Medical Mycology (Biol 4849) Summer 2007

Dr. Cooper

Histoplasmosis

Synonyms: African histoplasmosis, Histoplasma capsulatum, Histoplasma duboisii, North American histoplasmosis, Darling disease

• Histoplasmosis

• intracellular myotic infection of the reticuloendothelial system, which is part of the immune system, such as lymph nodes

• Mississippi- Ohio River Valley in the U.S. is the major endemic region

• Africa, Australia, India, and Malaysia are also endemic regions

• Histoplasma capsulatum is known as North American Histoplasmosis

• Histoplasma duboisii is known as African Histoplasmosis

• Presentation of Disease

– “coin” like lesions on histocytes and reticuloendothelical cells

– Pulmonary nodules are circular calcification which makes them visible on chest x-rays

– Histoplasma capulatum yeast are found in the center of the lesions

• Case Report 1

• CT scan of the cerebrum revealed a great dilatation of the cerbral ventricles due to the obstruction of the sylvian aqueduct.

• CT scan of abdominal organs revealed ascities and retroperitoneal lymphadenopathies.

• CSF showed decreased glucose and elevated protein values.

• After two weeks after admission, pt. receive antifungal drugs starting with amphotericin and fluconazole.

• Pt. expires eight day later.

• Autopsy reveals edema and areas of bronchopneumonic consolidations in both lungs; enlarged hilar nodes, which constricted the main bronchus; the abdominal lymph nodes were also swollen; there was also hepatosplenomegaly; signs of leptomeningitis and many small areas of inflammation in the brain parenchyma. • Case Report 2

• May 2007:

• Upon examination, cervical lymphadenopathy and hepatomegaly was noted. The lesion mimic cancer.

• Elective surgery was performed.

• Histopathological examination of the resected segment of the sigmoid colon revealed small oval, narrow-based budding yeast. Suggestive of H. capsulatum.

• June 2007:

• Patient was treated with I.V. amphotericin

• Significance: Histoplasmosis has been reported both in immunocompetent as well as immunocomporomised patients with dissemenated forms being more common in the latter group.

• In HIV positive patients the prevalence of histoplasmosis varies from 5% - 32% depending on the endemicity of the disease.

• There was no prior clinical suspicion of HIV infection in patient.

• There was involvement of only the sigmoid colon and there was no associated hepatosplenomegaly, lymphadenopathy, or orophyaryngeal ulcer.

• H. capsulatum may present as carcinoma. Good differential diagnosis and hx may help to avoid making the same mistake.

• Case Report 3

Sobrinho FP., Negra MD., Queiroz W., et al. “Histoplasmosis of the Larynx.” Rev Bras Otorrinolaringol. 2007; 73(6): 857-61. Article acquired on June17, 2008 from Pub Med.

• Pt. presented hoarseness, progressive dysphagia, and weight loss.

• Pt. has hx of HIV since 1996.

• Laryngoscopy showed white necrotic lesion spread throughout his larynx, edema and exophytic lesion in the upper right border of the epiglottis.

• There was no lesion on the skin.

• Occurrence is high in immunosuppressed and elderly patients, and more commonly in men. • Fever, weight loss, asthenia, liver and spleen enlargement and oral mucosa lesions are very common.

• Infection can spread to other organs such as bone marrow, lymph nodes, adrenal glands, G.I. tract, tongue and oral mucosa.

• Acute pulmonary histoplasmosis usually occurs in children below one year of age or in severe immunosuppresessed patients.

• Weight loss, fever, liver and spleen enlargement , shock, respiratory failure and disseminated intra-vascular coagulation (DIVC) are common.

• Histopathology

• Infection is acquired through the inhalation of histoplasma capsulatum microcondia, which is the spores of this fungi

• Lungs, bones, and skin are the most frequent affected site from this fungus

• It may coexist with other mycoses or even diseases, such as emphysema and tuberculosis

• Causative Organism:

– Histoplasma capsulatum

• Clinical Manifestations

• 95% of cases of histoplasmosis are unapparent or benign

• 5% have chronic progressive lung disease, chronic cutaneous or systemic disease, or fatal systemic disease

• The disease may mimic tuberculosis

Symptoms:

• Lymph nodes- inflamed lymph nodes

• Adrenal Glands- enlargement

• Central Nervous System- chronic meningitis

• GI tract- oral ulcers, small bowel micro and macro ulcers

• Eyes- inflamed inner eye

• Skin- papular to nodular rash

• Genitourinary tract- bladder ulcer, penile ulcers • Laboratory Aspects

Virulence Factors:

• In most cases, inhalation of microconidia, which in turn germinates into yeasts within the lung is the cause of virulence

Diagnosis:

• Skin scrapings examined using 10% KOH

• Body fluids, such as blood, should be centrifuged and examined

• Tissues should be stained using a Gram stain and examined

• Epidemiology and Ecology

• Ecology

- found in moderate climates, humidity, and soil characteristics

- bird and bat excrement enhances the growth of the organism in soil by accelerating sporulation

• Epidemiology

- Infects mostly immunosuppressed individuals, children less than 2 years old, and elderly people use of broad spectrum antibiotics

- air currents carry spores which exposes individuals who breath in the contaminated air

• Treatment and Prevention

Treatment

• Long-term therapy with antifungal agents at increasing doses until resolution of symptoms, such as amphotericin B, fluconazole, and intraconazole

• Surgical procedures to remove the ulcer may also be done

Prevention

• No direct away to avoid this fungal infection because it is airborne

• Avoid areas with accumulations of bird or bat droppings.

• Before starting an activity having a risk for exposure to H. capsulatum, consult the NCID Document Histoplasmosis: Protecting Workers at Risk • References

• “Histoplasmosis.” http://www.mycology.adelaide.edu.au/Mycoses/

Dimorphic_systemic/Histoplasmosis/index Article acquired on June

16, 2008 from Mycology Online.

• Histoplasmosis.” http://www.doctorfungus

Org/mycoses/human/histo/histoplasmosis_index.htm Article acquired on June 16, 2008 from Doctor Fungus.

• “Histoplasmosis Due to Histoplasma Capsulatum.” http://www.doctorfungus

Org/mycoses/human/histo/histoplasmosis_c.htm Article acquired on

June 16, 2008 from Doctor Fungus.

• Histoplasmosis Due to Histoplasma Duboisii.” http://www.doctorfungus

Org/mycoses/human/histo/histoplasmosis_d.htm Article acquired on

June 16, 2008 from Doctor Fungus.

• Sehgal S., Chawla R., Loomba PS, Mishra B. “Gastrointestinal Histoplasmosis Presenting As Colonic Pseudo-tumour.”

Indian Journal of Medical Microbiology. 2008; 26(2) 187-189. Article acquired on June17, 2008 from Pub Med.

• Severo LC., Zardo IB., Roesch W., and Hartmann AA. “Acute Disseminated

Histoplasmosis In Infancy in Brazil: Report of a case and Review.”

Rev Iberoam Micol. 1998; 15:48-50. Article acquired on June17, 2008 from Pub Med.

• Sobrinho FP., Negra MD., Queiroz W., et al. “Histoplasmosis of the Larynx.”

Rev Bras Otorrinolaringol. 2007; 73(6): 857-61. Article acquired on June17, 2008 from Pub Med.