most cases were from North America (n = 88, 41.5%) and South America (n = 79, 37.3%). Of the 212 cases, 123 (58.0%) were included in both clinical and pathological analyses. The remainder were excluded as details about clinical and pathological findings were not available. Of the 123 cases, 41 had HIV infection while 82 were without HIV infection. The diagnosis was predominantly by histopathology (n = 109, 88.6%). A significant proportion of people with HIV infection had abdominal pain as the most predominant symptom of GIH compared to those without HIV infection (65.9% versus 41.9%, p < 0.05). The colon was the most affected site with a slightly higher proportion in those with HIV infection compared with cases without HIV infection (46.3% versus 42.7%). The commonest pathologic findings were caecal and ileal ulcers. Caecal ulcers were significantly more frequent in cases with HIV infection compared to those without HIV (32.1% versus 7.1%, p < 0.05). Despite being more common in people with HIV infection, GIH also affects people without HIV infection with similar clinical presentations

Histoplasmosis in Children; HIV/AIDS Not a Major Driver

The classification of histoplasmosis as an AIDS-defining illness has largely attributed its occurrence in people to the presence of HIV/AIDS especially in Africa. Prior to the advent of the HIV/AIDS epidemic, several cases of histoplasmosis were documented both in the pediatric and adult populations. Our review revealed 1461 reported cases of pediatric histoplasmosis globally in the last eight decades (1939-2021). North America (n = 1231) had the highest number of cases, followed by South America (n = 135), Africa (n = 65), Asia (n = 26) and Europe (n = 4). Histoplasmosis was much more common in the non-HIV pediatric population (n = 1418, 97.1%) compared to the HIV population. The non-HIV factors implicated were, childhood malignancies (n = 207), such as leukemias and lymphomas as well as their treatment, lung diseases (n = 7), environmental exposures and toxins (n = 224), autoimmune diseases (n = 12), organ transplants (n = 12), long-term steroid therapy (n = 3), the use of immunosuppressive drugs such as TNF-alpha inhibitors (n = 7) malnutrition (n = 12), histiocytosis (n = 3), Hyper immunoglobulin M and E syndromes (n = 15, 1.2%), pancytopenia (n = 26), diabetes mellitus (n = 1) and T-cell deficiency (n = 21). Paediatricians should always consider or rule out a diagnosis of histoplasmosis in children presenting with symptoms suggestive of the above clinical conditions.</p

Fungal contamination of the water distribution system of a tertiary hospital water supply system in a resource-limited setting

Background: Fungal contamination of hospital water distribution systems has been implicated in outbreaks of healthcare-associated infections. Objectives: To evaluate the prevalence of fungi in the water distribution system of a tertiary hospital in Nigeria. Design: This was a descriptive cross-sectional study. Methods: Swabs and water samples were collected from taps and faucets in the hospital categorized into low (Accidents and Emergency Unit, Children Emergency Unit, Acute Stroke Unit and the 24 in-patient hospital wards) and high-risk (Renal Dialysis Unit, Central Sterile Services Department, Theatres and Intensive Care Units (ICUs)) units based on the vulnerability of patients being managed there. The membrane filtration method for water analysis was used. Where possible, isolates cultured were identified to species level. In total, 105 water and 49 swab samples were collected for analysis. Results: All analysed water samples grew fungi. A total of 289 (high-risk; n  = 178; low-risk; n  = 111) and 76 fungi isolates were recorded from water and swab samples, respectively, with 31 different species identified. Aspergillus was the most predominant genus with five different species: Aspergillus niger (9.9%), terreus (4.4%), flavus (3.3%), fumigatus (8.8%) and versicolor (2.20%) isolated. Twenty-five and 18 species of fungi were identified in the low and high-risk units, respectively. The labour ward ( n  = 46; 25.8%) and modular theatre ( n  = 47; 42.3%) were the most contaminated units. Cladosporium spp. and Paecilomyces spp. were the most frequently isolated fungi in the low and high-risk units, respectively. The dialysis centre ( n  = 9; 8.1%) and renal transplant theatre ( n  = 7; 6.31%) had the lowest contamination rates in the high-risk units. Aspergillus niger , Cephalosporium curtipes , Penicillium chrysogenum and Penicillium glabrum were each identified in 4/6 units from which swabs were taken. The facility had no documented protocol for its water safety and quality. Conclusion: Our data reveal a high rate of contamination of hospital water sources by fungi, some of which are known to cause life-threatening infections. For better water treatment and water tank cleaning and disinfection, a standard protocol is advised. Ensuring that the water distribution systems in hospital settings are free of fungal contaminants is important to prevent the possibility of waterborne mycosis outbreaks

Histoplasmosis in Children; HIV/AIDS Not a Major Driver

The classification of histoplasmosis as an AIDS-defining illness has largely attributed its occurrence in people to the presence of HIV/AIDS especially in Africa. Prior to the advent of the HIV/AIDS epidemic, many cases of histoplasmosis were documented both in the pediatric and adult population. Our review revealed 1461 reported cases of pediatric histoplasmosis globally in the last eight decades (1939–2021). North America (n = 1231) had the highest number of cases, followed by South America (n = 135), Africa (n = 65), Asia (n = 26) and Europe (n = 4). Histoplasmosis was much more common in the non-HIV pediatric population (n = 1418, 97.1%) compared to the HIV population. The non-HIV factors implicated were, childhood malignancies (n = 207), such as leukemias and lymphomas as well as their treatment, lung diseases (n = 7), environmental exposures and toxins (n = 224), autoimmune diseases (n = 12), organ transplants (n = 12), long-term steroid therapy (n = 3), the use of immunosuppressive drugs such as TNF-alpha inhibitors (n = 7) malnutrition (n = 12), histiocytosis (n = 3), hyperimmunoglobulin M and E syndromes (n = 15, 1.2%), pancytopaenias (n = 26), diabetes mellitus (n = 1) and T-cell deficiency (n = 21). Paediatricians should always consider or rule out a diagnosis of histoplasmosis in children presenting with symptoms suggestive of the above clinical conditions

Pulmonary and Extrapulmonary Manifestations of Fungal Infections Misdiagnosed as Tuberculosis: The Need for Prompt Diagnosis and Management

Fungal infections commonly present with myriad symptoms that mimic other clinical entities, notable amongst which is tuberculosis. Besides histoplasmosis and chronic pulmonary aspergillosis, which can mimic TB, this review has identified several other fungal infections which also do. A total of 80 individual cases misdiagnosed as TB are highlighted: aspergillosis (n = 18, 22.5%), histoplasmosis (n = 16, 20%), blastomycosis (n = 14, 17.5%), cryptococcosis (n = 11, 13.8%), talaromycosis (n = 7, 8.8%), coccidioidomycosis (n = 5, 6.3%), mucormycosis (n = 4, 5%), sporotrichosis (n = 3, 3.8%), phaeohyphomycosis (n = 1, 1.3%) and chromoblastomycosis (n = 1, 1.3%). Case series from India and Pakistan reported over 100 cases of chronic and allergic bronchopulmonary aspergillosis had received anti-TB therapy before the correct diagnosis was made. Forty-five cases (56.3%) had favorable outcomes, and 25 (33.8%) died, outcome was unclear in the remainder. Seventeen (21.3%) cases were infected with human immunodeficiency virus (HIV). Diagnostic modalities were histopathology (n = 46, 57.5%), culture (n = 42, 52.5%), serology (n = 18, 22.5%), cytology (n = 2, 2.5%), gene sequencing (n = 5, 6.3%) and microscopy (n = 10, 12.5%) including Gram stain, India ink preparation, bone marrow smear and KOH mount. We conclude that the above fungal infections should always be considered or ruled out whenever a patient presents with symptoms suggestive of tuberculosis which is unconfirmed thereby reducing prolonged hospital stay and mortalities associated with a delayed or incorrect diagnosis of fungal infections

Isolated renal and urinary tract aspergillosis: a systematic review

Background: Aspergillosis localized to the kidneys and the urinary tract is uncommon. We conducted a comprehensive systematic review to evaluate risk factors and clinical outcomes of patients with isolated renal and genito-urinary tract aspergillosis. Methods: We systematically searched Medline, CINAHL, Embase, African Journal Online, Google Scholar, and the Cochrane Library, covering the period from inception to August 2023 using the key terms ‘renal’ OR ‘kidney*’ OR ‘prostate’ OR ‘urinary bladder’ OR ‘urinary tract*AND ‘aspergillosis’ OR ‘aspergillus’ OR ‘aspergilloma’ OR ‘mycetoma’. We included single case reports or case series. Review articles, guidelines, meta-analyses, animal studies, protocols, and cases of genitourinary and /or renal aspergillosis occurring as a part of disseminated disease were excluded. Results: We identified 91 renal and urinary aspergillosis cases extracted from 76 publications spanning 1925–2023. Among the participants, 79 (86.8%) were male, with a median age of 46 years. Predominantly, presentations consisted of isolated renal infections (74 instances, 81.3%), followed by prostate (5 cases, 5.5%), and bladder (7 cases, 7.7%) involvement. Aspergillus fumigatus (42.9%), Aspergillus flavus (9.9%), and Aspergillus niger/glaucus (1.1% each) were isolated. Underlying risk factors included diabetes mellitus (29.7%), HIV (12.1%), haematological malignancies (11%), and liver cirrhosis (8.8%), while common symptoms encompassed flank pain (36.3%), fever (33%), and lower urinary tract symptoms (20.9%). An autopsy was conducted in 8.8% of cases. Diagnostic work-up involved histopathology (70.5%), renal CT scans and urine microscopy and culture (52.6% each), and abdominal ultrasound (17.9%). Treatments included amphotericin B (34 cases, 37.4%) and azole-based regimens (29 cases, 31.9%). Nephrectomy was performed in 16 of 78 renal cases (20.5%). All-cause mortality was 24.4% (19 cases). No significant mortality rate difference was observed among antifungal regimens ( p  = 0.739) or nephrectomy status ( p  = 0.8). Conclusion: Renal and urinary aspergillosis is an important cause of morbidity and mortality, particularly in immunocompromised and people with diabetes mellitus. While varied treatment strategies were observed, mortality rates showed no significant differences based on treatments or nephrectomy status. Further research is needed to refine diagnostics, optimize treatments, and enhance awareness among clinicians for early detection and management. PROSPERO registration number: CRD42023430959

Prevalence of Histoplasmosis among Persons with Advanced HIV Disease, Nigeria

We sought to determine the prevalence of probable disseminated histoplasmosis among advanced HIV disease (AHD) patients in Nigeria. We conducted a cross-sectional study in 10 sites across 5 of 6 geopolitical zones in Nigeria. We identified patients with urinary samples containing CD4 cell counts &lt;200 cells/mm3 or World Health Organization stage 3 or 4 disease who also had &gt;2 clinical features of disseminated histoplasmosis, and we tested them for Histoplasma antigen using a Histoplasma enzyme immune assay. Of 988 participants we recruited, 76 (7.7%) were antigen-positive. The 76 Histoplasma antigen-positive participants had significantly lower (p = 0.03) CD4 counts; 9 (11.8%) were also co-infected with tuberculosis. Most antigen-positive participants (50/76; 65.8%; p = 0.015) had previously received antiretroviral treatment; 26/76 (34.2%) had not. Because histoplasmosis is often a hidden disease among AHD patients in Nigeria, Histoplasma antigen testing should be required in the AHD package of care.</p