Histoplasma capsulatum, cause of histoplasmosis in humans and other animals, Tom Volk's Fungus of the Month for January 2000

Tom Volk's Fungus of the Month for January 2000

This month's fungus is Histoplasma capsulatum, cause of histoplasmosis in humans and other animals.

Histoplasma capsulatum macroconidia and microconidia

This month's fungus is a dimorphic pathogen that causes a disease called histoplasmosis, also known as Darling's disease, reticuloendotheliosis, reticuloendothelial cytomycosis, Ohio Valley disease, tingo, and Maria fever. It is actually a very common disease in the Ohio and lower Mississippi River Valleys, but rarely causes severe disease.

Histoplasma capsulatum is called a thermal dimorph because it has two forms. In nature at "room temperature" about 25° C it takes on a mycelial (filamentous) form, forming the macroconidia to the left. as well as smaller microconidia. At body temperature (37° C) it morphs into a yeast, shown to the right. The two forms are shown below, grown in separate test tubes at different temperatures. In culture below 35° it and on natural substrates it grows as a white to brownish mycelial fungus, with characteristic echinulate oval or pyriform macroconidia (8-16 um diameter) and microconidia (2-5 um diameter). When inhaled into the alveolar spaces it is primarily the microconidia that germinate and then transform into small budding yeasts 2-5 um diameter. Yeast cells are found in reticuloendothelial system. The fungus also grows as a yeast in culture at 37° C.

Histoplasma capsulatum yeast and mycelial cultures at different temperatures

The true human-pathogenic fungi have a yeast phase inside the human body to get around the human immune system-- although the conidia formed by the mycelial form are the cause of infection. Not only does the phase shift, but there is a concomitant change in the chemicals making up the wall of the fungus. Thus the antigens change and the immune system must retool, giving the fungus just enough time to establish itself in the lungs. The other true human pathogens include:

Blastomyces dermatitidis, cause of a lung disease called blastomycosis, Chicago disease, Namekagon River fever. This disease is endemic to the Central, Southern and Northern United States and Canada, as well as many other areas.
Paracoccidioides brasiliensis, cause of the lung disease paracoccidioidomycosis (the longest word I make my medical mycology student learn to spell!), mostly restricted to South America.

The other true human-pathogenic fungus is Coccidioides immitis, cause of coccidioidomycosis, also known as Valley fever. It is restricted mostly to the desert southwest USA and the San Joachin Valley in California. It is probably the most virulent of the human pathogenic fungi. It is dimorphic, producing a mycelial form in nature and a spherule form in the host organism.

In addition three are two other opportunistic pathogens that are dimorphic. Sporothrix schenckii causes "rose picker's disease," and must be traumatically implanted under the skin to cause infection. The other is Penicillium marneffei, which is an opportunistic fungal pathogen so far found only in southeast Asia.

Histoplasma capsulatum calcification in spleen

Histoplasma capsulatum yeast budding in tissue

Infection results after inhalation of the conidia. This results in a variety of clinical manifestations. Approximately 95% of cases are inapparent, subclinical, or completely benign. The disease is diagnosed only by the X-ray findings of residual areas of pulmonary calcification and a positive histoplasmin skin test. Approximately 40 million people in the USA (that number is not a typo) have had the disease, and 200,000 new infections occur every year

The remaining 5% develop a chronic progressive lung disease, a chronic cutaneous or systemic disease, or an acute fulminating rapidly fatal systemic infection. The latter form is particularly common in children. Following infection there is an acute alveolitis, and macrophages engulf the organism, resulting in an inflammatory reaction. Macrophages probably carry the organism to other parts of the body very early in the course of the infection.

There is a skin test for histoplasmosis that was developed in 1941 by Van Perris. The fungus grown in broth and filtered. The filtrate is inoculated under skin-a red area at least 5 mm after 48 hours is considered a positive test.

According to skin tests, the largest area with high prevalence is the middle section of the North American continent-- E.g in a series of tests in Kansas City, by age 20, 80-90% of population had a positive histoplasmin skin test. There have been similar results in other areas. So the histoplasmin skin test merely indicates that one has lived in the central USA for a time, and has no diagnostic value.

In 1997 it was reported in the press that Bob Dylan (yes that Bob Dylan) was suffering from Histoplasmosis, but his was a very unusual form, infecting the lining of his heart. This usually signifies some underlying health problems, but since I am not a medical doctor I will not speculate. So where did Bob Dylan pick up histoplasmosis? This is an Audio Daily Double. Click here and pick your choice for an answer.

Histoplasma capsulatum sign in a starling area

The fungus also forms a sexual state, forming spores by meiosis. It is a heterothallic ascomycete. The teleomorph or sexual state is Ajellomyces capsulatus found in the Arthrodermataceae, Onygenales, Ascomycota. It forms a gymnothecium, which is similar to the cleistothecium formed by powdery mildews, but the structure of a gymnothecium is much more open, allowing the spores to fall out and be dispersed. The fungus has been found all over the world. Its growth is particularly associated with the guano and debris of birds and bats, particularly with birds that congregate in large numbers, such as starlings. The picture to the left is in a particularly bad area in Kentucky, where the guano or feces of the starlings was five to six inches thick in places with Histoplasma capsulatum essentially in pure culture. If you look closely you can even see a starling perched atop the sign. As you may know, starling are European birds that were imported into New York City in 1890 by Shakespeare aficionados who wanted to have all the birds that were mentioned in Shakespeare's plays and poems. The dirty starling has since spread throughout the east and has replaced many native species.

Before histoplasmosis came to be widely recognized (before the early 1950's), its disease symptoms were mistaken for tuberculosis . Of course that meant sufferers of the disease were given antibacterial antibiotics to treat the disease. This usually worsened the disease because after the bacteria were killed off there was essentially no competition for the fungus in the body and it could take over. A proper diagnosis is very important. So how much medical mycology study do you think the average doctor gets in medical school? Sometimes only one or two lectures!!! That certainly is not enough, especially with fungal diseases becoming so important because of people's compromised immune systems.

However, please do not write to me about any of your medical problems caused by fungi. I am not a medical doctor. Someday I'll write about the mysterious unsolicited package I received in the mail from someone who read my web page in southern California. I'm still really fuming about that one.

Here are some very good links to learn more about Histoplasmosis

Ocular Histoplasmosis, a.k. Presumed Ocular Histoplasmosis Syndrome, or POHS. Also has many links to other Histoplasmosis sites.
Histoplasmosis Reference Laboratory, Indianapolis, Indiana. They have a Histoplasmosis Information Guide, a Histoplasmosis Antigen Test and an Itraconazole Bioassay, as well as a wealth of other information available as both html and power point presentations.

Many thanks to Dr. John Rippon, Dr. Al Rogers, and Dr. Tex Beneke for providing this month's pictures. I believe they're all in Paris as I write this, celebrating the year 2000. Happy New Year to them and to you.

If you have anything to add, or if you have corrections or comments, please write to me at volk.thom@uwlax.edu

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