micro sheet # 5 Dr. 7assan - Ruaa Rawa

Trypanosomatidae

●They are really flagellate (they have flagella by which they can move)

●These have two groups:
1) Lishmania
2) Trypanosoma
Both are cross flagellate and these actually look like the picture in page four in the hand out (however the picture is actually for lishmania)

They are Dimorphic why? Because they exist in two different morphologies one form in the primary host who is the human being, The other form found in the intermediate host which is an insect

●Figure 4-1 page four in the hand out:
Fist draw from the left this is really a macrophage cell see the nucleus, the structure inside is AMASTIGOTE
SO lishmania parasite in the human being is an intracellular
Pathogen and happens to occur inside or within the macrophage.

AMASTIGOTE: it is rounded; intracellular; there is a nucleus and small amount of DNA which known as kineto-plast has something to do with the flagella it measures about 2-3 micron.

PROMASTIGOTE: it is elongated in the intermediate host, it is extracellular, has the kineto-plast which is really at the base of the flagella (the flagella has to be anteriorly)

●The intermediate host in the lieshmania is actually a Fly which is a sand fly (page sex in the hand out) when stand up their wings will stand up found in Jordan, feeds on the blood sucking transmitting the disease from one person to another.

●There are a lot of species of leishmania BUT all these species cause four spectra of the disease (four forms):
NOTE: same organism but according to the species or geographic distribution of the disease can give different forms of the disease.

1) Cutaneous leishmaniasis, what happens?
→Sand fly comes and bite somebody (either on the face or exposed limbs) when they bite they inject their promastigote
Into the skin, these promastigote in the infected person will activate the complement system because of the activation of the complement system → deposition of the complement breakdown molecules (CD3), macrophage has CD3 receptors on their surface SO binding will undergo between CD3 and CD3 receptors on the macrophage→phagocytosis of the promastigote into the macrophage.
Once the promastigote are inside the macrophage, promastigote loss their flagella
Once the promastigote are inside the macrophage, promastigote loss their flagella and change their morphology into AMASTIGOTE and the amastigote will set within the macrophage without attack by the lysosomes at all, it is very tolerate very resistant SO it doesn't destroyed, it is start to divide within the macrophage.

Q/How we can activate the macrophage to kill the parasites?
Answer: we must do activation to them but HOW?
The only way to activate the macrophage and make them produce free oxygen radicals to kill the parasites inside them (amastigote) we need to call the help from the helper T-cells you start recruiting of T-lymphocytes and more macrophages come to the site of the infection SO what will happen?
→At the site of the infection you will get a large accumulation of cells and this accumulation will produce an induration دعدورة {induration: - abnormal hardening of a tissue or organ}
Why? Because of the cellular infiltrations. Swelling or induration will happen at the site of infection, eventually the blood supply will compromise SO it will ULCERATE. This ulcer can be dry or can be oozing with serum(moist) and will go on and on for many months towards the end it might up to one year what will happen?
→The ulcer will gradually heals, the helper cells with macrophages they did their job properly and the eradicated all the amastigote inside the macrophage, and the person will develop immunity for the rest of his life.

TO SUM UP:
Bite → Induration → Ulceration (this ulceration will go on and on for many months up to about one year) → Heal (where it heals it will produce really a disfiguring kind of scar)

Almost the bite will be on the face but also any part of the can be involve "not only the face"

NOW: when the person get the initial bite by sand fly (as we mentioned) the person will develop T1-helper response, cell mediated response, and can deal with the infection quietly
In some cases with some species when the AMSTIGOTE goes inside the macrophages you finds that the responsible body actually mediated towards antibodies production rather than cellular immunity production

Remember:
►T1-Helper response:- really concern with cell mediated Immunity "promotes the action of the macrophages for example".
►T2-Helper response:- concern with the production of antibodies.

SO in these cases the infected person will get lots and lots of antibodies against leishmania parasite with very little cellular activity, Since the antibodies can't reach inside the macrophages (the amastigote inside the macrophages) they are not really effective this is known as immune devotion, it is similar to leprosy ( مرض الجذام)

◊◊We have lepromatous and tubercloid it depends whether you have antibodies mediated response or cell mediated response,
If u have cell mediated response u will get tubercloid (it is not that bad as the lepromatous), lupromatous very destructive because we have a lot of antibodies but we don't have cell mediated response.

It is the same here, if we didn't really control the infection by leishmania through the cell mediated immunity the lesion might Spread (the initial lesion was on the face u can see lesions on the leg or arm or neck also), this clinical picture called diffuse cutanous leishmaniasis (the second form of disease or infection caused by leishmania)

If restricted to one side called Cutanous leishmanaisis
If diffuse because of the immune response (immune deviation) and the species of the leishmania which is concern, the person will get disseminated lesions over the body and this is known as diffuse cutanous leishmanaisis.

2) Muco-cutanous leishmanaisis: - mainly found in South America because it's caused by special species, the story of this phenomena the person will bite by sand fly → will get a cutanous manifestation. It will heal without any problem BUT after few months or certain period of time it will reactivated inside the body and the lesion NOW appear in the muco-cutanous junction or in the mucus membrane they involve the soft palate, buccal mucosa and can go to the naso-pharynx region and so on, the person will get ulceration and this ulceration destroy the tissue, hard palate might destroyed because of these chronic granulamatous lesions and on the top of that the patient become secondarily infected by inhalation the secretions of these lesions and go dawn into the blood producing aspiration pneumonia, this is a serious manifestation of the disease that can cause death (the first two forms of the infection, cutanous and diffuse cutanous leishmanaisis doesn't produce death, BUT muco-cutanous might be a big problem causing death to the infected person).


NOTE: believed that the species that cause cutanous, muco-cutanous and diffuse cutanous only like kind of low temperatures (as we know the temperature of the skin usually about 2-3 degrees less than the core of the body, If they go to the core body temperature they can't survive, so they don't go inside and produce disease, BUT there are some species that are more resistance to lysis through the serum complement and also they can survive at the core body temperature these species responsible for the following form(the fourth) of leishmanasis infections.

4) Visceral leishmanaisis:- the most dangerous form of the leishmania infection, we are talking about the viscera so the macrophages involve in this form are concentrated mainly in the spleen, liver, bone marrow, and lymph nodes SO , THE AMASTIGOTE that are inside the macrophages that going to produce the disease are present in the previous mentioned tissues
NOW because it is so spread inside the body it is going to produce constitutional symptoms, the patient going to be unwell, fever, anemia, loss of weight, if patients with visceral leishmanaisis leave untreated they all die within ONE year so it is very fetal disease
Refer to it (in additional to visceral leishmanaisis) as Kala-azar
(It means the black disease, since the patient will get pigmentation and look black).
These are the four varieties or manifestations of leishmanaisis.

Treatment:- Antinomy oral agent
Diagnosis:- by biopsy from the lesion on the skin, in the case of visceral leishmanaisis there are no skin lesion so we take from bone marrow, sternum


Tyypanosoma
They are mainly dimorphic (have two forms which known as trypomastigote (in human) and epimastigote (intermediate host), the intermediate host of trypanosoma is fly and known as tsetse fly.

There are two main species of trypanosoma that cause the disease (sleepness sickness)
a- Trypanosoma rhodesiense (in east regions)
b- Trypanosoma gambiense (in west regions)

The differences between the two species are:
►rhodesiense produce more sever disease (one year and the patient die)
►in the cases of rhodesiense sleep sickness there is an animal reservoir, in gambiense almost no animal reservoir

What happens?
→The person get bitten by tsetse fly → inject the epimastigote → to the blood and disseminated to lymph nodes, in the lymph nodes thy will multiply → back to the blood in large number trypomastigote by this time the patient become ill and withdrawal.
○ Unfortunately it can go the nervous system and appear in CSF by this time NO treatment, the patient will die

Diagnosis: - by blood sample, you can see trypomastigote in the blood or
You can take sample from CSF.




Toxyplasma condi
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It is coccidian like Malaria
Two cycles → Sexual reproductive cycle (in the cats always)
→ Asexual reproductive cycle

The primary host for the toxyplasma is the cat always
Sexual reproductive occur in the primary host (cats)
Where it takes place? In the gut of the cat
The product of the sexual reproductive is known as oocyst
Oocyst:- are shed with the feces of the cat
Inside the oocyst there are two small cysts and each small cyst contains four sporozoites
The oocyst eaten by intermediate host, there is no specifically for toxyplasma condi (actually it can infect many variety of tissues).
"Big variety of tissues and also big variety of animals"

In this case we will take the mouse as an intermediate host for toxyplasma condi, the mouse eat something that contaminated by cat feces and off course what will happen to these sporozoites→ they will release in the gastrointestinal tract of the intermediate host (the mouse) → will penetrate through the wall and will disseminated all over the body, in the body of the intermediate host will become intracellular.
"Toxyplasma in the body of the intermediate host is an intracellular organism".

NOW: These inside the intermediate host begin to divide and can become any type of cells(no specifically as mentioned before, high variety of tissues)
They can be liver cells, intestinal cells what ever it is.

These sporozoites actually will become trophyzoites and start dividing inside the cell as they divided inside the cell they are very active and they divide very very rapidly, because of that we called them tachyzoites (not trophyzoites) they continue in dividing until the entire cell become full by these tachyzoites, what happens? → It ruptures and releases these tachyzoites causing infection of other cells.

SOMETIMES when these tachyzoites dividing inside the cell they full it completely, then once they full completely they don't rupture and then they start show down we called them bradyzoites.

The cells of the intermediate that still intact and full with bradyzoites
Called cyst.

Remember:
►oocyst:- the result of the sexual reproductive cycle in the primary host the cat
►cyst:- are cells full with bradyzoites present in the tissue of the intermediate host.


If the mouse eaten up by another cat, what will happen?
→ these bradyzoites will release in the gut of the cat → they become like gametocytes (♀ and ♂) → joined together producing zygote → the zygote will give rise to oocyst, which will become discharge with the feces of the cat,
SO the life cycle of toxyplasma condi is complete

In relation to toxyplasma condi the human considered as an accidental intermediate host.

The human become an intermediate host and accumulate bradyzoites in his tissue BUT, Fortunately for the toxyplasma condi the human an end stage (the disease can’t transmitted from the human to the cat).

The human become an intermediate by one of the following:
→Eat oocyst OR
→Eat cyst (many animals can infected not only the mouse if the human eat meat for example he can be infected).


◊The only regions that don't have toxyplasma condi are the regions without any cats.

Infection by toxyplasma condi very common.
The majority of cases are asymptomatic, if they do they will be very mild and can't even notice.
After infection the person will become sero +ve (develop immunoglobulin's against toxyplasma) and will be fine for the rest of his/her life

BUT The problem if the lady was pregnant especially in the first trimester, if a pregnant women infect with toxyplasma for the first time, the toxyplasma can cross the placenta and cause fetus infection, this will either produce
(Abortion) or (abnormalities of the eye or CNS abnormalities).

And this known as congenital toxoplasmosis, this can only happen if the pregnant infect for the first time with toxyplasma during pregnancy.

If a woman infect for the first time during pregnancy and she has abortion or a fetus with abnormalities (congenital toxoplasmosis), the second pregnancy and the third (all the pregnancies) will be fine.

If she get the infection where she was little she will be fins, since she will develop immunity against toxyplasma for the rest of her life.

The person infect with toxyplasma will be fine It isn't that dangerous (develops immunity), unless the person is an immunocompromized patient (AIDS for example) {some people in their old age become immunocomized} then it can be reactivated.

NO vaccine for toxyplasma.
Dignosis:- by serology, we take blood sample and measure immunoglobulin against toxyplasma


Congenital toxoplasmosis:- If the baby born and we want to know whether the baby infected or not? → Take blood sample and measure antibodies against toxyplasma, in this case you must determine what class of Ig:-
IgG→ doesn't mean anything, since IgG come from the maternal
IgA→ antibodies against toxyplasma that mean the baby get a recent infection by toxyplasma





THE END..
Done by; Ruaa Rawa
Date of the lec: 12/4
Doctor: Hassan



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