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.

Diagnosing disseminated histoplasmosis in advanced HIV/AIDS disease in Cameroon using a point of care lateral flow assay.

Histoplasmosis is an AIDS-defining opportunistic infection. Disseminated histoplasmosis (DH) can be fatal without early diagnosis and treatment initiation. We present one confirmed and three probable cases of DH in advanced HIV/AIDS disease patients diagnosed using OIDx Histoplasma LFA in Yaoundé, Cameroon. Four women with HIV but unknown CD4 count presented with asthenia, weight loss, productive cough, and fever (39°C) as common symptoms for at least 3 weeks. Two of the patients had skin lesions. These included facial papules, macules, and umbilicated vesicles scattered over the trunk and limbs. These were diffuse lesions which were purulent, itching, and papillomatous lesions with a necrotic centre, and one patient had a right forearm ulcer. We performed the Histoplasma antigen tests using the OIDx Histo LFA, and they were strongly positive in all four patients. Histopathology in skin biopsy allowed identification of the species as Histoplasma capsulatum var capsulatum in one patient. In this same patient, Pseudomonas aeruginosa and Proteus mirabilis were cultured from the forearm ulcer. This patient later commenced antibiotics (Levofloxacin 500 mg) and oral itraconazole (800 mg/day) with immediate improvement. Unfortunately, the other three patients could not access itraconazole, were discharged and lost to follow-up. Early diagnosis and treatment are essential for the management of DH. LFA is a test that can be set up in any setting with limited resource. Access to this can be a major advance in the diagnosis of histoplasmosis in resource-limited settings.

Histoplasmosis overlapping with HIV and tuberculosis in sub-Saharan Africa: challenges and research priorities.

Histoplasmosis, tuberculosis and HIV are all highly prevalent in sub-Saharan Africa (SSA). Co-occurrence of two or more of these infections has been reported in several populations of patients, especially those with advanced HIV infection where these opportunistic infections contribute to a significant morbidity and mortality. With a high burden of pulmonary tuberculosis (PTB) secondary to HIV in SSA, histoplasmosis is commonly misdiagnosed as smear-negative PTB in HIV patients due to similar clinical and radiological presentations. This is also partly the result of the lack of trained clinical and laboratory personnel to make a definite diagnosis of histoplasmosis. There is a low index of clinical suspicion for histoplasmosis, and cases are mostly discovered accidently and documented through case reports and case series. Similarly, the high cost and lack of fungal diagnostics in most SSA countries makes it difficult to make a diagnosis. There is a need to build local capacity for mycology so that patients are managed to improve on the index of clinical suspicion and diagnostic capabilities. Moreover, simple accurate point-of-care diagnostic tests and first-line antifungal treatment for histoplasmosis are not available in many SSA countries. This review describes the existence of co-infections of histoplasmosis, tuberculosis and HIV in SSA, highlighting the challenges and research priorities.