Histoplasmosis in African children: clinical features, diagnosis and treatment

Abstract

Most of the reviews on histoplasmosis documented in literature have been in the adult population. Very few studies highlight the peculiarities associated with histoplasmosis in Africa especially in the pediatric population. This review addresses the above concerns with clinical summaries and diagnosis of some case reports of histoplasmosis in African children. We highlighted 44 case reports of histoplasmosis in African children (1950–2021) distributed across Western Africa (38.6%, n = 17), Eastern Africa (9.1%, n = 4), Southern Africa (9.1%, n = 4), and Central Africa (43.2%, n = 19). No case report was found from Northern Africa. The age range was 1–17 years, with a mean of 9.2. Of the 44 case reports, 8 cases (18.2%, 8/44) were caused by Histoplasma capsulatum var capsulatum, 33 cases (75%, 33/44) were caused by Histoplasma capsulatum var duboisii, and specie identification was not found in 3 cases. Only three (6.8%) cases were HIV positive; 56.8% (25/44) were disseminated histoplasmosis, pulmonary histoplasmosis accounted for just one case (2.3%, 1/44). Extrapulmonary presentation included skin lesions (ulcers, fistulas, nodules, patches, pigmentations, papules, and abscesses), bone lesions, osteoarthritis, and fractures. The commonest sites affected were skin ( n = 29, 65.9%), bones ( n = 20, 45.5%), and lymph nodes ( n = 15, 34.1%). Histopathology was the commonest diagnostic method ( n = 33, 75%). Amphotericin B was first-line therapy in 45.5% of the cases ( n = 20) followed by ketoconazole (20.5%, n = 9); 27 cases (61.4%) had favorable outcomes, 8 cases (18.2%) had fatal outcomes, while in 9 cases, the outcome was not revealed. This review revealed several cases of histoplasmosis misdiagnosed as other conditions including tuberculosis ( n = 3, 6.8%), pneumonia ( n = 1, 2.3%), cancers ( n = 4, 9.1%), nephritic syndrome ( n = 1, 2.3%), leishmaniasis ( n = 1, 2.3%), and hyperreactive malarial splenomegaly syndrome ( n = 1, 2.3%). In addition, histoplasmosis was not considered in some case reports even when symptoms were suggestive. Diagnosis of histoplasmosis was made at autopsy with postmortem findings suggestive of histoplasmosis ( n = 3, 6.8%). This report highlights the need for a paradigm shift on the part of pediatricians in Africa. They need to look beyond clinical conditions considered common in our environment for this age group and evaluate for other diseases including histoplasmosis.

Prevalence of Histoplasmosis and Molecular Characterization of Histoplasma species in Patients with Presumptive Pulmonary Tuberculosis in Calabar, Nigeria

“…Data on histoplasmosis and TB coinfection in Africa are limited. However, case reports have been documented across all ages [ 2 , 7 ].…”

“…However, in the pediatric population, histoplasmosis is predominantly associated with risk factors other than HIV including environmental exposures and toxins, autoimmune diseases, childhood malignancies as well as their treatment, chronic lung diseases, immunosuppressive therapies, pancytopenia, T-cell deficiency, and malnutrition [ 4 , 5 ]. The diagnosis of histoplasmosis in resource-limited settings like ours is particularly challenging because it mimics TB, a clinical entity that is very common in this region [ 1 , 2 , 5–7 ]. This underscores why histoplasmosis is commonly misdiagnosed as TB in our setting [ 1 , 2 , 7 ], with associated increased mortality, prolonged hospital stays, and unnecessary surgical interventions with attendant financial burden [ 2 , 7 , 8 ].…”

“…The diagnosis of histoplasmosis in resource-limited settings like ours is particularly challenging because it mimics TB, a clinical entity that is very common in this region [ 1 , 2 , 5–7 ]. This underscores why histoplasmosis is commonly misdiagnosed as TB in our setting [ 1 , 2 , 7 ], with associated increased mortality, prolonged hospital stays, and unnecessary surgical interventions with attendant financial burden [ 2 , 7 , 8 ]. The pulmonary and disseminated forms of histoplasmosis present with features including fever, cough, generalized weakness, abdominal pain, abdominal swelling, nocturnal sweating, skin lesions, lymphadenopathy, hepatomegaly, and splenomegaly, which are also seen in all forms of TB [ 2 , 6 ].…”

“…This underscores why histoplasmosis is commonly misdiagnosed as TB in our setting [ 1 , 2 , 7 ], with associated increased mortality, prolonged hospital stays, and unnecessary surgical interventions with attendant financial burden [ 2 , 7 , 8 ]. The pulmonary and disseminated forms of histoplasmosis present with features including fever, cough, generalized weakness, abdominal pain, abdominal swelling, nocturnal sweating, skin lesions, lymphadenopathy, hepatomegaly, and splenomegaly, which are also seen in all forms of TB [ 2 , 6 ]. Oladele et al, in a review study that spanned 6 decades, identified major features common to TB and disseminated histoplasmosis [DH] in the context of HIV infection including immunosuppression, pancytopenia, diarrhea, hepatomegaly, elevated liver enzymes, elevated C-reactive protein, skin lesions, and the involvement of organ systems (gastrointestinal tract, bone marrow, and central nervous system) [ 1 ].…”

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

“…Similarities in the patterns of presentation of invasive fungal infections and TB results in misdiagnosis often associated with increased length of hospital stay, economic loss, increased morbidity and poor clinical outcomes [ 2 ]. Patients in areas endemic for tuberculosis including Africa and Asia are often commenced on anti-TB therapy despite negative microbiological test results including the highly sensitive nucleic acid amplification tests [ 2 , 3 ]. In addition, the true burden of fungal infections especially in resource limited settings has been masked by lack of diagnostic tools giving the impression that they are uncommon compared to well-known conditions such as TB [ 2 ].…”