Histoplasma antibody

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1) What is Histoplasmosis?

Histoplasmosis is a systemic disease caused by the fungus Histoplasma capsulatum . Human histoplasmosis occurs due to two varieties of the pathogen, Histoplasma capsulatum var. capsulatum and Histoplasma capsulatum var. duboisii.H. capsulatum var. capsulatum is the main causative agent of classical histoplasmosis.

2) How is Histoplasmosis transmitted?

Infection with H. capsulatum usually occurs due to the inhalation of microconidia by the host, which deposit in alveoli and rapidly convert to a parasitic yeast form in tissues. This germination and conversion may occur prior to or after ingestion by pulmonary macrophages. Conidia and yeasts are then ingested by macrophages and reticuloendothelial cells where the organism may survive within the  phagolysosomes Once inside the macrophage, the yeast multiply and travel to hilar and mediastinal lymph nodes where they enter the blood circulation for dissemination to various organs

2) What are the clinical manifestations of Histoplasmosis?

Symptomatic pulmonary histoplasmosis is most often sub-acute, which results from low-inoculum infection, presenting with a mild flu-like illness characterized by a dry cough, fever and fatigue that occurs several weeks after exposure, and the radiographs usually demonstrate enlarged hilar or mediastinal lymphnodes and patchy infiltrates, but may also be normal. 

4) What are the Histoplasmosis antibodies?

In histoplasmosis, serologic diagnosis depends on the identification of anti-H and anti-M antibodies. These antibodies are detected using histoplasmin (HMIN). HMIN is the antigenic extract which is obtained from H. capsulatum mycelial culture. The main components of HMIN to which antibody responses are detected include, the C, M, and H antigens. The C antigen is a carbohydrate (galactomannan) which is largely responsible for the cross-reactions observed with other fungal species. The M antigen is found to be a catalase and the H antigen is a β-glucosidase. As they are highly specificity to H. capsulatum, antibodies against the M and H antigen are more useful in the diagnosis 

6) What is the Immunodiffusion Test?

The immunodiffusion (ID) test qualitatively measures the precipitating antibodies (H and M precipitin lines or bands). Because of its simplicity, reliability, and potential cost effectiveness, ID testing has become significantly popular among many laboratories. ID is highly specific for the detection of anti-M and anti-H antibodies but has low sensitivity, principally in acute manifestation of the disease. In general, ID is useful for detecting antibodies 4–6 weeks after infection. While the ID test is more specific for histoplasmosis (i.e., a person who is not infected with H. capsulatum is not likely to have a positive test result) than the complement-fixation test, it is less sensitive (i.e., a person who is acutely infected may have a negative test result) . The H band appears after the M band and can be found in serum from patients during acute and/or progressive disease. The H precipitin is rarely detected after HMIN skin testing. The M band is detected more frequently than the H precipitin and it appears soon after infection and may indicate a prior infection, acute disease or a chronic progressive disease. The M precipitin reaction can persist for up to 3 years after the resolution of the disease and can also be stimulated following the skin testing with histoplasmin in people who have never had any contact with H. capsulatum or infection. The presence of both the H and M precipitins is considered to be conclusive for the detection of histoplasmosis, however the status of disease requires clinical assessment of the patient.

7) What is the Complement Fixation test?

Another common assay for the detection of antibody in histoplasmosis is the complement-fixation (CF) test. This procedure measures presence of antibodies to either the intact yeast form or mycelial (HMIN) antigen. CF is more sensitive than the immunodiffusion test but it has less specificity. It is notable that inter-laboratory variation in the antibody titers detected may be influenced by the strain of H. capsulatum that is used for antigen preparation. A disadvantage of H. capsulatum CF assay is that it may also detect cross-reactive antibodies in sera from patients with other mycosis such as blastomycosis, candidiasis, coccidioidomycosis and paracoccidioidomycosis. Another drawback of CF is that negative results may occur in culture-proven fungal disease, because of the blocking effect of rheumatoid factor and cold agglutinins that may develop during histoplasmosis. Complement-fixing antibodies may be seen in 3 to 6 weeks (sometimes as early as 2 weeks) following infection by H. capsulatum in 95% of the patients with histoplasmosis, and repeated tests may give positive results for months. According to literature Titers between 1:8 and 1:16 are considered weakly positive and are observed in almost one quarter of patients. However, these titers may be indicative of past infection and may also be detected in the serum of healthy persons from regions where histoplasmosis is endemic. A high titer (1:32 or greater) or a fourfold increase in titer over time may indicate active histoplasmosis. Antibody titers will gradually decline and eventually disappear within months to years following recovery in the absence of re-exposure, but persist for years in individuals with recurrent exposures.

8) What are the other antibody tests for Histoplasmosis?

Latex agglutination tests, Western blot and ELISA

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