Histoplasmosis
2017 Case Definition

Background

Histoplasmosis is one of the most common endemic mycosis in the United States and encompasses a spectrum of disease ranging from self-limited respiratory illness to disseminated infection (1-2). In the United States, histoplasmosis is caused primarily by Histoplasma capsulatum var. capsulatum and is endemic in the Ohio and Mississippi River valleys as well as other areas. Another variety of H. capsulatum (var. duboisii, sometimes referred to as H. duboisii), causes a disease known as African histoplasmosis, which has rarely been reported in the United States. Histoplasmosis is typically acquired through inhalation of spores found in soil contaminated with bird or bat droppings. No direct human-to-human transmission has been reported. Symptoms generally develop 3–14 days after exposure, although many infections are asymptomatic (3-5). Acute pulmonary histoplasmosis is the most common form of disease, and symptoms typically include fever, headache, malaise, and cough. Severe pulmonary disease can involve a wide range of complications (3). Several laboratory methods are available for diagnosis of histoplasmosis, including culture, histopathology,and antigen, antibody, and nucleic acid testing (5-6).

Clinical Criteria

Clinical presentation includes either:

At least two of the following clinical findings:

• fever,
• chest pain,
• cough,
• myalgia,
• shortness of breath,
• headache, or
• erythema nodosum/erythema multiforme rash; OR

At least one of the following clinical findings:

• Abnormal chest imaging (e.g., pulmonary infiltrates, cavitation, enlarged hilar or mediastinal lymph nodes, pleural effusion);
• Clinical evidence of disseminated disease:
  • gastrointestinal ulcerations or masses;
  • skin or mucosal lesions;
  • peripheral lymphadenopathy;
  • pancytopenia, as evidence of bone marrow involvement;
  • enlargement of the liver, spleen, or abdominal lymph nodes; or
  • meningitis, encephalitis, or focal brain lesion.

Laboratory Criteria For Diagnosis

Confirmatory laboratory criteria:

• Culture of H. capsulatum  from a clinical specimen,
• Identification of characteristic H. capsulatum  yeast in tissue or sterile body fluid by histopathology,
• ≥4-fold rise in H. capsulatum  serum complement fixation antibody titers taken at least 2 weeks apart,
• Detection in serum of H band by H. capsulatum  immunodiffusion antibody test,
• Detection in serum of M band by H. capsulatum  immunodiffusion antibody test after a documented lack of M band on a previous test (i.e., seroconversion),
• Demonstration of H. capsulatum-specific nucleic acid in a clinical specimen using a validated assay (i.e., polymerase chain reaction (PCR)).

Non-confirmatory laboratory criteria:

• Identification of characteristic H. capsulatum  yeast in tissue or sterile body fluid by cytopathology,
• Detection in serum or cerebrospinal fluid (CSF) of H. capsulatum  antibodies by single complement fixation titer of 1:32 or greater (e.g., 1:64),
• Detection in serum or cerebrospinal fluid (CSF) of M band by H. capsulatum  immunodiffusion antibody test without a previous negative test,
• Detection of H. capsulatum  antigen in serum, urine, or other body fluid by an enzyme immunoassay test.

Epidemiologic Linkage

Epidemiologically linked (e.g.: common environmental exposure) with a confirmed case.

Criteria to Distinguish a New Case from an Existing Case

Following acute histoplasmosis, complement fixation titers and M-band on immunodiffusion antibody testing typically remain elevated for several years. People with chronic histoplasmosis may have cultures yielding H. capsulatum  and positive antigen enzyme immunoassay testing for months or more. Distinct repeat infections have also been reported, typically involving acute pulmonary disease in endemic areas. To minimize duplicate counting of chronic infections and missed repeat acute infections, illnesses in a given person should be counted no more than once every 24 months.

Probable

A clinically-compatible case that meets non-confirmatory laboratory criteria*; OR
A case that meets confirmatory laboratory criteria, but no clinical information is available; OR
A clinically-compatible case that does not meet laboratory criteria, but is epidemiologically linked to a confirmed case.

*Illness in a person with compelling evidence (e.g., culture, histopathology, seroconversion) of a different fungal infection, such as blastomycosis or coccidioidomycosis, and meeting only non-confirmatory laboratory criteria for histoplasmosis should not be counted as a case of histoplasmosis since other fungal infections can cause false positive H. capsulatum  antigen and antibody test results.

Confirmed

A clinically-compatible case that meets confirmatory laboratory criteria.