Extra notes from last lec :

* Oral Candidiasis also known as oral thrush

* Candida Stomatitis is a form of Oral Candidiasis.

* Mycetoma if it is caused by Fungi it is called Eumycetoma .. as it may be caused by bacteria . So Eumycetoma is a fungal Mycetoma.

* no vaccine is available to prevent Candidiasis.

Thanks to Lyn Smadi

Microbiology sheet #4 :

Candidiasis is very common and infection is often related to the mucosa our body , especially the oral cavity .

It can also affect the skin , the intestinal mucosa and the mucosa of the genital tract , mainly among women and it produces vaginal discharges , therefore due to the wide spread of candidiasis , we use anti-fungal drugs.

But the use of these drugs is not similar to anti-bacterial drugs sometimes before using anti-fungal drugs you have to know exactly if the patient , especially adults , that they are not suffering from underlight diseases or exposed to radiation or having an oral treatment or any other suppressive drug , because you cant do anything and you cant eradicate the presence of the follicles without dealing first with the other conditions or diseases .

But if the patient is normal but have small candidiasis for one or other reason like severe dehydration , diarrhea etc . candidiasis will only be present for a short period of time in the oral cavity. in such cases, the only way to treat it is by topical ointments for 2 or 3 days , not necessarily to give a 12 course for 5 ot 7 days to 2 weeks, 2 or 3 days applying is enough.

The use of systemic anti-fungal drug might sometimes ,in cases of immune-deficiency patients, require an ORAL anti-fungal drug NOT a topical one .

Types of anti-fungal drugs divided mainly into :

1- Oral drugs : ex. Nystatin which have many varieties : Myconystatin , glovonystatin etc.. , in addition we have a group of AZOLs drugs represnented by : Miconazol, Clotrimoxazol.Griseofulvin is used mainly to treat tinea capitis and tenia pedis.

In general all anti-fungal drug don’t differ in the mechanism of action ( all of them interact with the Ergosterol in the yeast cell membrane and will produce a complex and this complex will disrupt the fungal cell membrane )They differ in pharmacokinetics in the distribution of the drug the internal body organs , excretion of the drug and so on … but NOT in the mechanism of action in relation to fungal cell membrane .

2- Systemic drugs : it’s not part of our job to deal with such type of infection , these patients should return to internal medicine experts.But generally if there is a wide spread of fungal infection in the lungs , blood , CSF “ cerebro-spinal-fluid”, the meninges etc.. often the only way to treat the patient is using systemic anti-fungal drugs.Ex : fluconazole : which can be used also as a topical drug.And Amphotercin B.These drugs should be given under strict indications there should be a proof that there is a systemic fungal infection.(why ?) because these drugs are often associated with side-effects , mainly damage the liver , kidney , WBCs etc…Should not be used by dentist not to cause any side effects, but topical ointments are usually used by dentists.

Concerning the identification of candida :

This picture will indicate the presence of a type of candida especially candida albicans because it’s the ONLY candida species that produce pseudo-hyphae in vitro , in vivo it may produce pseudo-hyphae but you cant recognize it, in addition you will see at the ending of these elongated cells “part of pseudo-hyphae” there will be larger spores called chlamydo-spores .It’s called chlamedo-spores because it has a double cell wall and can be recognized in wet preparation, they are found at the tip of the end.Spores that is between two separate nearby cells the usually rounded or oval called blastospores. Remember they are associated with candida albicans.

In this picture it’s very important to know that an old type of yeast to some extent considered related to gram +ve bacteria , called 2-gram +ve. it can give an impression of gram –VE , but in candida it’s more recognized as gram +ve.

Concerning culture :Candida can be easily grown on many culture medias , but we usually use Sabouraud dextrose agar after a Belgium scientist.Colonies of candida whitish to grey and larger than bacteria , more mucoid , rapid growing ,

generation time is 12hrs so within 24hrs to 48 hrs u can recognize it , it grows in different room temperatures .

15 yrs ago they have developed a type of culture media called Chrom-Candida Agar special type of medium convey specific type of dyes , so according to the fermentation of glucose in this medium, we can recognize the presence of different species .At least we have 5 common species which we encounter in association with infection of candidiasis in oral cavity or vaginal etc ..And by the use of chrom-candida agar , you can easily detect these common species without using sugar utilizing tests which require 3 or 4 days , by chrom agar after 48 hrs you can detect the species of candida :Candida albicans is green .Candida tropicalis is blue.Candida glabrata is rose and mucoid in form.Candida krusei is also rose but rough colonies.These 5 species can be easily isolated and recognized by Chromo agar .==> very rapid way.

Some species are colorless in this situation we have to do biochemical tests.So why is it important to differentiate between candida species even if they produce the same clinical features “ signs and symptoms , whether in the oral cavity or the vaginal mucosa ?Two reasons: 1- We have recognized in the last 10 yrs the developing of anti-fungal

resistance , especially among two species : candida glabrata and candida krusei and this means if we give a patient an empirical treatment “

=without knowing the exact candida species” using anti-fungal drug you will notice after 24hrs that the patient is still suffering from candidiasis and hasn’t recovered .In this case you have to think that the patient is infected with a kind of candida which is resistant to this anti-fungal drug.Mostly is due to candida glabrata or krusei.That’s why when you see the recurrence of candidiasis in a patient you have to take a swap from the tongue or gingiva etc …, send it to the lab to detect the type.It’s not necessary to do an anti-microbial susceptibility test like in bacteria because it’s costly, about 10 JDs ,so knowing the species help.

So in the case of skin , oral cavity, vaginal mucosa “mild infection” candidiasis doesn’t need an anti-fungal susceptibility test.But in the case of blood or meninges , we have to do culture media and anti-fungal susceptibility test to know the specific type of anti-fungal drug to use or you will expose your patient to side-effects, so there is no trial of a certain drug , you have to be sure .

Before 10 yrs there was no problem in treating candidiasis.In bacteriology we took staphylococcus aureus associated with 30% of infections in hospitalized patients, 70% are resistant to all type of penicillin and cephalosporin drugs, so we have to use a more toxic and more expensive drug ex. Vancomycin , clindamycin they use it in dentistry a lot but if staph is resistant to methicillin and oxacillin it cannot help sometimes side effect is bloody diarrhea in relation to pseudo-membranous colitis so following the treatment in the first week , if he has developed blood in his stool means he developed pseudo- membranous colitis and necrosis in the large intestine and damage in the blood vessels in itchildren may die if they developed it, but the reason is not pseudo-membranous colitis , it’s the toxin clostridium difficile.

2- Epidemiology : the change in the species of candida in the community, in types of krusei and glabrata species.

Now we will talk about Opportunistic Systemic Mycoses:

We don’t live in a sterilized condition, we are always exposed to large number of bacteria and fungal spores, carried by dust and in association with food.

In case of fungal pathogens , we have few species but very common, easily can be recovered from the surface of a table or clothes or in our homes , one of these groups is : aspergillus

We have many species of aspergillus :

A.niger black

A. fumigatus blue to green

A. flavus yellow , associated with the production of very dangerous toxin called aflatoxins .

Another common fungal pathogen is Mucor and related to this fungi is Rhizopus.

Also a fungal pathogen is Alternaria it’s a vegetative fungus , associated with all types of vegetation including fruits , tomatoes….

in this picture we see large number of spores of the aspergillus , they are carried on vesicles , not on the head of the vesicles, arranged in a smaller filaments, in very beautiful arrangement.

We identify aspergillus as a filamentous fungi in relation to hyphae , if it’septated or not septated ,

in number of branching , vesicles , arrangement of head, the structure of head, the type , number and cover of spores.

Filaments are usually colorless and at the edge of a young culture “48 hrs” then spores begin to form accordingly we can recognize type of fungi .

In this picture we see a tomato with a white spot, this is commonly seen at home , thread like structures , related to fungi names alternaria .

If you culture it , you will see elongated cells , later they produce filaments , later these filaments branch and become fragmented.

Alternaria may damage cell wall , and food can’t be used.

Some of these alternaria might produce infections , especially in relation to sinuses in patient suffering from immune-deficiency , also following an operation , or in the eyes …. And produce localized infection.

Now return back to Opportunistic Systemic Mycoses:

Fungal infection , especially filamentous, cannot be observed In immune-competent patient or healthy or a functional system.

It can almost be seen only in immune-compromised or immune-deficiency patients and less in patients after injuries or operations , often give the

impression, especially in lungs, of developing an allergic reaction , which may manifest later in the form of asthma .

Patients age above 60 5 to 10 % they suffer from mild to severe asthma in all communities.

Some fungi may cause invasive infection especially asperigullus, and we recognize two forms :

1- Very common form in relation to the presence of granuloma lesions in respiratory tract, Can be present in the oral cavity, more common in sinuses and lungs especially if within the lung there is a cavity ex Tuberculosis or malignancies or fibrosis aspergillus produce filaments and spores and cause severe damage in lungs.

2- Rarely there will be dissemination from the respiratory tract then to the blood stream and then to the meninges cause aseptic meningitis and cannot recognize the presence of the organism and you cannot recover .It be confused with brain abscess.

Can infect external ear and produce external otitis discharge of blackness from spores of these filamentous fungi.

So the disseminated disease is rare but often fatal and patient cant be cured even with the use of anti-fungal drugs, especially aspergilloma in lungs once it’s established in lungs , we can only remove the lung in order to get rid of the infection.

Now will talk about aspergillus flavus

1- associated with the production of very highly dangerous toxin called aflatoxin.

2- Associated with food intoxication especially all type of nuts, peanuts, grains.

3- In our country the ministry of health inspect all type of food that could be infected with aspergillus flavus and aflatoxin.

4- Cause severe liver cirrhosis.5- High mortality.6- Infect humans and animals.7- We can detect it by the presence of bitterness or acid-like taste it can be

infected and contain toxin.8- Herbs and nuts if not preserved and stored in closed container without the

presence of humidity, they will be contaminated

Another disease that’s is important, it’s not common but recognizable in our countries in few cases , mostly in association with immune-compromised conditions and it’s called cryptococcosis:

1- It is cause by cryptococcos neoformans.2- encapsulated yeast3- surrounded by large capsule.4- Can be easily distinguished by india ink wet preparation.5- Can be cultured by sabouraud agar but it take a long time , 1-2 weeks to

recognize.6- Cryptococcos neoformans is found in the droppings “feces” of

birds ,pigeons (why?) because the body temperature of birds is higher than humans “41-42 c” .Any person who is immune-compromised might acquire infection, and it starts in sinuses and later might disseminate to the lungs , blood , meninges, brain and cause brain abscess these cases are difficult to detect and require a lot of investigation to recognize the presence of C. neoformans.

7- The treatment is also very difficult8- High mortality rate , might reach 100%.

We will talk histoplasmosis and blastomycosis:

1- Both excreted by birds in their feces.2- Endemic in south-western U.S.A., northern Mexico and various parts South

America.3- Dimorphic fungi means that when they infect our body , we only

recognize the yeast structure, not the complete morphological structure that contain filaments and spores.

Histoplasmosis which is caused by histoplasma capsulatum is considered a very dangerous disease in immune-compromised conditions, but in healthy people infection is often associated with asymptomatic lung infection which mean you contacted few spores , your body responded immunologically and this can be demonstrated by special test called antigen skin test for histoplasmosis , so you will have cell mediated immunity against this organism, but spores will reside exactly like tuberculosis in the infected tissue of the lungs and later if there is any wearing of the immunity or weakening in the immunity of the body , these spores might flare up, get activated and produce lesions in the form of granuloma which spread to the oral cavity mucosa , bones, skin, any part of the body … and cause fatal histoplamosis .

This is seen in less than 0.1% of exposed patients.

A second blastomyces dermatitidis in relation to the epidermis or skin the main clinical feature is not in skin but in oral cavity mucosa in the form of systemic disease.

These two type of diseases are not found in our countries but it’s important to have an idea about the lesions related to these organisms , which don’t respond easily to anti-fungal drugs.

They are often detected by pathology not by culture , because spores can be inhaled in culture and cause disease, treatment is also not easy , it might require surgical treatment , mortality is very high.

Done by: Noor hilal