Striving towards access to essential medicines for human and animal health; a situational analysis of access to and use of antifungal medications for histoplasmosis in Ethiopia.

Antifungal medications are vital in combatting fungal diseases that affect over a billion people annually. Antifungal medications for people and equids are scarce in Ethiopia, where lack of resources to treat fungal infection, in particular histoplasmosis, is a major health challenge. Histoplasmosis is endemic within the equine population in Ethiopia, where it is estimated that one in five horses are infected. This disease has far reaching impacts on equine welfare and the socio-economic wellbeing of families. The burden of histoplasmosis in people in Ethiopia is currently unknown, representing a blind spot in public health surveillance. Previous research has identified contact with wildlife, and domestic animal species as possible transmission pathways for histoplasmosis however, questions remain about the role of equids in human histoplasmosis. Given the close proximity of people and animals in this setting, the high level of endemic disease among equids, and the common sources of anti-fungals in Ethiopia, our study adopted a One-Health approach to examine how systemic issues affect access to, and use of antifungals to treat histoplasmosis among people and equids. A qualitative study was conducted in 6 urban regions of Oromia, Ethiopia in December 2018, incorporating semi-structured face-to-face interviews and focus group discussions. Twenty-seven individual interviews were held with doctors (n = 7), pharmacists (n = 12), veterinarians (n = 5), para-veterinarians (n = 2) and an equid owner (n = 1). Eleven focus groups were conducted with equid owners (n = 42), 3 with veterinarians (n = 6), 1 with para-veterinarians (n = 2) and 1 with pharmacists (n = 2). Transcripts were analysed using thematic analysis, and dimensions of key themes conceptualised and compared. Two overarching themes namely, 'Structural', and 'Human factors', summarised the main limitations to access to antifungal medications. 'Structural factors' included the national reliance on importation of medicines or pharmaceutical ingredients, inaccurate demand forecasting due to poor recording of the shortfall within the pharmaceutical supply chain, deficiencies in diagnostic capacity for fungal disease and, a healthcare system funded with a significant component of out-of-pocket expenditure. 'Human factors' that influenced access to antifungals included the perception of the expense of antifungals compared with competing needs such as food and education, the social stigma attached to histoplasmosis that could lead to delays in treatment seeking and, readily available home remedies or alternative treatment options. Furthermore, it was reported that trust in healthcare and veterinary provisions was undermined by a perceived lack of efficacious medications. Access to antifungals remains an urgent public health and animal welfare concern in Ethiopia. Key points within the supply and distribution chain that affect access to anti-fungals are identified, and policies that facilitate anti-fungal procurement and distribution should be reviewed. This paper highlights the structural, socio-economic and cultural factors influencing the management of infection with histoplasmosis, including how it is understood, identified and treated. This study identifies areas where further cross-sectorial work is needed to address these factors to improve disease control and clinical outcomes observed in human and animal histoplasmosis within Ethiopia.

Paracoccidioides spp. and Histoplasma capsulatum: Current and New Perspectives for Diagnosis and Treatment.

The thermally-dimorphic systemic fungal group includes several important human pathogens: Blastomyces dermatitides, Coccidioides immitis and C. posadasii, Histoplasma capsulatum, Paracoccidioides brasiliensis, P. lutzii, and Talaromyces (Penicillium) marneffei. They usually are geographically restricted and have natural habitats in soil or in plants, and when fungal propagules invade mammalian host by inhalation, they initiate an inflammatory reaction that can result in self-resolution of the infection or cause an acute or chronic disease. In the setting of the AIDS pandemic and the developments in modern medicine, such as immunosuppressive therapy in cancer surgery patients and in transplantation and autoimmune diseases, the incidence of endemic mycoses has progressively increased. Another important factor of the increased incidence of systemic mycoses in certain regions is the progressive devastation of tropical and subtropical forests. In this review, we focus on two of the most important systemic mycoses: paracoccidioidomycosis and histoplasmosis, and their major characteristics in epidemiology, clinical aspects and laboratorial diagnosis.

Etiologies of illness among patients meeting integrated management of adolescent and adult illness district clinician manual criteria for severe infections in northern Tanzania: implications for empiric antimicrobial therapy.

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.

Histoplasmosis in HIV-positive patients in Ceará, Brazil: clinical-laboratory aspects and in vitro antifungal susceptibility of Histoplasma capsulatum isolates.

This study contains a descriptive analysis of histoplasmosis in AIDS patients between 2006 and 2010 in the state of Ceará, Brazil. Additionally, the in vitro susceptibility of Histoplasma capsulatum isolates obtained during this period was assessed. We report 208 cases of patients with histoplasmosis and AIDS, describing the epidemiological, clinical, laboratory and therapeutic aspects. The in vitro antifungal susceptibility test was carried out by the microdilution method, according to Clinical and Laboratory Standards Institute, with H. capsulatum in the filamentous and yeast phases, against the antifungals amphotericin B, fluconazole, itraconazole, voriconazole and caspofungin. In 38.9% of the cases, histoplasmosis was the first indicator of AIDS and in 85.8% of the patients the CD4 cell count was lower than 100 cells/mm(3). The lactate dehydrogenase levels were high in all the patients evaluated, with impairment of hepatic and renal function and evolution to death in 42.3% of the cases. The in vitro susceptibility profile demonstrated there was no antifungal resistance among the isolates evaluated. There was a significant increase in the number of histoplasmosis cases in HIV-positive patients during the period surveyed in the state of Ceará, northeastern Brazil, but no antifungal resistance among the recovered isolates of H. capsulatum.

An unusual cutaneous tumor: African histoplasmosis following mudbaths: case report and review.

African histoplasmosis, caused by Histoplasma capsulatum var. duboisii, is endemic in Africa. The disease usually involves the skin, subcutaneous tissue, and bones. A case of African histoplasmosis presenting as a cutaneous tumor and non-healing wound in a 66-year-old immunocompetent male residing in Africa, the first ever reported following mudbaths and acupuncture, is hereby reported. Diagnosis was confirmed by means of polymerase chain reaction performed on tissue material. The patient was started on long-term itraconazole therapy and he responded well. African histoplasmosis should be included in the differential diagnosis of non-healing wounds or tumor-like lesions, especially in the context of mudbaths in an endemic area.