Multistate Epidemiology of Histoplasmosis, United States, 2011–20141

Increased awareness could lead to appropriate diagnosis, prompt treatment, and better patient outcomes.

by Histoplasma capsulatum. Infection may be asymptomatic or take one of four clinical forms: • Acute benign respiratory -mild respiratory illness with general malaise, fever, chills, headache, myalgia, chest pains, nonproductive cough and scattered small calcifications of the lung.
• Acute disseminated -debilitating fever, GI symptoms, bone marrow suppression, lymphadenopathy. Most frequent in children and immunosuppressed; fatal if not treated.
• Chronic pulmonary -clinically and radiologically resembles chronic pulmonary tuberculosis with cavitations, usually in middle-aged and elderly persons with underlying emphysema. A systemic mycosis of varying severity, with the primary lesion usually in the lungs.
Clinical manifestation ranges from asymptomatic to minor self-limited or life-threatening illnesses. Four clinical forms are recognized: • Acute respiratory: Varies from a mild respiratory illness to temporary incapacity with general malaise, fever, chills, headache, myalgia, chest pains and nonproductive cough; occasional erythema multiforme and erythema nodosum. Multiple, small scattered calcifications in the lung, hilar lymph nodes, spleen and liver may be late findings.
• Acute disseminated: with debilitating fever, GI symptoms, evidence of bone marrow suppression, hepatosplenomegaly, and lymphadenopathy. A rapid course, most frequent in infants and young children and immunocompromised patients. Without treatment, usually fatal.
• Chronic disseminated: with low-grade intermittent fever, weight loss, weakness, hepatosplenomegaly, mild hematological abnormalities and focal manifestations of disease.
• Chronic pulmonary form: Clinically and radiologically resembles chronic pulmonary tuberculosis with cavitation. Most often in middle-aged and elderly men with underlying in laboratory criteria). A case is also considered probable with clinically compatible symptoms, no laboratory confirmation, and an epi link to a suspected source during an outbreak.
• Confirmed: A patient that is clinically compatible, and culture positive for H. capsulatum or has a 4-fold rise in titers collected 2-4 weeks apart (numbers 1 or 2 in laboratory criteria).

Acute Disseminated Histoplasmosis
• Probable: A case that has fever and weight loss with or without respiratory symptoms, and evidence of H. capsulatum by either histopathology staining or DNA probe of a specimen from an extrapulmonary site*.
• Confirmed: A case that has fever and weight loss with or without respiratory symptoms, and a positive culture from an extrapulmonary site*.

Indiana
Clinical disease • Asymptomatic -individual has no clinical signs or symptoms, but has immunological evidence of infection. This is a common clinical disease presentation in Indiana and is not reportable as histoplasmosis.
• Acute disseminated -is an illness of short duration that involves other organs in addition to the lungs. It is marked by cough, exhaustion and enlargement of the liver and spleen.
Symptom severity is dependent on magnitude of exposure to fungal conidia.
• Chronic disseminated -a prolonged illness involving organs other than the lungs. It may include by fever, anemia, hepatitis, pneumonia, endocarditis, meningitis, and ulcers of the mouth, tongue, nose, and larynx.
• Chronic pulmonary -resembles tuberculosis Laboratory test used in confirming case • Culture -a positive culture for Histoplasma capsulatum is sufficient for case confirmation.

CLINICAL DESCRIPTION:
A systemic fungal infection of varying severity caused by Histoplasma capsulatum.
Infection may be asymptomatic or take one of four clinical forms: • Acute benign respiratory -mild respiratory illness with general malaise, fever, chills, headache, myalgia, chest pains, nonproductive cough and scattered small calcifications of the lung.
• Acute disseminated -debilitating fever, GI symptoms, bone marrow suppression, lymphadenopathy. Most frequent in children and immunosuppressed; fatal if not treated.
• Chronic pulmonary -clinically and radiologically resembles chronic pulmonary tuberculosis with cavitations, usually in middle-aged and elderly persons with underlying emphysema • Chronic disseminated -low-grade fever, weight loss, weakness, liver and spleen enlargement, mucosal ulcers, subacute course with slow progression; fatal if not treated.
LABORATORY CRITERIA FOR CONFIRMATION: • Isolation of H. capsulatum from culture of bone marrow, sputum, or lesions, OR • Histological demonstration of intracellular yeast cells from bone marrow or tissue biopsy, OR • Detection of H. capsulatum polysaccharide antigen in urine or serum, OR • Rise in CF titers to either histoplasmin or yeast-phase antigen.

COMMENT:
Positive histoplasmin skin test IS NOT sufficient evidence.
REPORTING CRITERIA: Signs/symptoms and/or laboratory confirmation Page 7 of 12

Michigan
In order for a patient to be considered to have an acute case of histoplasmosis, they must have a clinically compatible illness coupled with laboratory evidence of infection. Please use the following case definition when classifying cases for MDSS entry:

Clinical Description
A case of acute histoplasmosis is defined as an influenza-like illness with two or more of the following symptoms: fever/chills, cough, chest pain, weakness, or myalgia/arthralgia.

Laboratory Criteria for Diagnosis
Probable: • Complement fixation titer to the yeast-phase antigen ≥1:32 or A confirmed case is defined as a Minnesota Resident with at least one of the following: • positive Immune diffusion (ID) test with an H band, • positive ID test with an M band, • 4-fold or greater rise in titer on Complement fixation (CF), • single CF titer of ≥1:32 (can be yeast Ab and/or mycelial Ab),