Transcript Toxoplasmosis

 Introduction
 Epidemiology
 Pathogenesis
 Causes
 Risk factors
 Signs and Symptoms
 Prevention
 Diagnosis
 Management
 Complications
 Case study
 References
Introduction
Toxoplasmosis is a parasitic disease
caused by the protozoan Toxoplasma
gondii. The parasite infects most
genera of warm-blooded animals,
including humans, but the primary
host is the felid (cat) family. Animals
are infected by eating infected meat,
by ingestion of feces of a cat that has
itself recently been infected, and by
transmission from mother to fetus.
Cats are the primary source of
infection to human hosts, although
contact with raw meat, especially
lamb, is a more significant source of
human infections in some countries.
Epidemiology
T. gondii infections occur throughout the world,
although infection rates differ significantly by
country. For women of childbearing age, a survey
of 99 studies within 44 countries found the areas
of highest prevalence are within Latin America
(about 50–80%), parts of Eastern and Central
Europe (about 20–60%), the Middle East (about
30-50%), parts of Southeast Asia (about 20–60%),
and parts of Africa (about 20–55%).
Types
There are types I, II, and III.
These three types of T. gondii have differing effects on certain
hosts, mainly mice and humans due to their variation in
genotypes.
Type I: virulent in mice and humans, seen in AIDS patients.
Type II: non-virulent in mice, virulent in humans (mostly Europe
and North America), seen in AIDS patients.
Type III: non-virulent in mice, virulent mainly in animals but
seen to a lesser degree in humans as well.
Because the parasite poses a particular threat to fetuses when it
is contracted during pregnancy, much of the global
epidemiological data regarding T. gondii comes from
seropositivity tests in women of childbearing age. Seropositivity
tests look for the presence of antibodies against T. gondii in
blood.
Pathogenesis
T. gondii Survival Mechanisms
Once the plasmid T. gondii infects a normal host cell, it resists
damage caused by the host’s immune system, as well as
changing the host's immune processes.
One way is by an anti-apoptotic mechanism, allowing the
infected host cells to persist and replicate. One method of
apoptosis resistance is by disrupting pro-apoptosis effector
proteins, such as Bax and Bak. In order to disrupt these proteins,
T. gondii causes conformational changes to the proteins. T.
gondii does not, however, cause downregulation of the proapoptosis effector proteins.
T. gondii also has the ability to initiate autophagy of
the host’s cells. This leads to a decrease in healthy,
uninfected cells, and consequently less host cells to
attack the infected cells. Research by Wang et al finds
that infected cells lead to higher levels of
autophagosomes in normal and infected cells. Their
research reveals that T. gondii causes host cell
autophagy using a calcium-dependent pathway.
Another study suggests that the parasite can directly
affect calcium being released from calcium stores,
which are important for the signalling processes of
cells.
Causes
 Contact with cat feces that contain the parasite.
Cats who hunt or who are fed raw meat are most
likely to harbor T. gondii.
 Eating contaminated food or drink contaminated
water. Lamb, pork and venison are especially
likely to be infected with T. gondii. Occasionally,
unpasteurized dairy products also may contain
the parasite.
 Use of contaminated knives, cutting boards or
other utensils.
 Eating unwashed fruits and vegetables.
 Receiving an infected organ transplant or
transfused blood. In rare cases, toxoplasmosis
can be transmitted through an organ transplant
or blood transfusion.
Risk factors
 HIV/AIDS. Many people with HIV/AIDS also have toxoplasmosis.
In some cases, the infection is recent, and in others, an old
infection has become active again.
 Chemotherapy. Chemotherapy affects your immune system,
making it difficult for your body to fight even minor infections.
 Steroids or other immunosuppressant drugs. Medications used to
treat certain nonmalignant conditions suppress your immune
system and make you more likely to develop complications of
toxoplasmosis.
 Pregnancy: If you have active toxoplasmosis, treatment can
reduce the risk to your baby. If you've already had toxoplasmosis
before becoming pregnant, you generally can't pass the infection
to your baby.
 Fecal contamination of hands is a significant risk factor.
Signs and symptoms
Infection has three stages:
 Acute toxoplasmosis
During acute toxoplasmosis, symptoms are often
influenza-like:
0 swollen lymph nodes
0 muscle aches and pains that last for a month or
more.
Young children and immunocompromised people,
such as those with HIV/AIDS, those taking certain
types of chemotherapy, or those who have
recently received an organ transplant, may
develop severe toxoplasmosis.
The toxoplasmic trophozoites causing acute
toxoplasmosis are referred to as Tachyzoites, and
are typically found in bodily fluids.
Latent toxoplasmosis
In most immunocompetent people, the
infection enters a latent phase, during
which only bradyzoites are present,
forming cysts in nervous and muscle
tissue. Most infants who are infected while
in the womb have no symptoms at birth,
but may develop symptoms later in life.
Cutaneous toxoplasmosis
0 roseola and erythema multiforme-like
eruptions
0 prurigo-like nodules
0 Urticaria
0 maculopapular lesions
0 Newborns may have punctate macules,
ecchymoses, or “blueberry muffin”
lesions.
Prevention
 Wear gloves when gardening, particularly when handling soil.
Also, be sure to wash your hands thoroughly afterwards with
soap and hot water.
 Do not eat raw, or undercooked, meat, particularly lamb,
pork, and venison, including any ready-prepared chilled
meals.
 Avoid sheep and their newborns during the lambing season if
you are at extra risk.
 Wash all kitchenware thoroughly after preparing raw meat.
 Wash all fruits and vegetables before cooking and eating,
including ready-prepared salads.
 Avoid un-pasteurised goat's milk or products that are made
from it.
 Do not handle or adopt stray cats.
 Avoid cat faeces in cat litter or soil. Wear gloves if you are
changing a cat litter tray, and if you are pregnant, or immune
deficient, ask someone else to do this for you.
 Feed your cat dried, or canned, cat food, rather than raw
meat.
Don’t!!!
Do
Diagnosis
Diagnosis of toxoplasmosis in humans is made by biological, serological,
histological, or molecular methods, or by some combination of the above.
Detection of T. gondii in human blood samples may also be achieved by
using the polymerase chain reaction. Inactive cysts may exist in a host
that would evade detection.
Several serological procedures are available for the detection of T. gondii
antibody in patients, which may aid diagnosis; these include the SabinFeldman dye test (DT), the indirect hemagglutination assay, the indirect
fluorescent antibody assay (IFA), the direct agglutination test, the latex
agglutination test (LAT), the enzyme-linked immunosorbent assay
(ELISA), and the immunosorbent agglutination assay test (IAAT). The IFA,
IAAT and ELISA have been modified to detect immunoglobulin M (IgM)
antibodies.
IgG antibody
The most commonly used tests for the measurement of IgG antibody are the DT, the
ELISA, the IFA, and the modified direct agglutination test. These tests reveal that
IgG antibodies usually appear within 1–2 weeks of acquisition of the infection, peak
within 1–2 months, decline at various rates, and usually persist for life.
Acute infections can be differentiated from chronic infections using the
“differential” agglutination test (also known as the AC/HS test), which is best used
in combination with a panel of other tests such as the TSP. The AC/HS test results
when parasites are fixed for use in the agglutination test with two different
compounds (i.e., acetone and formalin). The different antigenic preparations vary in
their ability to recognize sera obtained during the acute and chronic stages of the
infection.
IgM antibody
The most commonly used tests for the measurement of IgM antibody are doublesandwich or capture igM-ELISA kits, the IFA test, and the immunosorbent
agglutination assay (IgM-ISAGA). Commercial test kits often have low specificity,
and the reported results are frequently misinterpreted. The IgM antibodies appear
sooner after infection than the IgG antibodies and disappear faster than IgG
antibodies after recovery.
Congenital toxoplasmosis
A whole set of recommendations applies for the diagnosis of congenital
toxoplasmosis: i) prenatal diagnosis based on molecular testing of
amniotic fluid and ultrasound examinations; ii) molecular testing of
placenta and cord blood, comparative mother-child serologic tests and
a clinical examination at birth; iii) neurologic and ophthalmologic
examinations and a serologic survey during the first year of life.
Toxoplasmosis cannot be detected with immunostaining. Lymph nodes
affected by Toxoplasma have characteristic changes, including poorly
demarcated reactivegerminal centers, clusters of monocytoid B cells,
and scattered epithelioid histiocytes.
Diagnosis of cutaneous toxoplasmosis is based on the tachyzoite
form of T. gondii being found in the epidermis. It is found in all levels of
the epidermis, is about 6 μm by 2 μm and bow-shaped, with the
nucleus being one-third of its size. It can be identified by electron
microscopy or by Giemsa staining tissue where the cytoplasm shows
blue, the nucleus red.
Treatment
Acute
The medications prescribed for acute toxoplasmosis are the following:
 Pyrimethamine — an antimalarial medication
 Sulfadiazine — an antibiotic used in combination with pyrimethamine
to treat toxoplasmosis
 Combination therapy is usually given with folic acid supplements to
reduce incidence of thrombocytopaenia.
 Combination therapy is most useful in the setting of HIV.
 Clindamycin
 Spiramycin — an antibiotic used most often for pregnant women to
prevent the infection of their children
 (other antibiotics, such as minocycline, have seen some use as a salvage
therapy).
Latent
In people with latent toxoplasmosis, the cysts are immune to these
treatments, as the antibiotics do not reach the bradyzoites in sufficient
concentration.
The medications prescribed for latent toxoplasmosis are:
 Atovaquone — an antibiotic that has been used to kill Toxoplasma
cysts inside AIDS patients
 Clindamycin — an antibiotic that, in combination with atovaquone,
seemed to optimally kill cysts in mice
 Trimethoprim/sulfamethoxazole is the drug of choice to prevent
toxoplasmosis, but not for treating active disease.
Complications
Ocular toxoplasmosis causes ocular lesions, which are wounds in
the eyes caused by inflammation and scarring. These can appear in
the:
retina – the light-sensitive layer of tissue at the back of the eye
choroid – the layer behind the retina that contains major blood
vessels
This damage to the eyes is called retinochoroiditis and can cause
eye problems, such as:
 a partial loss of eyesight in one eye
 squint – where one eye looks in a slightly different direction to
the other one
 clouding of the eye's lens (cataracts)
 eye shrinking (microphthalmia)
 loss of cells and tissue from the optic nerve, which connects the
eye to the brain, resulting in poor vision (optic atrophy)
 Infants infected via placental transmission may be born with
either of these problems, or with nasal malformations, although
these complications are rare in newborns.
Antibiotics and steroids are often used to treat the lesions. The scarring caused
by toxoplasmosis will not clear up, but treatment may prevent it from getting
worse.
Congenital toxoplasmosis
In most cases, babies born with congenital toxoplasmosis develop normally after
treatment with antibiotics.
However, in up to 4% of cases, serious complications can develop within the first
years of life. These include:
 permanent visual impairment (partial or, very rarely, complete sight loss)
 permanent brain damage
 Death
Cases of ocular toxoplasmosis can also occur years after infection. One study
found the average age at which it appeared was nine years old.
It's also possible for someone to develop complications in their 20s or 30s.
These may include:
 learning disabilities
 hearing loss
 ocular toxoplasmosis
Encephalitis-toxoplasmosis can lead to seizures
and life-threatening illnesses such as encephalitis
— a serious brain infection. In people living with
AIDS, untreated encephalitis resulting from
toxoplasmosis is fatal. Relapse is a constant
concern for immunocompromised people with
toxoplasmosis.
Clinical case
A 50-year-old woman presented with sudden onset of decreased vision in
her better left eye. She had 1 week of redness, photophobia, pain, and
decreased vision. She reported no underlying systemic disease or recent
health change and no family history of unusual eye disease. (She was 1 of 8
siblings with the same biological parents.) She was not on medication. She
did report an allergy to sulfur medicines that have given her "a bad rash."
Of most significance was the fact that she had developed severe vision loss
in her right eye about 20 years prior from recurrent attacks "from some
type of parasite" in her native country of Brazil. She said that she grew
up with a lot of cats that roamed the outdoors and that her family had
lived in several regions of Brazil. Her right eye was damaged in a motor
vehicle accident at some point after it had developed very poor vision
from the parasitic infection. She immigrated to the United States about
10 years ago with her husband.
On examination, her visual acuity was light perception in her
right eye and 20/100 in her left eye. Her intraocular
pressures were 4 mm Hg in her right eye and 14 mm Hg in
her left eye. There was no view of the anterior chamber of
her right eye secondary to an opaque cornea. However, she
had 2+ cell and flare of her left eye. In addition, she had
several keratic precipitates in her left eye that were fresh in
appearance. There was no view of the posterior pole of her
right eye, and an ultrasound was unremarkable, including the
lack of any vitreal debris. The vitreous of her left eye had 1+
anterior vitreal cells (with more cells in the posterior
vitreous) with some macular edema. Initially, it was difficult
to get a complete view of her fundus, but it did appear that
there was a focal white area in the superior nasal left fundus
adjacent to a darker area.
Her chest x-ray was normal. In addition, fluorescent
treponemal antibody, complete blood cell count, Creactive protein, erythrocyte sedimentation rate,
Lyme, and Bartonella assays were negative. A recent
physical exam by her internist, including a purified
protein derivative (tuberculin), was negative.
However, Toxoplasma gondii immunoglobulin
(Ig)G returned with a high positive titer.
References
www.mayoclinic.org
www.hse.ie
http://www.nhs.uk/
http://en.wikipedia.org/
https://www.google.com
http://www.medscape.org/
http://www.kellogg.umich.edu/