TOXOPLASMOSIS

Nelson A. Salazar, M.Sc., DLSHTM, Ph.D.

Fig. 1. Global status of Toxoplasma gondii seroprevalence. Dark red
equals prevalence above 60%, light red equals 40–60%, yellow 20–
40%, blue 10–20% and green equals prevalence <10%. White equals
absence of data.
Intermediate host: birds, Tachyzoites (trophozoites) infect all
mammals, humans nucleated cells in the host, replicate
and cause tissue damage

Bradyzoites (slow
growing form observed
within tissue cysts)
encyst within
the CNS and muscle of
the infected host

Definitive host

Life cycle of
toxoplasmosis
Oocysts are excreted in cat feces.
Contaminated soil is ingested by birds,
mammals and humans.
 Life cycle of Toxoplasma gondii

The three stages of this obligate intracellular

parasite are:

(i) Tachyzoites (trophozoites), which rapidly proliferate and

destroy infected cells during acute infection. They are
pressured by the hosts immune response to transform into
bradyzoites.

(ii) Bradyzoites, which slowly multiply in tissue cysts, most

commonly in skeletal muscle, myocardium, and brain. They
may remain throughout the life of the host.

(iii) Sporozoites in oocysts (Fig. 1).

Fig.1 The Toxoplasma lytic cycle and basic tachyzoite
organization. (a) The lytic cycle of invasion, replication, and egress. (b)
Organelles in the secretory pathway are shown in white and the secretory
organelles themselves in three shades of blue. Abbreviations: EC, endosome
compartment; ER, endoplasmic reticulum; IMC, inner membrane complex;
PLV, plant-like vacuole.
Fig. 1 Three life stages of Toxoplasma gondii

Tachyzoites Cyst with Bradyzoites Sporulated Oocysts

(Giemsa stain) In brain tissue
Toxoplasma gondii. Fig. 2 LM of Toxoplasma gondii. Fig. 3 LM
tachyzoites of T. gondii (they of a tissue-cyst (filled with
develop by endodyogen bradyzoites).
(asexually) in macrophages).
Toxoplasma gondii—Tachyzoite. Arrow points to a
tachyzoite of Toxoplasma gondii in cardiac muscle.
 Risk factors

• Eating raw or undercooked pork, lamb, beef, minced meat

products, oysters, clams, mussels.

• Eating raw or unwashed vegetables or fruits

• Contact with soil (gardening and yard work)

• Kitten ownership

• Cleaning the cat litter box

Fig. 1. Relative importance of food-related transmission of T. gondii
to humans. Adapted from the Report of the WHO Consultation
on Public Health Aspects of Toxoplasmosis and from several studies.
 Risk factors

Once infected with Toxoplasma is my cat always able

to spread the infection to me?

No, cats only spread Toxoplasma in their feces for a few weeks
following infection with the parasite.

Like humans, cats rarely have symptoms when infected, so most

people do not know if their cat has been infected.

The Toxoplasma shedding in feces will go away on its own;

therefore it does not help to have your cat or your cat's feces
tested for Toxoplasma.
 Transmission

Human infection may be acquired in several ways:

1. Ingestion of tissue cysts in meat from an infected animal.

2. Ingestion of infectious oocysts from the environment (usually from

soil contaminated with feline feces)

3. Organ transplantation or blood transfusion

4. Through vertical transmission from an infected mother to her fetus

5. Accidental inoculation of tachyzoites.

The two major routes of transmission of Toxoplasma to humans are

oral and congenital.
 P a t h o l o g y o f Toxoplasma gondii

Fig. 4. Illustration of mechanism implicated in apoptosis-PCD induced by

Toxoplasma gondii. Several host proteins involved in apoptosis, modulated
by parasites, were identified using a combination of two-dimensional
electrophoresis (2DE), difference gel electrophoresis (DIGE), and mass
spectrometry (MS).
Figure 1. Crossing of the blood-brain barrier (BBB) by parasites associated with
WBCs. (A) Illustration of a cerebral post-capillary vessel showing the BBB,
consisting of a complex of cerebral endothelial cells and their tight junctions,
basement membranes and pericytes as well as astrocytic end-feet.
Note the perivascular space that is noticeable during inflammation.
Clinical forms of Toxoplasmosis
 Clinical manifestations

Toxoplasmosis can be categorized into four groups:

• (i) acquired in the immunocompetent patient

• (ii) acquired or reactivated in the immunodeficient patient
• (iii) congenital
• (iv) ocular

Methods of diagnosis and their interpretations may differ for

each clinical category.

Once a person is infected, the parasite lies dormant in neural

and muscle tissue and will never be eliminated.
 Clinical manifestations

• The most common manifestation in symptomatic

infection is bilateral, symmetrical cervical adenopathy.

• Congenital infection can result in abortion or neonatal

disease with encephalitis, chorioretinitis, and
hepatosplenomegaly.

• Fever, jaundice, and intracranial calcifications.

Toxoplasmic encephalitis in a 36-year-old patient with
AIDS. The multiple lesions are demonstrated by magnetic
resonance scanning.
 Clinical manifestations

• Most infected newborns are asymptomatic, but

chorioretinitis or mental retardation will develop in some
children months or years later.

• Congenital infection with Toxoplasma is one of the

leading causes of blindness in children.

• In patients with reduced cell-mediated immunity (e.g.,

AIDS patients), life-threatening disseminated disease,
primarily encephalitis, occurs.
 Clinical Manifestations (Congenital
toxoplasmosis)

• Congenital toxoplasmosis has a broad spectrum of

nonspecific clinical manifestations.

• The so-called classic triad of congenital toxoplasmosis

consists of chorioretinitis, hydrocephalus, and
intracranial calcifications.

• However, the classic triad occurs in fewer than 10

percent of cases.

• Most newborns with congenital toxoplasmosis are

asymptomatic.
 Hydrocephalus in congenital toxoplasmosis

The infection typically produces calcification of the subependymal

tissues, and sometimes dilatation of the ventricules due to rapid
proliferation of the parasites. There is serious cerebral damage.
 Generalized clinical manifestations of
congenital toxoplasmosis

hepatosplenomegaly, jaundice, and thrombocytopenic

purpura.
 Ocular toxoplasmosis (i)

• It may be the result of congenital or acquired infection.

• Inflammation of the retina and choroid (retinochoroiditis)

is the most frequent, permanent manifestation of
toxoplasmic infection.

• Clinical manifestations are much more common and

severe in Latin America when compared with Europe
and USA.
– Eye lesions were larger and numerous in Brazilian newborns
than in European newborns.
Fig. 1 Burden of ocular and neurological disease in congenital
toxoplasmosis of children under six years of age with various
ethnogeographic backgrounds.
Table 2 Congenital toxoplasmosis in Europe and Southern
America.
 Ocular toxoplasmosis (ii)

Clinical Manifestations:

The patient may present with

• Floaters (vitritis)
• Decreased vision
• Pain
• Redness
• Photophobia
Fig. 2 Functional consequences of ocular toxoplasmosis.
An impairment of the visual field is much more common than a reduction
in visual acuity (94.2% versus 40.5%) in European individuals.
Congenital ocular toxoplasmosis
 Acquired ocular toxoplasmosis

Fig. 3 Fundus photographs and fluorescent angiograms of a 27-

year-old soldier with recurrent ocular toxoplasmosis on initial
presentation (A), first attack finding (B), and second attack finding
(C). Note that recurrent lesions were located near the pre-existing
scar.
Pre- and post-treatment retinochoroiditis

In retinochoroiditis, funduscopic examination shows

vitreous inflammatory reaction, white retinal lesions,
and pigmented scars.
T. gondii is the most common parasite in developed nations,
according to Schizophrenia Bulletin. The cat-carried parasite can
infect any warm-blooded species, and the Centers for Disease
Control and Prevention estimates more than 60 million people in
the U.S. may have it.
Obsessive–compulsive disorder (OCD) is a mental disorder where people feel
the need to check things repeatedly, perform certain routines repeatedly
Toxoplasma image: Visualising Toxoplasma modifying its host cell. All human
cells in red and Toxoplasma parasites in purple. Toxoplasma changes the cell
that it is living within, here represented by a change in colour from red to
green. Dr Chris Tonkin pictured right. Credit: Chris Tonkin/Walter and Eliza Hall Institute
People infected with
Toxoplasma gondii
are more likely to be
involved in car
accidents due
the intermittent
explosive disorder
caused by this
parasite.
 Diversity among Toxoplasma gondii strains

1. The majority of the T. gondii strains isolated from North

America, Europe, Asia and Africa are distributed
into three major groups: type I, II and III lineages.

2. Strains isolated in South America showed a higher genetic

variability with distinct genotypes, with high rates
of transmission and outcrossing.

These strains were not identified in North America, Europe,

Asia or Africa.
Table 2 Summary of the molecular approaches used for
detection and genetic characterization of Toxoplasma gondii
 DIFFERENTIAL DIAGNOSIS

Acute toxoplasmosis may be mistaken for acute

Epstein-Barr virus or cytomegalovirus infection,
especially since mild atypical lymphocytosis can be
seen with toxoplasmosis.

Many of the symptoms of acute toxoplasmosis overlap

with the symptoms of HIV infection (eg, fever and
generalized lymphadenopathy)
 Flujograma de atencion
para el diagnostico y
tratamiento de la
toxoplasmosis durante el
embarazo
 Treatment

In general, physicians treat T. gondii infection in four

circumstances:

(1) pregnant women with acute infection to prevent fetal

infection.

(2) congenitally infected infants.

(3) immune-suppressed persons, usually with

reactivated disease.

(4) acute and recurrent ocular disease.

1. Treatment to prevent fetal infection
 2. Treatment of fetal infection

Folinic acid in the form of leucovorin calcium must be given to protect

the bone marrow from the toxic effects of pyrimethamine.
2. Treatment of newborn infection
 4. Treatment of immuno-suppressed
persons
• In immunosuppressed persons with toxoplasmosis, a
regimen of pyrimethamine and sulfadiazine plus
leucovorin is the first line treatment of choice.

• Clindamycin is a second alternative for use in

combination with pyrimethamine and leucovorin in those
who cannot tolerate sulfonamides.

• Atovaquone in combination with either pyrimethamine or

sulfadiazine has sufficient activity to be considered for
treatment in some less severely affected adult patients
 5. Treatment of Ocular Toxoplasmosis (OT)

Most cases of ocular toxoplasmosis do not need treatment since

they represent inactive disease and/or scarring.

The decision to treat acute disease depends upon several factors,

including:

• the degree of inflammation

• the patient’s visual acuity, and
• the size, location and persistence of the lesion.

Pyrimethamine + sulfadiazine + corticosteroids is the most commonly

used combination of drugs for the treatment of OT and may be
considered the classic therapy.
Cook meats to adequate
temperatures:

• meat ≥ 63°C (3 min)

• ground meat ≥ 71°C
• poultry ≥ 74°C
Toxoplasmosis- Mitos y Realidades (Objeto Virtual de
Aprendizaje-OVA)-Nelson Arturo Salazar Buitrago

http://temas.s3.amazonaws.com/rosario/mutis/micrositiomuti
s/ova.htm