Histoplasmosis: Introduction – Endemic Mycoses

00:01 Endemic mycoses are diseases caused by fungi that exist in very specific geographical locations, that's why we call them endemic, because the fungi are endemic to certain geographical regions. And the first one I'd like to discuss is histoplasmosis, which is a disease caused by the fungus, Histoplasma capsulatum and a photograph of the organism is shown here.

00:29 This is a section of tissues containing the yeast form of the organism. And the two organisms we are going to talk about today are dimorphic fungi. They exist filamentous form in the environment, and they transform to the yeast form when they get into a host. Histoplasma is located throughout the central and eastern states of the US; you can find it in parts of Central and South America, parts of Africa, Asia and Australia. It is really geographically limited; you can see there are many parts of the world where it does not occur.

01:04 The fungus lives in the soil and it particularly likes soil with high nitrogen content and the best way to get high nitrogen, besides adding fertilizer to soil, is to have bird droppings or bat droppings in the soil, because bird and bat excrement has high levels of nitrogen in it. So histoplasma is typically associated with places where we find bird and bat droppings, like caves, where the bats would be, or wherever we keep birds, roosts and coops of various sorts, even old buildings, where pigeons are roosting, you know old building, their ledges are often covered with pigeon excrement, that's a source of this fungus.

01:55 There are also clusters of infections in people who like to explore caves, this is called spelunking. When old buildings are demolished, infections are often associated with that.

02:08 Or any construction work where you're digging soil and again the workers are in the area, they're inhaling the spores, you get outbreaks of histoplasmosis. The largest outbreak that has been documented, a hundred thousand infected individuals, not just the people working here, but people walking in the area, was after the demolition of an amusement park in Indianapolis in the US. So this was a site that has been around for a long period of time, it had soil associated with it and probably lots of bat droppings, sorry lots of bird droppings, hopefully no bats and when they demolished it, it created an aerosol of the spores and these were inhaled and caused the disease. So now you can tell already how histoplasmosis is acquired, you inhale the spores from the environmental mold form. In the environment the fungus grows in mycelial form and it's producing spores in order to reproduce, and the spores by nature are very light and they travel in the air. So if you disturb the soil, they readily come up and you inhale them and they can cause this disease. You inhale the spores into your lungs and there, when it begins to grow, it transforms into the yeast phase. If these spores were in the environment in the soil, they would grow as mycelia. But in your lungs, the chemical cues they get there make them grow in yeast phase, which of course are single cells and they divide by budding.

03:39 Macrophages are one of the main defenses against histoplasmosis, but these organisms can be taken up by the macrophages, which are phagocytic defense cells in our body of course and they can remain viable inside of the cell for long periods of time, so eventually they will be cleared in healthy people, but this prolongs the infection. Cellular immunity is important for defense against this fungus and primarily CD4 positive, T helper lymphocytes and macrophages are essential for defense against histoplasma. We don't seem to have any role for antibodies in the response. Antibodies are produced and we use those for diagnosis, but they don't seem to be protective. So phagocytic cells like macrophages, the involvement of CD4, T helper cells suggests that cytokine production is important. So killing by macrophages eventually occurs but it takes several weeks. In the meantime the organism is spreading in the lung and it may get out of the lung as well and spread systemically depending on the host.

04:45 As soon as cell-mediated immunity is established and effective, again, which takes weeks, infection is curtailed and cleared. You are immune throughout your whole life after an infection, so typically you don't get another exogenous infection. But within you the yeast cells can remain in what is called a granuloma. So granuloma are simply foci where the yeast have multiplied and they are now surrounded by tissue, so the yeast don't spread anymore. And they're dormant, they don't divide in a granuloma. And normally that would not present a problem, you don't even know that you have such granulomas, but if you are ever immunosuppressed, these yeast may start to grow again, because they are kept in check by the immune system and then that can cause problems. So why would you suddenly be immunosuppressed, well if you had an infection with a virus that was immunosuppressive like HIV or measles virus, or if you needed an organ transplant and you need to take drugs to prevent rejection of the organ. There are many reasons why this would happen. And in our medically oriented society, we are doing more and more immunosuppression for medical procedures, so these kinds of infections increase.

06:01 The extent of your initial infection and what kind of disease you get depends on how many spores you inhale and your cell mediated response. So you can imagine if you're working in a construction site and you're inhaling large amounts of spores because the soil is disrupted, you could have more serious disease as a consequence. But if you just inhale a few, your macrophages will take care of them and you won’t even notice that you're sick. In fact most people inhale spores regularly, but have no clinical disease, or if any disease is apparent, it's a mild pulmonary infection, may be a flu-like illness, where you have some respiratory involvement and some fever. You would not even know it's histoplasmosis. The physician, if you went to see a physician, they say “Oh, it's a flu-like illness”, and that would be the end of it. It would eventually clear and you wouldn't know that you had histoplasmosis.

06:56 Some individuals who inhale sufficient numbers of spores will develop pneumonitis or pneumonia, this can happen even in a healthy host, again it depends on how many spores are inhaled and your immune status to a certain extent, and I also think that a lot of people who are apparently healthy do have subtle immune system defects that we don't know about, which could contribute to the development of clinical symptoms.

07:20 People with lung diseases, like chronic obstructive pulmonary disease are at risk for serious histoplasmosis. They can develop what's called chronic cavitary pulmonary histoplasmosis, this is a fatal progressive infection. So if you had any lung diseases, such as this one, or if you smoke, you should really avoid areas where histoplasma is known to lurk. If you are again, immunosuppressed, if you have AIDs, you have an organ transplant and are receiving immunosuppressive drugs you're more likely to get symptomatic systemic disease.

08:00 Remember the infection is constrained to the lung in healthy people depending on the inoculum, but if you have immunosuppressive state, the disease is more likely to be more serious and can spread elsewhere.