Coccidiomycosis (Valley Fever) – Endemic Mycoses

00:01 Alright let's move on to the second endemic mycoses that we're going to talk about. This is coccidiomycosis. This is caused by the fungus coccidioides immitis. The disease is also known as a Valley fever and this is also a dimorphic fungus and this is a beautiful image taken from a tissue section, showing the growth of the fungus in a tissue of a patient and in particular you can see these sacks full of tiny spores, they are called endospores. And this is one of the stages of infection by this organism. Once the spore gets in you, it can multiply and then the fungus can produce additional spores in these sacks and these can move around the body. Coccidiomycosis or valley fever is associated with a very specific part of the United States, in particular what's called the Sonoran life zone and some of you may recognize that this is mainly the southwestern part of the United States. The organism is only found in this region, in this so-called Sonoran life zone, which comprises Arizona, Southern and interior California and parts of New Mexico and Texas.

01:14 The organism isn't found anywhere else, at least so far we haven't seen it anywhere else and this is where this disease would be evident. So this is a really good example of an endemic disease which is geographically restricted. The organism grows in the environment and one place where it has been shown to really be prevalent is in the burrows of desert animals.

01:36 These areas of the country are quite dry, they're desert like in their ecology and in the burrows of animals this fungus seems to persist and this of course burrows are dark and somewhat moist compared to the surface, which is very hot and dry. So the Sonoran life zone comprises this area of the US, the semiarid environment fosters the growth of the organism in these animal burrows. Now we know that when it rains, followed by a warm period, there are typically blooms in these organisms. So you can imagine the rain supplies something that the coccidio needs to multiply and then with the emerging sun, the organisms multiply and these conditions, rainfall, followed by sunlight, are associated with outbreaks of the disease in this Sonoran life zone.

02:29 This is a chart showing you the number of cases from 1998 to 2013 of coccidioidomycosis, and of course this is in the Sonoran region in Arizona California and its neighboring states Nevada, New Mexico and Utah. You can see that the number of diagnosed cases were below 5000 in 1998 and peaked at over 20,000 in 2011. They have since gone down somewhat and we don't quite know the reason for this, it may have something to do with the weather at the time. But there are over 20,000 diagnosed cases in that year in this area, so this is a substantial disease burden. In fact serological surveys have shown that up to 80% of the population in this Sonoran life zone has evidence of prior infections. So a lot of people are infected, not all of them of course become ill and this is consistent with a lot of the pattern of fungal infections that we've talked about so far. Many people inhale spores on a daily basis, but not everyone gets sick and if you do a population survey, you can see evidence of infection. So the way you acquire this infection should be immediately familiar, you inhale spores, they enter your lungs and go down into your alveoli, the very terminal sacks in the lung and there, they transform into large spherules that are filled with endospores and those are the spherules that I've showed you in the initial photograph. These are filled with spores and the key issue with these is that they resist phagocytosis.

04:02 As you may guess, macrophages and phagocytic cells in general are important for clearing yeast infections and these structures are so large that they can't be taken up by these cells, so it's sort of an evolved strategy for avoiding immune clearance. From the lung, these spores can spread to other organs and disseminate the infection depending on the individual.

04:23 Now we understand that the host response that's important for limiting this infection in a healthy individual is a mixture of neutrophils, T lymphocytes and macrophages. Cell-mediated immunity is important to eradicate the infection and in AIDS patients where cell-mediated immunity, as well as many other types of immunity is defective, as a consequence of viral infection, disseminated infections are frequent. So again, the theme in this infection, these spores get in the lungs, they're typically restricted there and can cause a lung disease but don't spread, but if you have defective immunity the spores will move out and spread to other tissues. Again these yeast, these fungi can cause foci or granulomas in different parts of the body that remain dormant and you can recover from the infection, you won’t even know that you have a granuloma, but again, if you're immunosuppressed many years later they can reactivate, the yeast can start to multiply and you can have disease again.

05:21 So most people who inhale spores say they have no symptoms at all, that 80% seropositive number reflects that, or maybe a mild flu-like illness very similar to histoplasmosis, you wouldn't even know that you had a fungal disease. Acute pulmonary infection, if it's going to happen, happens a few weeks later, it takes a while for the organisms to multiply and this can be a flu-like lung illness often called desert rheumatism or valley fever, and associated with it, you may have nodules on the skin caused by yeast spreading there and multiplying. You can have disseminated coccidioidomycosis in pregnant women or immunosuppressed individuals, in other words, the organisms move from the lung to the surrounding tissues as a consequence of reduced immune surveillance. Pregnant women typically have reduced immunity as a consequence of the pregnancy, immunosuppressed individuals by definition, whether it’d be AIDS or organ transplants that have lowered immunity. So that can encourage the growth of the organism outside of the lung. The organism can get into the brain and it will cause chronic meningitis, a chronic infection of the brain and again, this happens in people without a good immune system, this needs to be treated and you need to receive treatment for your entire life.

06:45 If the organism enters your brain, then you can never get rid of it, you have to take these drugs forever. If you stop taking them, you will have relapses of disease and this is a serious issue.

06:58 How do you diagnose coccidioidomycosis? You can try to grow the organism from the tissues that are involved. You can take lung samples, sputum samples for example or other body fluids, but it is a little dangerous, because it's been known that culturing this organism in the lab has actually caused outbreaks among laboratory workers. You have to be very careful while you're doing this. You can look at sections of tissues, by histopathological examination and find spherules. So spherules like these beautiful ones that you can see in this slide, you can see one breaking open and releasing the endospores in the lower left. These are very characteristic of coccidioidomycosis infection, so you can readily make this diagnosis.

07:39 You can also look for antibodies that we produce against the fungus using various techniques like ELISA.

07:46 Treatment of coccidioidomycosis is typically done with itraconazole or fluconazole. This is a long-term treatment, even for mild infections, 1 to 2 years is required. More severe infections, where the fungus has left the lung and become systemic require amphotericin B and as I said, meningitis caused by coccidia requires treatment with fluconazole, this compound shown here, and you need to do that for the rest of your life. If you stop treatment, the infection will recur and you will have symptoms of meningitis as well.

08:22 So we can look at our antifungal chart, which you may remember from our previous lecture and see which of these antifungals are used to treat these endemic mycoses, histoplasma and coccidioi infections, the polyenes, as you can see, amphotericin B, the azoles including ketoconazole are important and at the bottom of this chart, itraconazole and fluconazole are used.

08:52 Let's take a quick look at one of the other systemic fungi capable of causing mycosis, and that's Blastomyces Dermatitis.

08:59 The clinical presentation and treatment recommendation are very similar to those of cocci, but there are a few key differences that test writers do like to highlight.

09:08 First, the geographical distribution of these fungi is very clinically important.

09:13 They are endemic to different regions, and just like Cox's is endemic to the western desert climates.

09:18 Blast Doh is more commonly associated with the Midwestern and South Central states because this overlaps with Histo’s region.

09:25 Testers usually highlight the Great Lakes in the questions.

09:28 Then the next important highlight is that blast to replicates the broad based budding, which is illustrated on this image.

09:36 You should try to memorize this picture and specifically remember that Blasto is close to the size of a red blood cell while histo is smaller than red blood cell in Cocci is larger than red blood cell.

09:48 These are all high yield facts that can help you on test day.