Histoplasmosis

1. Histoplasmosis Disseminated histoplasmosis in an African pygmy hedgehog JAVMA232(1) (Jan. 1, 2008): 74-76 Review for ACVPM by CPT Shannon Lacy

2. Agent Characteristics • Histoplasma capsulatum • Dimorphic fungus, meaning its saprophytic and parasitic phases differ morphologically Yeast phase (in animals): yeast form consists of oval, singly budding cells (bottom image is a silver stain to highlight the organisms). Mycelial phase (free-living): consists of septate hyphae bearing spherical microconidia and “tuberculate” macroconidia

3. Agent Characteristics cont. • One of the systemic or “deep” mycoses • Others: Coccidiodes, Blastomyces • Notes about systemic mycoses: • Most are caused by dimorphic fungi • Infection is usually via inhalation • Host factors are often decisive disease determinants • Lesions tend to be pyogranulomatous • Although the agent is often shed, systemic mycoses are generally not contagious

4. Agent Characteristics cont. • A few more systemic mycosis generalizations:

5. Back to Histoplasma…Species Affected • Humans, dogs, cats • Rare – cattle, horses, swine, wildlife • Very rare – African Pygmy Hedgehog! (see report) • A saprozoonosis, meaning it has a non-animal reservoir (soil) • Direct animal-to-human transmission is not believed to happen • Animals may serve as sentinels for human infection

6. Clinical Signs • In dogs and cats, seen most commonly in young animals (<4yr) • Short incubation period (12-16 d) • Infection via inhalation, but rapid dissemination is common • Dog: GI signs (large bowel diarrhea, inappetence, fever, weightloss) most common in dogs due to granulomatous colitis; ocular and bone lesions less common • Cat: respiratory and systemic involvement, course is usually insidious

7. Clinical Signs cont. • Humans: • Acute or chronic pulmonary disease • Mediastinal granulomatiosis • Adrenal insufficiency – Addisonian crisis • CNS disease • Chorioretinitis • Cutaneous lesions • Ulcerative glossitis in immunocompromised

8. Diagnosis • Dogs – cytology of rectal scrapings / colonic biopsies • Organism commonly within macrophages • Serologic tests are often falely negative • Urine antigen test in humans

9. Treatment • Itraconazole or Ketoconazole • With food (better absorption w/ low pH) • Does NOT reach CNS because is highly protein bound • Side effects w/ ketoconazole – hepatotoxic • Fluconazole – penetrates CNS and eye • Amphotericin B • Serious side effects • Reserved for cases unresponsive to azoles

10. JAVMA Case Report:Disseminated histoplasmosis in an African pygmy hedgehog • 2yo intact captive-bred Atelerix albivenris • 4-day Hx of inappentence, weakness, leth. • No dx on initial presentation; treated for occult parasitic infestation and possible bacterial infection • 1 week later, mild improvement • Another week later, relapse of original signs, plus low body temperature

11. Disseminated histoplasmosis in an African pygmy hedgehog cont’d. • Palpably enlarged spleen • Hospitalized – Baytril, supportive care… • Died. • Necropsy – severe splenomegaly, mild hepatomegaly • Histopathology revealed H. capsulatum var. capsulatum in spleen, liver, kidney, SI, heart, stomach, and lungs

12. Disseminated histoplasmosis in an African pygmy hedgehog cont’d. • Highlights from the “Discussion” • List of species previously reported affected: • Human, dog, cat, horse, pig, cattle • Domestic rodents, skunks, woodchucks, raccoons, baboons, Kodiak bears, badgers, fox, llamas, rabbits, chinchillas, owl monkeys, rhesus, Atlantic bottlenose dolphins, sea otters, harp seals, mara, Fennec foxes. • This is the first known report in a hedgehog

13. Disseminated histoplasmosis in an African pygmy hedgehog cont’d. • Highlights from the “Discussion” • Histoplasmosis results from inhalation of Ajellomyces capsulatum, the teleomorph of H. capsulatum var capsulatum • Note, teleomorph just means the mycelial (vs. yeast) phase of the organism • Converts to yeast form in lung, resulting in pulmonary infection, which often goes undetected • Dissemination to lymphoid tissues and liver is rapid

14. Disseminated histoplasmosis in an African pygmy hedgehog cont’d. • Highlights from the “Discussion” • Additional diagnostic methods: buffy coat smear, bone marrow aspirates • Antigen test used in humans has not been validated in other species • How did an indoor hedgehog get histoplasmosis??? • Speculate dust from outside, as this pet lived in an endemic region of OK • Or, contaminated bedding? Has been incriminated in other reports

15. Disseminated histoplasmosis in an African pygmy hedgehog cont’d. • Highlights from the “Discussion” • Other zoonoses from hedgehogs include the pathogenic dermatophytes and Salmonella spp. • Note, H. capsulatum is a saprozoonosis, but could be transmitted to humans during handling laboratory culture specimens or during a necropsy

16. References • Snider, T.A., Joyner, P.H., & Clinkenbeard, K.D. (2008). Disseminted histoplasmosis in an African pygmy hedgehog. JAVMA 232(1): 74-76. • Olsen, C.W. (2008). Zoonotic disease tutorial. Online at http://www.vetmed.wisc.edu/pbs/zoonoses/