Toxoplasmosis

Toxoplasmosis
The right clinical information, right where it's needed
Last updated: Jul 05, 2019

Table of Contents
Summary 3
Basics 4
Definition 4
Epidemiology 4
Aetiology 4
Pathophysiology 5
Classification 5
Prevention 7
Primary prevention 7
Screening 7
Secondary prevention 8
Diagnosis 9
Case history 9
Step-by-step diagnostic approach 9
Risk factors 12
History & examination factors 13
Diagnostic tests 15
Differential diagnosis 17
Treatment 21
Step-by-step treatment approach 21
Treatment details overview 24
Treatment options 27
Emerging 38
Follow up 39
Recommendations 39
Complications 39
Prognosis 40
Guidelines 42
Diagnostic guidelines 42
Treatment guidelines 42
Online resources 44
References 45
Images 50
Disclaimer 55
Summary
◊ A protozoan parasite spread through food or water contaminated with oocysts, through infected meat
or through contact with oocysts from feline faeces.
◊ Acute infection is usually asymptomatic, and once acquired, parasites remain in human tissues life-
long.
◊ Symptomatic disease can be seen in immunocompromised patients with re-activation of latent

infection or with acquisition of new infection.
◊ Symptomatic eye disease can be seen in both immunocompromised and immunocompetent

patients.
◊ Primary infection during pregnancy is often asymptomatic in the mother, but can result in congenital
disease in the fetus.
Toxoplasmosis Basics
Definition
Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii . Cats are the definitive hosts for
the parasite, and can excrete millions of oocysts, which survive in the environment for months. Humans
BASICS
are intermediate hosts, and become infected by ingesting uncooked meat infected with tissue cysts
(bradyzoites), by ingestion of other food or water contaminated with oocysts, or by transplacental spread of
tachyzoites.[1] Once bradyzoites or oocysts are ingested, or tachyzoites have spread through the placenta to
a fetus, T gondii rapidly travels to tissues and organs where it encysts and remains permanently. Infection in
humans is life-long and often asymptomatic, unless a patient becomes immunosuppressed.
Epidemiology
Toxoplasma gondii occurs worldwide, with a higher incidence in tropical areas. In the US, from 2009 to 2010
there was 10.1% seroprevalence in people 12 to 49 years old, a decrease from 1988 to 1994, at which it
was 16%.[2] Seroprevalence in southern Europe is as high as 54%, which is thought to be due to ingestion
of undercooked meat and poor kitchen hygiene. Seroprevalence in South America is also high, ranging
from 43% to 73%, probably because of the effect of waterborne transmission, in addition to ingestion of
undercooked meat. Age-specific prevalence has been decreasing in Europe over the past 30 to 40 years.[3]
Seroprevalence is low in most Asian countries (1% in pregnant women in Korea, 10% in HIV-positive
patients in Taiwan), although India (45%) and Malaysia (56%) have higher prevalence rates.[3] Rates of
seroconversion in non-immune pregnant women range from 2.4 to 16 per 1000 in Europe;[4] in the UK the
estimated rate is 2 per 1000.[5] In the US about 5 per 1000 non-immune women may acquire Toxoplasma
during pregnancy, and the prevalence of congenital disease ranges from 1 to 10 per 10,000 live births.[6]
Without treatment, infection during pregnancy results in congenital disease roughly 44% of the time, and
appropriate treatment during pregnancy lowers the risk of congenital infection to 29%.[7] [8]
In Europe and North America there are 3 main strains of T gondii , types I, II, and III, with type I being the
most virulent and type III the least virulent. Type II is the most frequent strain seen in human disease in
Europe and North America.[9] Parasites with a more diverse genetic background cause human disease in
South America, Africa, and Asia.[10] [11] [12]
Aetiology
Cats are the definitive hosts for Toxoplasma gondii , shedding large numbers of oocysts in their faeces.
Other warm-blooded animals, including humans and animals consumed by humans, develop tissue cysts
(bradyzoites) after exposure but do not spread infection via faeces. Humans are infected after eating
undercooked meat (usually pork or lamb) containing tissue cysts, or water or food contaminated with
oocysts from cat faeces. Eating raw minced beef, rare lamb, locally produced cured, dried, or smoked meat,
unpasteurised goat's milk, and raw oysters, clams, and mussels, working with meat, and having 3 or more
kittens have all been identified as specific risk factors.[13] Often the specific route of transmission cannot be
established because infection is usually inadvertent. In the US and similar countries the risk of exposure from
ingestion of undercooked meat is much greater than from handling cat faeces since many domesticated cats
are not feral and oocyst shedding is of limited duration in cats.
After T gondii oocysts or bradyzoites are ingested, they spread haematogenously from the gastrointestinal
tract throughout the human body in tachyzoite form. Tachyzoites invade cells in a variety of tissues, causing
a strong inflammatory response and tissue destruction. Tachyzoites encyst in tissues and organs days after
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infection under pressure from the host's immune response. Although tissue cysts may develop in visceral
organs, they are more prevalent in neural and muscular tissues.[14] Symptomatic disease results from re-
activation of intracellular bradyzoites into tachyzoites, which are able to leave the host cell, invade new cells,
and disseminate. Local inflammatory response at the site of tissue cyst conversion to tachyzoite form can
BASICS
result in symptomatic disease that correlates to the site of conversion (i.e., conversion of bradyzoites to
tachyzoites in the eye causes chorioretinitis and in the brain causes lesions that appear ring-enhancing on
computed tomography or magnetic resonance imaging).
Congenital toxoplasmosis results when tachyzoites in an acutely infected pregnant woman traverse the
placenta to the fetus.
Pathophysiology
In immunocompetent adults and children, primary infection is asymptomatic in most cases, but up to 10%
may have symptomatic infection. Most symptomatic infections present as isolated, non-tender cervical or
occipital lymphadenopathy. Rarely, myocarditis, myositis, pneumonitis, hepatitis or encephalitis can arise in
otherwise healthy people. Acute infection in pregnant women is often asymptomatic.[6]
Generally in congenital disease, only infections acquired in the first trimester result in fetal death and severe
congenital abnormalities such as intellectual disability and blindness. These are thought to result from
proliferation of the tachyzoite form unchecked by the immature immune system of the fetus.
Fetal infections in the third trimester are often asymptomatic at birth, but the majority of these congenitally
infected children (up to 85%) develop retinitis, central nervous system problems (such as learning disabilities
or seizures) or delayed growth months to years later.[15]
In ocular disease, focal white retinal lesions surrounded by an intense vitreous inflammatory reaction
characterise chorioretinitis. It can result from re-activation of latent disease in congenitally acquired infections
and in the immunosuppressed, or from primary infection (often associated with waterborne outbreaks), and
has a high rate of recurrence.[6]
Toxoplasmosis may be the initial opportunistic infection in HIV-positive hosts who are unaware of their HIV-
positive status. Encephalitis, the most common clinical manifestation of Toxoplasma gondii infection in
HIV-infected patients, results from re-activation of dormant encysted bradyzoites that goes unchecked by a
weakened immune system. Disseminated or organ-specific disease may also result in recipients of organ
transplants, either because of re-activation of latent infection in the recipient or because of re-activation of
latent infection in the transplanted organ.[16]
Both innate and adaptive immune mechanisms control T gondii infection. Interleukin-12 and interferon-
gamma produced by cells of the innate immune system elicit a strong adaptive Th1-biased immune
response. Natural killer cells[17] and dendritic cells[18] are important both for activation of T cells and for
control of the inflammatory response.[19] Interferon-gamma-producing CD4+ and CD8+ T cells are critical for
resolution of acute infection and for control of latent, chronic infection.[20] Inflammatory monocytes recruited
to sites of infection also play a role in disease control independent of the Th1 response by secreting nitric
oxide, which inhibits parasite growth.[21]
Classification
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jul 05, 2019.
5
Clinical presentation
Asymptomatic infection: in immunocompetent patients, 90% of infections are asymptomatic.
Disseminated disease: seen in HIV-infected patients, organ transplant recipients, or any

BASICS
immunocompromised patient.
Toxoplasma encephalitis: rarely seen in anyone other than the immunosuppressed. More commonly seen in
HIV-infected patients than in transplant recipients or others with immunosuppression.
Toxoplasma chorioretinitis: may be seen in congenital disease, immunosuppressed patients, and

immunocompetent patients. Is associated with waterborne spread of disease.
Toxoplasmosis Prevention
Primary prevention
Meats, especially lamb, pork, and venison, should be thoroughly cooked (temperature above 66°C/150°F).
Freezing meat to at least -20°C/-4°F is also effective, although most home freezers do not reach this low
temperature. Fruits and vegetables should be thoroughly washed before being eaten raw. Hands should be
washed thoroughly after gardening or other contact with soil. Avoid changing cat litter boxes; if unavoidable,
hands should be thoroughly washed after changing litter.[27] Keep cats indoors, do not allow them to hunt,
and do not feed them raw or undercooked meat.[22]
Screening
HIV-infected patients
All HIV-infected patients should be tested for prior exposure by measuring anti- Toxoplasma IgG. If the
patient was previously seronegative and is unable to take trimethoprim/sulfamethoxazole for Pneumocystis
jiroveci prophylaxis, serology should be repeated when the CD4+ T lymphocyte count nears 100 cells/
microlitre.[37]
PREVENTION
Patients with HIV and CD4+ T lymphocyte counts <100 cells/microlitre with detectable anti- Toxoplasma IgG
are at risk for re-activation of latent infection and should receive prophylactic treatment.[22]
Before antiretroviral therapy (ART) was available, patients who were seropositive for Toxoplasma and
who had advanced immunosuppression but were not receiving chemoprophylaxis had incidence rates
of symptomatic disease of 12% to 47%.[23] [24] Incidence and associated mortality has decreased
substantially since the availability of ART and initiation of prophylactic regimens.
Transplant recipients
In the US, Toxoplasma IgG testing is now required for all donors, regardless of organ.[38]
Among organ transplant recipients, toxoplasmosis is most commonly seen in heart recipients.[25] Thus,
the serostatus of all heart donors and recipients should be checked prior to transplantation.[25] Cardiac
transplant patients who have detectable anti- Toxoplasma IgG or who are recipients of hearts from
seropositive donors should receive prophylaxis.
All recipients of allogeneic haematopoietic stem cell transplants should have baseline anti- Toxoplasma IgG
testing. Prophylaxis prior to haematopoietic stem cell transplantation is recommended for all Toxoplasma
seropositive recipients.[39]
Consideration should be given to performing a polymerase chain reaction (PCR) at regular intervals for
screening purposes in patients who are at high risk of disseminated disease (e.g., heart or allogeneic
haematopoietic stem cell transplant recipients). While there is no consensus on the optimal treatment of
patients who are asymptomatic and PCR positive (i.e., trimethoprim/sulfamethoxazole prophylaxis versus
treatment dosing of pyrimethamine plus sulfadiazine), centres utilising this strategy have higher survival rates
than centres that do not screen with PCR.[36]
Pregnant women and newborns

Routine screening of pregnant women for toxoplasmosis is not recommended in the UK because the risks
may outweigh the potential benefits.[40] The American College of Obstetricians and Gynecologists does not
recommend universal screening for women of childbearing age or those who are already pregnant.[41] Some
countries with a higher seroprevalence for Toxoplasma gondii , such as France, perform routine screening
for women of childbearing age and during pregnancy.
Certain US states (Massachusetts and New Hampshire) screen for toxoplasmosis in newborns by checking
anti- Toxoplasma IgM.[42]
7
Toxoplasmosis Prevention
Secondary prevention
All immunocompromised patients with symptomatic disease should follow the 6 or more weeks of initial
therapy with secondary prophylaxis/suppressive therapy.
All seronegative immunocompromised patients and pregnant women should be counselled on avoidance
of exposure to contaminated food by thorough washing of fruits and vegetables, cooking meat to a high
temperature, and to avoid exposure to infected cats by not handling their faeces.
PREVENTION
Toxoplasmosis Diagnosis
Case history
Case history #1
A 45-year-old man with HIV (CD4+ T lymphocyte count 55 cells/microlitre) and poor medical follow-up
presents with fever, confusion, right hemiplegia, and slurred speech. He is taking no medications. A
computed tomography scan with intravenous contrast of the head reveals multiple ring-enhancing lesions
with surrounding vasogenic oedema. Ophthalmological examination reveals retinitis. Cerebrospinal fluid
bacterial antigen panel is negative and serum has detectable anti- Toxoplasma IgG.
Case history #2
A 25-year-old woman in her third trimester of pregnancy is found to have positive serology for anti-
Toxoplasma IgG. No previous serological profiles are available. She reports no recent illnesses, and has
no significant medical history. She reports taking care of several cats at home, and frequently changes
their litter. Her physician then checks for anti- Toxoplasma IgM, which is positive. Sonogram of the fetus
shows no abnormalities.
Other presentations
Symptomatic disease can manifest itself as cervical or occipital lymphadenopathy with or without fever, or
as ocular chorioretinitis.
Atypical presentations include transverse myelitis, polymyositis, myocarditis, pneumonitis or disseminated

disease with fever, and bone marrow suppression. Myocarditis can present as chest pain and heart failure
and can be mistaken for myocardial infarction. It may also present with pericarditis, arrhythmias, heart
block, or sudden death. Myocarditis can occur as re-activation of disease in immunocompromised hosts
(because of AIDS, solid organ/haematopoietic stem cell transplants or systemic lupus erythematosus) or
during primary infection, even (rarely) in those with intact immune systems. Anaemia, haemophagocytic
DIAGNOSIS
syndrome and/or peripheral neuropathy may also result from toxoplasmosis.
Symptomatic disease, aside from congenital toxoplasmosis, is rare without severe immune suppression.
Toxoplasmosis should be highly suspected in any severely immunosuppressed patient with ring-
enhancing brain lesions on computed tomography/magnetic resonance imaging, or in women during
pregnancy with documented seroconversion.
Step-by-step diagnostic approach

The approach to diagnosis will depend on the status of the patient.
Pregnant women
Acute infection during pregnancy is often asymptomatic in women, but when transmitted to the fetus can
have devastating consequences. Antenatal screening for Toxoplasma is not routinely performed in the
US. However, some countries (such as France) do recommend routine testing during pregnancy.
9
Pregnant women with new cervical/occipital lymphadenopathy, or evidence of microcephaly, intracranial
calcifications, hydrocephalus or intrauterine growth retardation in the fetus detected by sonogram, raise
suspicion for acute or recent infection.
In these cases, anti- Toxoplasma IgG and IgM should be checked in the mother. A negative anti-
Toxoplasma IgM rules out acute infection. In rare cases, testing for IgM may have to be repeated if
initially negative and where there is strong clinical suspicion of infection. In areas of high prevalence,
serologies may be checked more than once during pregnancy.
If both IgM and IgG are negative, the mother likely has had no exposure to Toxoplasma gondii . If IgG is
positive and IgM is negative, the mother has a remote history of infection and there is little risk of infection
in the fetus. If anti- Toxoplasma IgM is positive, acute infection cannot be ruled out and more definitive
testing from a Toxoplasma reference laboratory is needed. A positive IgM result is not proof of acute
infection: IgM may persist for up to 1 year after acute infection and there are high rates of false positives
with some testing methods. Toxoplasma -specific IgG avidity index is useful in pregnant women who have
detectable IgG and IgM, in order to identify recent versus chronic infection. It is clear epidemiologically
that new infections are the only ones with significant risk to the fetus; however, the mechanism of IgG
preventing infection in the fetus is not known.
Reference labs have the ability to perform a panel of tests, including the dye test for IgG, IgM enzyme-
linked immunosorbent assay (ELISA), differential agglutination test (AC/HS), IgA ELISA, and IgE
immunosorbent agglutination assay (ISAGA)/ELISA for confirmatory testing. [Toxoplasma Serology
Lab at the Palo Alto Medical Foundation (Palo Alto, CA)] If it is determined that the mother has acute
infection, Toxoplasma polymerase chain reaction (PCR) of amniotic fluid should be performed to
evaluate for transmission to the fetus. Sonogram of the fetus can also be performed to evaluate for
ventricular dilatation, intracranial calcifications, ascites, and hepatomegaly.
Newborn born to a mother with suspected infection during

pregnancy
Congenital disease is often subclinical in the newborn and may mimic other neonatal diseases, making
DIAGNOSIS
its diagnosis more complicated than the diagnosis of acquired infection in adults. In addition, serological
diagnosis is more difficult because maternal IgG passes transplacentally to the fetus.
History and physical examination, including paediatric neurological evaluation and ophthalmological
examination of the retina, should be performed on all newborns at risk for congenital disease in an
attempt to find clinical signs of disease.
Serological evaluation should be performed by an experienced reference laboratory and often includes:
quantitative immunoglobulins, dye test for IgG, IgM ISAGA, IgA ELISA, and IgE ISAGA/ELISA.
Consultation with an infectious diseases consultant is recommended for guidance in interpreting serology
results and in determining a course of treatment for the newborn.
In addition, full blood count with differential, liver function tests including gamma-glutamyl transferase and
bilirubins, cerebrospinal fluid evaluation for cell count, protein, glucose, quantitative IgG and toxo-specific
IgG/IgM, and brain imaging may give clues to the severity of disease.[29]
Interferon-gamma release assay, which measures interferon-gamma production from whole blood
stimulated with T gondii antigen may be used to rule out congenital infection in newborns and thus avoid
the need for serological follow-up. The sensitivity and specificity of the test in infants suspected of having
congenital disease were 94% and 98%, respectively.[30] However, the test is not commercially available
or routinely performed by reference laboratories.
Immunocompromised patients
In a patient who is immunocompromised, whether because of HIV/AIDS, immunosuppressive
medications, or other causes, and who presents with fever and a change in mental status, seizure, or
other focal neurologic deficit with enhancing lesions on computed tomography or magnetic resonance
imaging of the brain, suspicion for toxoplasmosis should be high. If an immunosuppressed patient
presents with fever or malaise and hepatitis, pneumonitis or myocarditis, or with chorioretinitis,
toxoplasmosis should be included in the differential diagnosis. Central nervous system lesions are usually
multiple and are more commonly seen in HIV-infected patients. Transplant recipients may instead present
with cardiac, pulmonary or disseminated disease.
The first test to order in evaluation of toxoplasmosis is serology for anti- Toxoplasma IgG. However,
serologies may be difficult to interpret in the immunocompromised host, because of generally low levels
of immunoglobulins. Toxoplasma PCR can be done on a blood sample, or on other body fluids or tissues
depending on localisation of symptoms. In addition, biopsy of an affected organ (such as cardiac biopsy
in a patient with myocarditis) may reveal the diagnosis.
Enzyme-linked immunosorbent spot assay may be helpful in stratifying risk of recurrence of toxoplasmic
encephalitis in T gondii IgG+ HIV-infected patients.[31] However, it is not used by reference laboratories
because cut-off values to discriminate among patients with adequate or insufficient T gondii -specific
immune responses have not been determined.
[Fig-1]
[Fig-2]
Chorioretinitis
Most cases of toxoplasmic chorioretinitis result from congenital infection that does not become clinically
apparent until after re-activation in the eye. However, outbreaks of acute chorioretinitis associated with
DIAGNOSIS
water contamination have been reported.[32] While the presence of lesions in the fundus should raise
suspicion for toxoplasmosis, proof that Toxoplasma is the cause of such disease is often lacking. Serum
antibody titres are usually low in the presence of active eye lesions caused by congenital disease. In
addition, the appearance of inflammatory lesions is not unique to toxoplasmosis. Similar lesions can be
found with other granulomatous diseases, such as tuberculosis, cat-scratch disease, or toxocariasis,
and, in immunocompromised hosts, cytomegalovirus, herpes simplex virus, or syphilis must also be
considered.
After a full ophthalmological examination reveals evidence of a retinal lesion with associated inflammation,
serology should be checked for evidence of prior infection. In general, if the retinal lesions are
characteristic and serologies are positive, the diagnosis of toxoplasmic chorioretinitis is probable. If the
retinal lesions are atypical and the serologies are positive, diagnosis is less certain.
If the patient is a newborn or infant with congenital disease, typical lesions are bilateral. If the patient is
a child or adolescent with re-activation of congenital disease, active lesions may appear at the periphery
of prior retinal scars, and are usually unilateral. In both cases, anti- Toxoplasma IgG will be present,
although probably at low titres, and IgM is usually absent.
11
If the patient is an adult with acute disease of the eye, active retinal lesions are usually unilateral and IgM
and/or IgG will be positive.
If anti- Toxoplasma IgG and IgM are negative in undiluted serum, chorioretinitis is probably not due
to toxoplasmosis. Demonstration of anti- Toxoplasma antibodies or of Toxoplasma DNA by PCR in
aqueous humor from the anterior chamber of the affected eye can establish a diagnosis in equivocal
cases, but the risks of this procedure often do not outweigh the low risk of a short treatment course, and
clinicians often try a course of treatment.[33]
Risk factors
Strong
immunosuppression
• Immunosuppression (drug-induced, as with antirejection medications for organ donor recipients, and
corticosteroids or immune modulators for autoimmune diseases, or due to immune deficiencies such
as HIV infection) can lead to re-activation of latent infection or symptomatic de novo infection.
• Risk for symptomatic disease in HIV infection increases when the CD4+ T lymphocyte count falls
below 200 cells/microlitre. Patients with CD4 counts <50 cells/microlitre are at greatest risk.[22]
Seropositive patients with a diagnosis of AIDS have a 13% to 47% risk of developing symptomatic
disease without chemoprophylaxis.[23] [24]
• Risk among solid organ transplant recipients is greatest for heart transplants.[25] Risk also exists for
allogeneic stem cell transplant recipients.[26]
• Use of post-transplant prophylaxis with trimethoprim/sulfamethoxazole in both solid organ and
allogeneic stem cell recipients significantly reduces the risk of disseminated toxoplasmosis.
exposure during pregnancy

• Transplacental transmission results only when a seronegative woman acquires toxoplasmosis during
pregnancy. Seropositive women who become pregnant usually do not transmit toxoplasmosis to
DIAGNOSIS
their children unless they are severely immunosuppressed (e.g., because of AIDS or treatments for
systemic lupus erythematosus) and even in those cases transmission is rare. A woman who has a
documented seroconversion should wait at least 6 months before becoming pregnant.[27] Risk of
transmission to the fetus if the mother acquired new infection increases with trimester (9% to 14% risk
in first trimester, 59% to 70% risk in third trimester), but the severity of the manifestations of infection
falls with each trimester.[7] [8] [28]
residence in a high-risk area

• Exposure is more common in warm climates and at lower elevations. Exposure is common in Central
and South America because of water contamination, leading to an increased risk of chorioretinitis,
even in patients with intact immune systems. Exposure is also common in France and some other
European countries, because of ingestion of undercooked infected meat.
ingestion of undercooked or raw meat

• Poses a risk for exposure, not necessarily for symptomatic disease (unless immunosuppressed or
exposed during pregnancy).
exposure to cat faeces
• Poses a risk for exposure, not necessarily for symptomatic disease (unless immunosuppressed or
exposed during pregnancy).
Weak
heavy exposure to soil
• Poses a risk for exposure.
ingestion of unwashed unpeeled raw fruits and vegetables

• Poses a risk for exposure.
occupational exposure
• This could occur with technicians working in a Toxoplasma research lab, or veterinarians. Although
studies show exposure to cat faeces is a risk, studies are not clear as far as cat exposure. Cats
shed oocysts in their faeces during acute infection, and then only intermittently after initial exposure.
Oocysts become infectious only after 1 to 4 days of environmental exposure. Oocysts do not stick to
fur as do some other parasites, and cats' grooming generally removes all oocysts before they become
infective.
History & examination factors

Key diagnostic factors
presence of risk factors (common)
• Key risk factors include immune suppression (drug-induced, HIV infection or other immune
deficiencies), infection during pregnancy, being living in a high-risk area, exposure to cat faeces, and
ingestion of undercooked or raw meat.
chorioretinitis (common)
DIAGNOSIS
• Most cases of toxoplasmic chorioretinitis result from congenital infection that does not become
clinically apparent until after reactivation in the eye. However, outbreaks of acute chorioretinitis
associated with water contamination have been reported.[32]
• While the presence of lesions in the fundus should raise suspicion for toxoplasmosis, proof that
Toxoplasma is the cause of such disease is often lacking.
• Appearance of inflammatory lesions is not unique to toxoplasmosis, and the differential diagnosis
should be considered.
focal neurological deficit (common)

• Seen with encephalitis.
Other diagnostic factors

blurry vision (common)
• Seen with disease of the eye.
slurred speech (common)
13
headache (common)
unsteady gait (common)

confusion (common)
fever (uncommon)
• May be seen with encephalitis or disseminated disease.
lymphadenopathy (uncommon)
• May be seen in symptomatic infection.
fetal microcephaly (uncommon)

• May indicate infection has been transmitted to the fetus.
fetal intracranial calcification (uncommon)

fetal hydrocephalus (uncommon)

fetal intrauterine growth retardation (uncommon)

seizure (uncommon)
DIAGNOSIS
malaise (uncommon)
• May be seen in symptomatic infection; toxoplasmosis should be considered in immunosuppressed
patients.
hepatitis (uncommon)
• May occur in immunosuppressed patients.
pneumonitis (uncommon)
myocarditis (uncommon)
Diagnostic tests
1st test to order
Test Result
anti-Toxoplasma IgG (serum) detectable, with titre
• Can be ordered when screening for previous exposure, such as in
a potential organ transplant recipient, an HIV-infected patient, or a
woman being seen for pre-conception planning.
• Detectable IgG indicates prior infection (in rare cases,
immunocompromised patients with toxoplasmosis can have no
detectable anti- Toxoplasma IgG).
• Titre does not correlate with severity of illness.[6]
anti-Toxoplasma IgM (serum) detectable, with titre
• Can be ordered when evaluating for acute infection.
• A negative test rules out acute infection.
• A positive test does not rule in acute infection. Many commercially
available tests have high false positive rates (up to 60%) and IgM can
remain detectable for many months after initial infection.
• The IgM immunosorbent agglutination assay is available through
reference laboratories for testing of newborns, and is more sensitive
and specific than commercially available tests.[6] Demonstration
of IgM in cord serum or in serum of the newborn is diagnostic of
congenital disease.
• Part of a panel of tests used by reference labs to diagnose infection
during pregnancy and in the newborn. Testing for both IgM and IgA
will identify 75% of congenital infections.[6]
CT (with intravenous contrast) or MR imaging of brain ring-enhancing brain
lesion(s), usually
• Should be ordered for any immunocompromised patient with a
multiple, often involving
decreased level of consciousness or with focal neurological deficits.
the basal ganglia
[Fig-1]
DIAGNOSIS
Other tests to consider
Test Result
anti-Toxoplasma IgA (serum) detectable
• Most helpful for diagnosing congenital disease.
• Demonstration of IgA in cord serum or in serum from the newborn is
diagnostic of congenital disease.
• IgA detection in the adult patient is of little value in diagnosing recent
infection (can remain positive for over a year after acute infection).
• IgA assays are more sensitive than assays for IgM in the diagnosis of
congenital disease. Testing for both IgM and IgA will identify 75% of
congenital infections.[6]
• Part of a panel of tests used by reference labs to diagnose infection
during pregnancy and in the newborn.
15
Test Result
anti-Toxoplasma IgE (serum) detectable
• Part of a panel of tests used by reference laboratories to diagnose
infection during pregnancy or in the newborn.
• Demonstration of IgE in cord serum or in serum from the newborn is
diagnostic of congenital disease.
• High specificity, low sensitivity.
Toxoplasma-specific IgG avidity index (serum) high avidity index
• Useful in pregnant women who have detectable IgG and IgM, in order indicates a mature IgG
response to Toxoplasma
to identify recent versus chronic infection.
• A high avidity result in the first 12 to 16 weeks of pregnancy rules out gondii and presumes
infection is not acute
infection acquired during pregnancy.
• A low IgG avidity result should not be interpreted as an indication of
recent infection because the IgG response can mature slowly over
several months in some people.[34]
differential agglutination test (AC/HS) ratio of AC/HS titre
interpreted as acute
• Used as part of a panel of tests by reference labs to diagnose
infection during pregnancy.
• Uses two antigen preparations found early during acute infection (AC)
and in the later stages of infection (HS)
• Ratios of AC and HS titres are interpreted as acute, equivocal, non-
acute or non-reactive.
• The acute pattern may persist for 1 or more years following infection.
polymerase chain reaction (body fluids and tissue) detection of Toxoplasma
gondii DNA in amniotic
• Perform on amniotic fluid if the mother has serological evidence of
fluid indicates fetal
recent toxoplasmosis, in order to diagnose spread of infection to the
infection. Detection
fetus.
• Diagnostic sensitivity is around 70% and specificity is around 90%.[3] of T gondii DNA in
body fluids in an
• Consider polymerase chain reaction (PCR) of blood, cerebrospinal
fluid (CSF), and urine in newborns with potential congenital disease. immunocompromised
host establishes infection.
• Perform on aqueous or vitreous fluid in patients with atypical retinal
Detection of T gondii in
lesions who have a suboptimal response to anti- Toxoplasma
DIAGNOSIS
vitreous fluid indicates

treatment.[6]
ophthalmic infection.
• In immunocompromised patients suspected to have localised or
disseminated disease, PCR can be performed on blood (buffy coat),
other body fluids, bone marrow aspirate or tissue as a diagnostic aid.
• In patients with AIDS, PCR of CSF has high specificity (97% to
100%) but low sensitivity (50% to 60%). Sensitivity is even lower after
treatment is started.[35]
• Consideration should be given to performing a PCR at regular
intervals for screening purposes in patients who are at high risk of
disseminated disease (e.g., heart or allogeneic haematopoietic stem
cell transplant recipients).[36]
biopsy cysts, free tachy zoites,
inflammatory cells,
• The immunoperoxidase method, which uses antisera to Toxoplasma
necrotising abscesses
gondii , is used on tissue sections, and Wright-Giemsa staining is
used for specimens on slides.
• Biopsy of brain lesions should be performed for patients with
suspected toxoplasmosis who do not have improvement in lesions on
brain imaging after 2 weeks of medical treatment.
[Fig-2]
This is done to rule out other potential causes of such lesions.
Emerging tests
Test Result
IgG or IgM Immunoblot (serum) detectable anti-
Toxoplasma IgG/IgM
• Used in diagnosis of congenital disease.
synthesised by the
• Most useful in newborns with no demonstrable IgM and/or IgA by
neonate indicates
conventional serological methods, born to mothers with confirmed or
congenital infection
highly suspected acute infection.[34]
• Differentiates between maternal IgG transferred through the placenta
and IgG synthesised by the neonate.
• For the newborn, Immunoblot has a sensitivity of around 70%. This
sensitivity increases to 85% within the first 3 months after birth.[3]
enzyme-linked immunosorbent spot assay number of spots
correlates with amount
• Measures interferon-gamma production from a patient’s peripheral
of interferon-gamma
blood mononuclear cells in response to Toxoplasma gondii
production and thus
antigens.[31]
a stronger immune
• May be helpful in stratifying risk of recurrence of toxoplasmic
encephalitis in T gondii IgG+ HIV-infected patients: a higher number response to T gondii
of spots, indicating a greater amount of interferon-gamma production
and thus a stronger immune response to T gondii , may correlate
with reduced risk of recurrence of toxoplasmic encephalitis.
• Not used by reference laboratories because cut-off values to
discriminate among patients with adequate or insufficient T gondii -
specific immune responses have not been determined.
interferon-gamma release assay presence of interferon-
gamma
• Measures interferon-gamma production from whole blood stimulated
with Toxoplasma gondii antigen. Sensitivity and specificity of the
test in infants suspected of having congenital disease were 94% and
98%, respectively.[30]
• Absence of production of interferon-gamma in response to T gondii
antigen may be used to rule out congenital infection in newborns and
thus avoid the need for serological follow-up. Production of interferon-
gamma in response to T gondii antigen may rule in a diagnosis of
DIAGNOSIS
congenital toxoplasmosis.
• Requires only 1 mL of whole blood, which may be an important
consideration in newborn testing. May help to interpret an ambiguous
serological status during pregnancy. Not commercially available or
routinely performed by reference laboratories.
Differential diagnosis
Condition Differentiating signs / Differentiating tests

symptoms
Central nervous system • There may be no difference • Brain biopsy. Usually a
lymphoma in signs and symptoms, solitary lesion.
although fever may be less
common.
Metastatic brain lesions • There may be no difference • Brain biopsy. Evidence of

from primary malignancy in signs and symptoms. malignancy on physical
examination or body
imaging.
17

symptoms
Mycobacterial central • Prior history of residence • Polymerase chain reaction of
nervous system disease in an endemic area. May cerebrospinal fluid (CSF) for
be history of chronic tuberculosis; mycobacterial
cough, weight loss, culture of CSF; brain biopsy
haemoptysis, and other for acid-fast bacilli staining
signs of disseminated and culture; sputum stain
infection. and culture may be positive
for acid-fast bacilli and chest
x-ray may show cavitations
if pulmonary disease also
present.
Aspergillosis • Presence of pulmonary • Cerebrospinal fluid fungal

lesions in addition to central culture; galactomannan.
nervous system lesions
more frequently seen in
aspergillosis. Symptoms may
include cough, chest pain,
and haemoptysis.
Cryptococcosis • Symptoms may include • Cryptococcal antigen from

cough, chest pain, and cerebrospinal fluid (CSF)
haemoptysis. and serum; CSF fungal
culture.
Chagas disease • Prior history of residence in • Demonstration of

an endemic area (Central Trypanosoma cruzi in blood,
and South America). tissue or cerebrospinal fluid;
Acute infection is rarely polymerase chain reaction
symptomatic, but acute of tissue or body fluids;
infection in the very serological tests.
young (<2 years old) may
present with encephalitis
DIAGNOSIS
or focal brain lesions, often

accompanied by myocarditis,
and poses a high mortality
risk. Chronic infections
occasionally develop acute
central nervous system
involvement (encephalitis
with necrotic brain lesions
causing mass effect) in
immunocompromised
patients.

symptoms
Cytomegalovirus • Most common central • Brain CT/MRI/biopsy:
infection nervous system location of lesions are
opportunistic infection in usually near the brainstem or
AIDS patients, presenting periventricular areas.
subacutely with encephalitis, • Polymerase chain reaction
retinitis, progressive of cerebrospinal fluid
myelitis or polyradiculitis. with detectable virus is
In disseminated disease, diagnostic.
may also include liver test • Brain biopsy with + staining
abnormalities or worsening for cytomegalovirus or
renal function. evidence of owl's eyes is
also diagnostic, but is rarely
performed because of the
location of brain lesions.
Herpes simplex infection • Seizures, headache, • Brain CT/MRI/biopsy:

confusion and/or urinary location of lesions is usually
retention can be seen in the medial temporal lobe
disseminated disease, or the orbital surface of the
which usually affects only frontal lobe.
immunocompromised or • Polymerase chain reaction
acute infections in pregnant of cerebrospinal fluid
women; may be associated with detectable virus is
with concurrent genital/oral diagnostic.
lesions; can be spread to
the neonate during acute
infection in the mother, or
via viral shedding in the
birth canal. Neonatal herpes
simplex virus can range from
localised skin infections to
encephalitis, pneumonitis,
and disseminated disease.
DIAGNOSIS
Varicella zoster infection • Multifocal involvement has • Disease is usually a
subacute course, usually vasculopathy, with
only in immunosuppressed, haemorrhage and stroke.
with headache, fever, focal • Polymerase chain reaction
deficits, and seizures. of cerebrospinal fluid
Unifocal involvement is with detectable virus is
more typically seen in diagnostic.
immunocompetent hosts,
occurring after contralateral
cranial nerve herpes zoster,
with mental status changes,
transient ischaemic attacks,
and stroke. Disseminated
varicella zoster virus can
occur in adults during
primary infection, presenting
with pneumonitis and/or
hepatitis.
19

symptoms
Bacterial abscess • May be associated • Cerebrospinal fluid culture or
(including Nocardia spp.) with sinusitis (abutting culture of brain abscess.
the sinuses) or with
bacteraemia. Signs and
symptoms are similar,
including fever and
necrotising brain lesions with
mass effect.
Progressive multifocal • Symptoms are often more • Polymerase chain reaction of

leukoencephalopathy insidious in onset and cerebrospinal fluid for John
progress over months. Cunningham virus.
Symptoms include • Biopsy reveals white
progressive weakness, matter lesions and not well-
poor coordination, and circumscribed lesions.
gradual slowing of mental
function. Only seen in the
immunosuppressed. Rarely
associated with fever or
other systemic symptoms.
DIAGNOSIS
Toxoplasmosis Treatment
Step-by-step treatment approach

Treatment can be divided into treatment of occupational exposure to the organism, primary prophylaxis,
treatment of the active disease, and secondary prophylaxis. Most infections in healthy people are mild and
self-limiting and do not need treatment (other than eye disease).
Treatment regimens for children are generally the same as adults, although doses will differ and some of the
regimens recommended in adults are not necessarily recommended in children due to a lack of evidence.
Consult local paediatric guidelines for further details on the management of children.
Occupational exposure
This group comprises patients exposed to Toxoplasma gondii by contact with infected blood or cell
cultures.
Risk should be stratified on the basis of type of exposure (deep needle stick versus needle prick),
organism burden (highly concentrated versus fluid of low burden) and genotype (virulent type I strain
versus other strain).
Anti- Toxoplasma IgG should be checked immediately to identify those at risk for acute infection.
All seronegative exposed patients or those with unknown serology should be treated. Most experts would
treat all people who have had a definite exposure.
For those with no detectable antibodies, treatment is given for 4 weeks and serology repeated. If
seroconversion is documented, patients should be followed clinically. Patients who are seropositive at
the onset of treatment, or who are known to have been positive before exposure, are probably partially
protected. Most experts would treat high-inoculum deep exposures of a virulent type I strain for 2 weeks.
(Type I strains [RH, GT-1] are commonly used laboratory strains that are highly lethal to mice. These
genotypes have been associated with outbreaks of retinitis and other serious symptomatic disease in
immunocompetent individuals.)
Benefits of treatment include prevention of acute infection. Risks include side effects from medicines.
Women who work in facilities where T gondii is used should have serologies checked at baseline. If
negative, they should avoid exposure once pregnant or once planning to become pregnant.
Of note, there are no published guidelines or trials relating to treatment of occupational exposure.
Prophylaxis in patients with HIV

Prophylactic treatment is given to prevent re-activation of latent disease in immunocompromised
patients.[22] [43]
All HIV+ adults and children older than 6 years of age with CD4+ T lymphocyte counts <100 cells/
microlitre, and all HIV+ children 6 years and younger with CD4% <15%, with detectable anti- Toxoplasma
IgG should receive primary prophylaxis, and counselling on avoidance of future infection (avoidance of
TREATMENT
undercooked meat or contact with cat faeces) should be given to those with no detectable IgG.[22] [43]
First-line prophylaxis is trimethoprim/sulfamethoxazole. This is also the recommended prophylactic

regimen for P jiroveci ( P carinii ) pneumonia. This treatment cannot be used for active disease, as
21
there is a high risk of treatment failure. Toxicities include rash, fever, leukopenia, thrombocytopenia, and
hepatotoxicity.
If a patient is allergic to sulphonamides or shows related toxicity (up to 20% of HIV-positive patients
develop rash with sulfa-based compounds) alternative prophylactic regimens include: atovaquone; daily or
weekly dapsone plus weekly pyrimethamine and calcium folinate; or atovaquone plus pyrimethamine and
calcium folinate.[22]
Primary prophylaxis can be discontinued if the patient is taking antiretroviral therapy (ART) and has
responded with an increase in CD4+ T lymphocyte count to greater than 200 cells/microlitre for 3 or more
months.[22] The safety of discontinuing primary prophylaxis in children with HIV has not been studied.
Prophylaxis in transplant recipients

The routine use of trimethoprim/sulfamethoxazole for post-transplant prophylaxis of Pneumocystis
, regardless of Toxoplasma serostatus, has led to decreased rates of toxoplasmosis in transplant
recipients, and is the most frequently used prophylaxis against toxoplasmosis in transplant recipients.[25]
There are very little data supporting prophylactic regimens, other than trimethoprim/sulfamethoxazole, for
toxoplasmosis in the transplant population. If there is a contraindication to trimethoprim/sulfamethoxazole,
consult an infectious diseases specialist for advice on alternative regimens.[25]
Treatment of active disease in immunocompromised patients

The goal of treatment is to prevent death due to disseminated disease and to prevent/limit damage to
specific organs affected by disease.[22] [43]
Pyrimethamine plus sulfadiazine plus calcium folinate is the treatment of choice. If sulfadiazine sensitivity
develops, clindamycin can be given in its place. Other treatment regimens include trimethoprim/
sulfamethoxazole; atovaquone plus pyrimethamine plus calcium folinate; atovaquone plus sulfadiazine;
or atovaquone alone.[22] These alternative regimens have not been rigorously studied and should not
be used without consultation with an infectious diseases specialist. Adjunctive corticosteroids (e.g.,
dexamethasone, prednisolone) should only be given to treat mass effect or associated oedema, and
should be discontinued as soon as clinically feasible.[22] [43]
Initial treatment duration for all immunocompromised patients is 6 weeks, but duration may be longer if
central nervous system (CNS) lesions have not significantly improved.[22]
In transplant recipients, it is common practice to reduce immunosuppressive therapy whenever

possible and allow treatment to be guided by extensive literature on the treatment of patients with
HIV/AIDS.[25] Treatment failure is suggested by clinical or radiographic worsening (as in the case
of increasing size of brain lesions with encephalitis) after 1 week of therapy or failure to clinically or
radiographically improve after 2 weeks of treatment. If this occurs, a brain biopsy should be performed.
If subsequent brain biopsy confirms toxoplasmic encephalitis, consider changing therapy to one of the
alternative regimens.[22]
After completing initial treatment, patients should continue to receive secondary prophylaxis to prevent re-
TREATMENT
activation of disease for as long as they remain immunocompromised.

[Fig-3]
Pregnant patients with suspected or confirmed acute infection
The goal of treatment is to prevent or limit the severity of infection in the fetus for pregnancies that are
not terminated. While observational cohort studies have shown benefits with treatment, no randomised
controlled trials of antenatal treatment have been performed.[44]
Women infected during the first trimester of pregnancy can be treated with spiramycin to lower the risk of
transmission to the fetus.[45] [46] Chorionic villious sampling can be done by 10 weeks, or amniocentesis
can be done at 15 weeks (with spiramycin continued until results known). Fetal blood sampling can
be done by 17 weeks. If there is no documented infection in the fetus after the first trimester (negative
polymerase chain reaction of amniotic fluid and/or negative IgM from fetal blood sampling), spiramycin
can be continued until delivery.
Spiramycin is estimated to reduce the incidence of vertical transmission by 60%.[6] Of note, spiramycin is
not effective monotherapy if infection has already spread to the fetus.
If transmission has occurred in utero, therapy should be started. Pyrimethamine is effective treatment, but
should be used only after 21 weeks' gestation, as it is a folate antagonist and thus a potential teratogen.
If fetal infection is documented before 20 weeks' gestation, treat with sulfadiazine alone until 20 weeks,
and then add pyrimethamine and calcium folinate. This treatment can be alternated on a monthly basis
with spiramycin, to reduce toxicity to the fetus, or it can be continued until delivery.[29] After 21 weeks'
gestation, treatment consists of sulfadiazine/pyrimethamine plus calcium folinate, alternating with
spiramycin, to maximise efficacy while minimising toxicity.[45]
Full blood counts should be monitored frequently in patients taking pyrimethamine. Calcium folinate dose
can be increased if megaloblastic anaemia, granulocytopenia or thrombocytopenia develops.[29]
Congenital disease
The goal of treatment is to prevent or limit pathology in the CNS and eye. Treatment that is started early
(before 2.5 months of age) and that is continued for 12 months appears to result in more favourable
outcomes, in particular reducing the likelihood of sensorineural hearing loss.[29] [47]
Infected newborns should be treated for 1 year with pyrimethamine plus sulfadiazine plus calcium
folinate.[43] [48] Pyrimethamine dose may need to be decreased and calcium folinate dose may need
to be increased if there is evidence of bone marrow suppression or the inability to tolerate the oral drug
because of excessive gastrointestinal intolerance (nausea, vomiting).
An alternative regimen for those who develop allergy to sulphonamides is pyrimethamine plus calcium
folinate plus clindamycin.[49] However, there are very limited clinical data available to allow for further
recommendations.[29] Additionally, prednisolone may be given with pyrimethamine plus sulfadiazine in
patients with an elevated cerebrospinal fluid (CSF) protein (>10 g/L [1 g/dL]) or when active chorioretinitis
threatens vision. Corticosteroids are continued until resolution of elevated CSF protein or active
chorioretinitis, at which time they should be quickly tapered.
Ophthalmic disease
TREATMENT
The goal of treatment is to limit the amount of damage to the affected area of the eye and to limit the
duration of symptoms. There are few randomised controlled trials pertaining to treatment of toxoplasmic
chorioretinitis. One systematic review concluded that antibiotic treatment probably reduces the risk of
23
recurrent toxoplasmic chorioretinitis, but there was a lack of evidence that antibiotics resulted in better
visual outcomes, and there were no data evaluating the effects of adjunctive corticosteroids.[50] [51]
Despite a lack of evidence to support routine antibiotic treatment, treatment is warranted for severe or
persistent lesions involving the macula or optic nerve, for large retinal lesions with severe inflammation,
and for any lesion in an immunocompromised host.[50] [51] [52] There is some controversy as to whether
to treat small, peripheral retinal lesions in an immunocompetent host.[49]
In immunocompetent patients, both congenital and acquired ocular diseases are treated with
pyrimethamine, sulfadiazine, calcium folinate, and prednisolone.
Corticosteroids are continued until inflammation subsides (usually 1 to 2 weeks) and then quickly tapered.
Pyrimethamine and sulfadiazine should be continued for 1 to 2 weeks after signs and symptoms of active
disease have resolved in an immunocompetent host. Calcium folinate should be continued for 1 week
after cessation of pyrimethamine. There is no confirmed treatment to prevent recurrence of disease,
which can occur in up to 10% of cases, although trimethoprim/sulfamethoxazole has been used for
chronic suppression with some effect.[49] [53] [54]
Immunocompromised patients with isolated ophthalmic disease should receive the above treatment,
followed by chronic suppressive therapy for the duration of their immunosuppression.
[Fig-4]
Prevention of recurrence
Immunosuppressed patients who have completed initial therapy for toxoplasmosis should continue to take
life-long secondary prophylaxis unless immune reconstitution occurs in HIV-infected patients as a result of
ART or immunosuppressive medicines are stopped. Adherence to chronic maintenance therapy is often
difficult for patients, as it is composed of multiple medications with frequent dosing schedules.
The recommended regimen for secondary prophylaxis is pyrimethamine plus sulfadiazine plus calcium
folinate. Trimethoprim/sulfamethoxazole is also an option. Alternative regimens for patients allergic
to sulphonamides include clindamycin plus pyrimethamine plus calcium folinate, atovaquone plus
sulfadiazine, or atovaquone with or without pyrimethamine and calcium folinate.[22]
If immune reconstitution occurs after initiation of ART with sustained CD4+ T lymphocyte counts >200
cells/microlitre for 6 months or greater, one may consider stopping chronic maintenance therapy. The
safety of discontinuing maintenance therapy in children has not been studied.
Treatment details overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Initial ( summary )
TREATMENT
1st prophylactic pyrimethamine +

sulfadia zine + calcium folinate
Initial ( summary )
HIV-positive with CD4+ T lymphocyte
count <100
1st prophylactic trimethoprim/

sulfamethoxa zole
2nd non-sulphonamide prophylactic regimen
seronegative recipients of
seropositive cardiac donors;
seropositive recipients of allogeneic
haematopoietic stem cell transplant

sulfamethoxa zole
Acute ( summary )
newborns: confirmed or highly
suspected congenital disease
1st pyrimethamine + sulfadia zine + calcium

folinate
adjunct prednisolone
2nd non-sulphonamide regimen
non-pregnant adults and children:

confirmed or suspected disease
immunocompromised 1st pyrimethamine + sulfadia zine + calcium

folinate
adjunct dexamethasone
2nd alternative sulphonamide or non-

sulphonamide regimen
immunocompetent 1st observation and assessment
adjunct pyrimethamine + sulfadia zine + calcium

folinate + prednisolone
pregnant: with seroconversion
1st spiramycin OR pyrimethamine +

TREATMENT
Ongoing ( summary )
25
Ongoing ( summary )
immunocompromised: following
symptomatic disease

folinate
2nd alternative maintenance regimen

TREATMENT
Treatment options
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Initial
1st prophylactic pyrimethamine + sulfadia zine

+ calcium folinate
Primary options
» pyrimethamine: adults: 50-75 mg orally

once daily
-and-
» sulfadiazine: adults: 1000 mg orally four
times daily
-and-
» calcium folinate: adults: 10-25 mg orally
once daily
» This group is composed of patients exposed

to Toxoplasma gondii by contact with infected
blood or cell cultures.
» Anti- Toxoplasma IgG should be checked

immediately to identify those at risk for acute
infection.
» All seronegative exposed patients or those

with unknown serology should be treated. Most
experts would treat all individuals with a definite
exposure.
» For those with no detectable antibodies,

treatment is given for 4 weeks and serology
repeated. If seroconversion is documented,
patients should be followed clinically.
» If seropositive at onset of treatment or known

positive prior to exposure, the patient is probably
partially protected. Most experts would treat high
inoculum deep exposures of a virulent type I
strain for 2 weeks.
HIV-positive with CD4+ T lymphocyte
count <100

sulfamethoxa zole
Primary options
TREATMENT
» trimethoprim/sulfamethoxazole: children:
150 mg/square metre of body surface area
orally once daily; adults: 160 mg orally once
daily
27
Initial
Dose refers to trimethoprim component.
Other dose regimens are also recommended
in guidelines as alternative options.
» Given to prevent symptomatic disease.
» For all patients with HIV and CD4+ T

lymphocyte counts <100 cells/microlitre and
children <6 years old with CD4 cell percentage
<15% who have positive serologies.[22] [43]
2nd non-sulphonamide prophylactic regimen
Primary options
» dapsone: children >1 month of age: 2 mg/

kg (or 15 mg/square metre of body surface
area) orally once daily, maximum 25 mg/day;
adults: 50 mg orally once daily
-and-
» pyrimethamine: children >1 month of age:
1 mg/kg (or 15 mg/square metre of body
surface area) orally once daily, maximum 25
mg/day; adults: 50 mg orally once weekly
-and-
» calcium folinate: children >1 month of age:
5 mg orally every three days; adults: 25 mg
orally once weekly
Secondary options
» dapsone: adults: 200 mg orally once weekly

-and-
» pyrimethamine: adults: 75 mg orally once
weekly
-and-
» calcium folinate: adults: 25 mg orally once
weekly
Tertiary options
» atovaquone: children 1-3 months of age

and >24 months of age: 30 mg/kg orally once
daily; children 4-24 months of age: 45 mg/kg
daily
OR
» atovaquone: children 4-24 months of age:

45 mg/kg orally once daily; adults: 1500 mg
orally once daily
-and-
TREATMENT
» pyrimethamine: children 4-24 months of

age: 1 mg/kg (or 15 mg/square metre of body
mg/day; adults: 25 mg orally once daily
-and-
Initial
» calcium folinate: children 4-24 months of
age: 5 mg orally every three days; adults: 10
mg orally once daily
» Second-line options for prophylaxis for HIV-

infected patients who are allergic to, or severely
intolerant of, sulphonamides.[22]
seronegative recipients of
seropositive cardiac donors;
seropositive recipients of allogeneic
haematopoietic stem cell transplant

sulfamethoxa zole
Primary options
consult specialist for guidance on dose;
adults: 160 mg orally three times weekly or
80 mg once daily for 3 months, followed by
160 mg once daily thereafter
» Given to prevent symptomatic disease.
» There are very little data supporting

prophylactic regimens other than trimethoprim/
sulfamethoxazole for toxoplasmosis
in the transplant population. If there
is a contraindication to trimethoprim/
sulfamethoxazole, consult an infectious diseases
specialist for advice on alternative regimens.[25]
Any treatment decisions should be made in
consultation with physicians specialising in
transplantation and infectious diseases.
» After completing initial treatment, patients

should continue to receive secondary
prophylaxis to prevent reactivation of disease,
for as long as they remain immunocompromised.
The optimal duration for prophylaxis after
transplant is not known, and it is sometimes
continued for life.
Acute
newborns: confirmed or highly
suspected congenital disease

TREATMENT
folinate
Primary options
» pyrimethamine: 2 mg/kg orally once daily

for 2 days, followed by 1 mg/kg once daily for
2-6 months, then 1 mg/kg three times weekly
29
Acute
-and-
» sulfadiazine: 50 mg/kg orally twice daily
-and-
» calcium folinate: 10 mg orally/
intramuscularly with each dose of
pyrimethamine
» Given to newborns with confirmed or highly

suspected congenital disease to prevent or limit
damage to the central nervous system and eyes
and to prevent death.
» Initiate before 2.5 months of life and continue

for 1 year.[43] [48]
» Benefits include reduced risk of blindness,

intellectual disability, seizures, and death.
» Risks are side effects from medicines (such

as bone marrow suppression or hypersensitivity
reaction).[29]
Treatment recommended for SOME patients in
selected patient group
Primary options
» prednisolone: 1 mg/kg/day orally
» Given only in the setting of elevated

cerebrospinal fluid (CSF) protein (>1 g) or in
severe, vision-threatening chorioretinitis, when it
is given to prevent loss of vision and blindness,
and to reduce the duration of symptomatic
disease.
» Rapidly taper after resolution of elevated CSF

protein or after resolution of ocular inflammation.
2nd non-sulphonamide regimen
Primary options
» pyrimethamine: 2 mg/kg orally once daily

for 2 days, followed by 1 mg/kg once daily for
2-6 months, then 1 mg/kg three times weekly
-and-
» calcium folinate: 10 mg orally/
intramuscularly with each dose of
pyrimethamine
-and-
» clindamycin: consult specialist for guidance
on dose
TREATMENT
» For patients allergic to or severely intolerant of

sulphonamides.
» None of these alternative regimens

have been adequately studied to warrant
Acute
formal recommendations, although they are
recommended in the guidelines.[29] [43]
Primary options
» prednisolone: 1 mg/kg/day orally
» Given only in the setting of elevated

cerebrospinal fluid (CSF) protein (>1 g) or in
severe, vision-threatening chorioretinitis, when it
is given to prevent loss of vision and blindness,
disease.
» Rapidly taper after resolution of elevated CSF

protein or after resolution of ocular inflammation.
non-pregnant adults and children:
confirmed or suspected disease
immunocompromised 1st pyrimethamine + sulfadia zine + calcium

folinate
Primary options
» pyrimethamine: children: 2 mg/kg

(maximum 50 mg/dose) orally once daily for
3 days, followed by 1 mg/kg (maximum 25
mg/dose) once daily; adults (body weight <60
kg): 200 mg orally as a loading dose, followed
by 50 mg once daily; adults (body weight ≥60
by 75 mg once daily
-and-
» sulfadiazine: children: 25-50 mg/kg
(maximum 1500 mg/dose) orally four times
daily; adults (body weight <60 kg): 1000 mg
orally four times daily; adults (body weight
≥60 kg): 1500 mg orally four times daily
-and-
» calcium folinate: children and adults: 10-25
Can increase dose to 50 mg orally once or
twice daily in adults.
» For all patients with suspected or confirmed

disease. Given to prevent death and organ-
specific damage.
TREATMENT
» Duration of treatment for acute disease is at

least 6 weeks, but patients may require a longer
course if central nervous system lesions have
not resolved.[22] [25]
31
Acute
Primary options
» dexamethasone: children: 1-2 mg/kg

intravenously initially, followed by 1 to 1.5
mg/kg/day given in divided doses every
4-6 hours until symptoms resolve, then
gradually taper; adults: 10 mg intravenously
initially, followed by 4 mg every 6 hours until
symptoms resolve, then gradually taper
» Given only to treat mass effect or associated

oedema. Discontinue as soon as clinically
feasible.
2nd alternative sulphonamide or non-
sulphonamide regimen
Primary options

by 75 mg once daily
-and-
» clindamycin: children: 5 to 7.5 mg/kg
(maximum 600 mg/dose) orally/intravenously
every 6 hours; adults: 600 mg orally/
intravenously every 6 hours
-and-
OR
» trimethoprim/sulfamethoxazole: adults: 5
mg/kg intravenously/orally twice daily
Should be used in place of pyrimethamine
plus sulfadiazine if pyrimethamine is
unavailable or there is a delay in obtaining it.
OR
TREATMENT
» pyrimethamine: adults (body weight <60

Acute
by 75 mg once daily
-and-
» atovaquone: adults: 1500 mg orally twice
daily
-and-
» calcium folinate: adults: 10-25 mg orally
once daily
twice daily.
OR

daily
-and-
» sulfadiazine: adults (body weight <60 kg):
1000 mg orally four times daily; adults (body
weight ≥60 kg): 1500 mg orally four times
daily
OR

daily
» Treatment is given for at least 6 weeks.

Primary options
» dexamethasone: children: 1-2 mg/kg

intravenously initially, followed by 1 to 1.5 mg/
kg/day given in divided doses every 4-6 hours
until symptoms resolve then gradually taper;
adults: 10 mg intravenously initially, followed
by 4 mg every 6 hours until symptoms resolve
then gradually taper
» Given only to treat mass effect or associated

oedema.
immunocompetent 1st observation and assessment
» Most infections in healthy people are mild and

self-limiting and do not need treatment; such
patients should be observed.
adjunct pyrimethamine + sulfadia zine + calcium
TREATMENT
folinate + prednisolone
Primary options
33
Acute
by 75 mg once daily
-and-
» sulfadiazine: children: 25-50 mg/kg
(maximum 1500 mg/dose) orally four times
daily; adults (body weight <60 kg): 1000 mg
orally four times daily; adults (body weight
≥60 kg): 1500 mg orally four times daily
-and-
-and-
» prednisolone: children and adults: 1 mg/
kg/day orally, maximum 40 mg/day, continue
until signs of active, vision-threatening
chorioretinitis subside, then taper and
discontinue
» Immunocompetent patients with chorioretinitis

may require treatment to prevent loss of vision
disease. Treatment for both congenital and
acquired ocular disease is controversial and
depends on expert evaluation of the clinical
findings. It should be undertaken only in
conjunction with an ophthalmologist.
» One systematic review concluded that

antibiotic treatment probably reduces the risk
of recurrent toxoplasmic chorioretinitis, but
there was a lack of evidence that antibiotics
resulted in better visual outcomes, and there
were no data evaluating the effects of adjunctive
corticosteroids.[50] [51] Despite a lack of
evidence to support routine antibiotic treatment,
treatment is warranted for severe or persistent
lesions involving the macula or optic nerve, for
large retinal lesions with severe inflammation,
and for any lesion in an immunocompromised
host.[50] [51] [52]
» Standard treatment is with pyrimethamine,

sulfadiazine, calcium folinate, and prednisolone.
Treatment should be continued for 1 to 2 weeks
TREATMENT
after signs and symptoms resolve.
» Other treatment regimens, such as those

containing clindamycin, trimethoprim/
sulfamethoxazole or azithromycin, have been
used to variable effect, but there is insufficient
Acute
evidence to recommend these treatments.[55]
[56] [57]
pregnant: with seroconversion
1st spiramycin OR pyrimethamine +

Primary options
» spiramycin: 1 g orally every 8 hours
OR
» pyrimethamine: 50 mg orally twice daily for

2 days, followed by 50 mg once daily
-and-
» sulfadiazine: 1000-1500 mg orally four
times daily
-and-
» calcium folinate: 10-25 mg orally once daily
» Given to prevent transmission of infection

to the fetus and to limit severity of congenital
infection.
» Spiramycin can be given before 20 weeks'

gestation and is continued throughout pregnancy
if there is no evidence of transmission of
infection to the fetus. Although marketed
worldwide, it is not currently licensed for
toxoplasmosis in the UK where it can be
obtained on named-patient use.
» If fetal transmission has been documented and

gestation is 20 weeks or greater, spiramycin may
be alternated with pyrimethamine/sulfadiazine/
calcium folinate on a monthly basis (in an
attempt to limit teratogenic exposure for the
fetus), or pyrimethamine/sulfadiazine/calcium
folinate may be given continuously (more
effective treatment of the fetus).[29]
» If fetal transmission is documented before 20

weeks' gestation, give sulfadiazine alone until 20
weeks, and then add pyrimethamine and calcium
folinate.
Ongoing
immunocompromised: following
symptomatic disease
TREATMENT

folinate
Primary options
35
Ongoing
» pyrimethamine: children: 1 mg/kg (or 15
mg/square metre of body surface area) orally
once daily, maximum 25 mg/day; adults:
25-50 mg orally once daily
-and-
» sulfadiazine: children: 42.5 to 60 mg/kg
orally twice daily, maximum 4000 mg/day;
adults: 2000-4000 mg/day orally given in 2-4
divided doses
-and-
» calcium folinate: children: 5 mg orally every
three days; adults: 10-25 mg orally once daily
» Given after initial course of treatment to all

patients to prevent relapse of symptomatic
disease.
» However, it may be stopped in adult HIV-

infected patients on antiretroviral therapy who
have CD4+ T lymphocytes >200 cells/microlitre
for 6 or more months, or in transplant recipients
on no immunosuppressive medications.[22]
2nd alternative maintenance regimen
Primary options
» pyrimethamine: children: 1 mg/kg (or 15

mg/square metre of body surface area) orally
once daily, maximum 25 mg/day; adults:
25-50 mg orally once daily
-and-
» clindamycin: children: 7-10 mg/kg orally
three times daily; adults: 600 mg orally three
times daily
-and-
» calcium folinate: children: 5 mg orally every
three days; adults: 10-25 mg orally once daily
OR
150 mg/square metre of body surface area
or twice daily
OR
» atovaquone: children 4-24 months of age:

45 mg/kg orally once daily; adults: 750-1500
mg orally twice daily
TREATMENT
-and-
» pyrimethamine: children 4-24 months of
age: 1 mg/kg (or 15 mg/square metre of body
mg/day; adults: 25 mg orally once daily
-and-
Ongoing
» calcium folinate: children 4-24 months of
age: 5 mg orally every three days; adults: 10
OR
» atovaquone: children 1-3 months of age

and >24 months of age: 30 mg/kg orally once
daily; children 4-24 months of age: 45 mg/kg
orally once daily; adults: 750-1500 mg orally
twice daily
OR
» atovaquone: adults: 750-1500 mg orally

twice daily
-and-
» sulfadiazine: adults: 2000-4000 mg/day
orally given in 2-4 divided doses
» Alternative regimens given after initial course

of treatment to all patients to prevent relapse of
symptomatic disease.[22]
» However, it may be stopped in adult HIV-

infected patients on antiretroviral therapy who
have CD4+ T lymphocytes >200 cells/microlitre
for 6 or more months, or in transplant recipients
on no immunosuppressive medicines.[22]
TREATMENT
37
Emerging
Intravitreous clindamycin
Clindamycin has activity against Toxoplasma gondii . In patients with disease limited to the eye, local
treatment may be an option. Case series and one randomised controlled trial of patients with chorioretinitis
have shown some benefit with this treatment.[56] [58]
TREATMENT
Toxoplasmosis Follow up
Recommendations
Monitoring
FOLLOW UP
For all patients receiving therapy with pyrimethamine, perform periodic monitoring of blood counts to
detect leukopenia, anaemia, and thrombocytopenia.
For congenitally infected patients, long-term follow-up (beyond completion of 1 year of medical therapy)
should include frequent retinal examinations to evaluate for chorioretinitis.
Children should have repeat audiometric evaluation (at 24-30 months if compliant with recommended
treatment, or annually if untreated/treated otherwise).[61]
HIV-infected patients not taking antiretroviral therapy (ART), as well as those on ART who do not regain
CD4+ T lymphocytes >200 cells/microlitre, and patients who continue to receive immunosuppressive
medications will require life-long suppressive therapy to prevent toxoplasmic encephalitis or disseminated
disease. Medication adherence should be assessed and encouraged by the healthcare provider at every
visit.
Patients with toxoplasmic eye disease should routinely follow-up with an ophthalmologist, as symptomatic
disease is frequently recurrent.
Patient instructions
Patients should be aware that this is a chronic infection.
Seropositive immunosuppressed patients who take trimethoprim/sulfamethoxazole as primary prophylaxis

significantly reduce their risk of developing symptomatic disease.
HIV-infected patients should be informed that taking ART, with a subsequent rise in CD4+ T lymphocytes
>200 cells/microlitre, will protect them from future episodes of symptomatic disease and will allow them to
stop chronic suppressive therapy.
Immunocompetent women infected during pregnancy should know they are not at risk for transmitting
disease during future pregnancies.
Complications
Complications Timeframe Likelihood

pyrimethamine-based bone marrow suppression variable high
Pyrimethamine can suppress the bone marrow. Calcium folinate is given to prevent this toxicity. Calcium
folinate dosing can be increased further to offset effects on bone marrow. If this is ineffective, dosing of
pyrimethamine may have to be decreased.
39
Complications Timeframe Likelihood

sulphonamide rash variable medium
FOLLOW UP
Drug-induced rash can develop at any time during treatment. If rash typical of drug reaction occurs, may
substitute clindamycin or atovaquone for sulfadiazine.
treatment failure variable medium
Early treatment failure may be due to a lack of effect of the prescribed regimen. Late treatment failure is
more likely to be from a patient's poor compliance with taking medications as prescribed. In HIV-infected
patients, early failure may indicate incorrect diagnosis of toxoplasmosis. Brain biopsy should be performed
if not done previously, to confirm the diagnosis, in patients with central nervous system symptoms and
signs. HIV-infected patients also have a high risk of drug intolerance, including rash and hepatitis caused
by the sulfa component.
congenital disease variable medium
While many cases of congenitally acquired infection seem asymptomatic at birth, careful examination
may reveal evidence of eye disease, neurological impairment, hepatosplenomegaly or bone marrow
involvement. Long-term sequelae include impaired vision or blindness, loss of hearing, seizures, palsies,
learning impairment or intellectual disability, hydrocephalus or microcephaly. Children should have
repeat audiometric evaluation (at 24-30 months if compliant with recommended treatment, or annually if
untreated/treated otherwise).[47]
Prognosis
Non-eye infection in immunocompetent patient

Infection is usually mild and prognosis is good without treatment.
Chorioretinitis
Chorioretinitis responds variably to treatment. While patients in whom vision is threatened should receive
treatment, a review of available trials found no benefit of treatment on duration of symptoms or on severity of
disease.[52] Risk for recurrence is high, and treatment of symptomatic episodes does not reduce the risk for
recurrent disease. Thus, frequent ophthalmological follow-up is necessary. In addition, patients may benefit
from chronic suppression with trimethoprim/sulfamethoxazole if they develop frequent recurrences.[52] [59]
Infection in an immunosuppressed patient

Infection is life-long. Thus, if a patient remains immunocompromised he or she remains at risk for
symptomatic disease and should continue to take chronic suppressive therapy. Initiating antiretroviral therapy
in HIV-infected patients with a subsequent rise in CD4+ T lymphocytes to >200 cells/microlitre is the only
means by which chronic suppressive therapy may safely be stopped in these patients.
Infection during pregnancy

Patients may stop treatment after delivery. Women who become infected during pregnancy are often
asymptomatic and will not become symptomatic once treatment is stopped. They are not at risk for
transmission of infection during subsequent pregnancies unless there is underlying immunosuppression.
Antenatal screening and improvement in antenatal diagnosis are associated with a significant reduction in the
rate of congenital infection and better outcome at 3 years of age in children who are infected.[60]
FOLLOW UP
Congenital disease
Many cases are subclinical at birth. More subtle findings (such as changes in IQ), intellectual disability,
seizures, palsies or deafness may develop later in life. In addition, these patients are at risk for developing
chorioretinitis, even into the second decade of life. Thus, congenitally infected children should receive close
follow-up from a paediatric neurologist and an ophthalmologist.[33]
41
Toxoplasmosis Guidelines
Diagnostic guidelines
North America
Guidelines for the prevention and treatment of opportunistic infections in

adults and adolescents with HIV
Published by: Centers for Disease Control and Prevention; National Last published: 2019
Institutes of Health; HIV Medicine Association, Infectious Diseases
Society of America
Guidelines for the prevention and treatment of opportunistic infections

among HIV-exposed and HIV-infected children
Society of America; Pediatric Infectious Diseases Society; American
Academy of Pediatrics
GUIDELINES
Toxoplasma gondii infections

Published by: American Academy of Pediatrics Last published: 2018
Cytomegalovirus, parvovirus B19, varicella zoster, toxoplasmosis in

pregnancy
Published by: American College of Obstetricians and Gynecologists Last published: 2015
(reaffirmed 2017)
Treatment guidelines
Europe
Antenatal care for uncomplicated pregnancies

Published by: National Institute for Health and Care Excellence Last published: 2019
North America
Guidelines for the prevention and treatment of opportunistic infections in

adults and adolescents with HIV
Society of America
Guidelines for the prevention and treatment of opportunistic infections

among HIV-exposed and HIV-infected children
Society of America; Pediatric Infectious Diseases Society; American
Academy of Pediatrics
Toxoplasmosis Guidelines
North America
Toxoplasma gondii infections

Published by: American Academy of Pediatrics Last published: 2018
Cytomegalovirus, parvovirus B19, varicella zoster, toxoplasmosis in

pregnancy
Published by: American College of Obstetricians and Gynecologists Last published: 2015
(reaffirmed 2017)
Parasitic infections in solid organ transplant

Published by: American Society of Transplantation Last published: 2013
GUIDELINES
43
Toxoplasmosis Online resources
Online resources
1. Toxoplasma Serology Lab at the Palo Alto Medical Foundation (Palo Alto, CA) (external link)
ONLINE RESOURCES
Toxoplasmosis References
Key articles
• Desmonts G. Couvreur J. Congenital toxoplasmosis: a prospective study of 378 pregnancies. N Eng J
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Med. 1974 May 16;290(20):1110-6. Abstract
• Department of Health and Human Services, Panel on Opportunistic Infections in HIV-Infected

Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in
HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and
Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious
Diseases Society of America. May 2019 [internet publication]. Full text
• Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons
infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of
America. Clin Infect Dis. 2014 Jan;58(1):e1-34. Full text Abstract
• Department of Health and Human Services, Panel on Opportunistic Infections in HIV-Exposed and
HIV-Infected children. Guidelines for the prevention and treatment of opportunistic infections in HIV-
exposed and HIV-infected children. Feb 2019 [internet publication]. Full text
• McLeod R, Boyer K, Karrison T, et al. Outcome of treatment for congenital toxoplasmosis, 1981-2004:
the National Collaborative Chicago-Based, Congenital Toxoplasmosis Study. Clin Infect Dis. 2006 May
15;42(10):1383-94. Abstract
• Roberts F, Kuo A, Jones L, et al. Ocular toxoplasmosis: clinical features, pathology, pathogenesis,
animal models, and immune responses. In: Ajioka JW, Soldati D, eds. Toxoplasma molecular and
cellular biology. Norfolk, UK: Horizon Bioscience; 2007:chapter 4.
• Pradhan E, Bhandari S, Gilbert RE, et al. Antibiotics versus no treatment for toxoplasma
retinochoroiditis. Cochrane Database Syst Rev. 2016 May 20;(5):CD002218. Full text Abstract
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49. Roberts F, Kuo A, Jones L, et al. Ocular toxoplasmosis: clinical features, pathology, pathogenesis,
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May;56(9):1223-31. Abstract
61. Brown ED, Chau JK, Atashband S, et al. A systematic review of neonatal toxoplasmosis exposure and
sensorineural hearing loss. Int J Pediatr Otorhinolaryngol. 2009;73:707-711. Abstract
49
IMAGES Toxoplasmosis Images
Toxoplasmosis Images
Images
IMAGES
Figure 1: Computed tomography: brain of central nervous system toxoplasmosis

From the collection of Louis M. Weiss, MD, MPH; used with permission
51
Figure 2: Brain pathology: while this is pathology from mouse tissue, it is quite similar to the appearance in
human tissue
From the collection of Louis M. Weiss, MD, MPH; used with permission
Toxoplasmosis Images
IMAGES
Figure 3: Pre- and post-treatment magnetic resonance imaging: brain of central nervous system
toxoplasmosis
From the collection of Rima L. McLeod, MD; used with permission
53
Figure 4: Pre- and post-treatment retinochoroiditis

From the collection of Rima L. McLeod, MD, and published in: Roberts F, McLeod R. Pathogenesis of
toxoplasmic retinochoroiditis. Parasitol Today. 1999 Feb;15(2):51-7; used with permission
Toxoplasmosis Disclaimer
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55
Contributors:
// Authors:
Sarah Hochman, MD
Assistant Professor
Department of Medicine, Division of Infectious Diseases and Immunology, New York University School of
Medicine, New York, NY
DISCLOSURES: SH declares that she has no competing interests.
Kami Kim, MD
Professor of Medicine (Infectious Diseases) and Microbiology and Immunology
Albert Einstein College of Medicine, Bronx, NY
DISCLOSURES: KK is on the advisory board for the Sanford Guide for Antibiotic Therapy.
// Peer Reviewers:
Fabrizio Bruschi, MD
Professor of Parasitology
University of Pisa, School of Medicine, Pisa, Italy
DISCLOSURES: FB declares that he has no competing interests.
Srikrishna Nagri, MD
Gastroenterologist
Dartmouth-Hitchcock Nashua, Nashua, NH
DISCLOSURES: SN declares that he has no competing interests.
George Y. Wu, MD, PhD

Professor of Medicine
University of Connecticut Health Center, Farmington, CT
DISCLOSURES: GYW is on the medical advisory boards of the following: Gilead Sciences, Bristol-Myers
Squibb, AbbVie, and Intercept.

Toxoplasmosis

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Toxoplasmosis

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Toxoplasmosis

The right clinical information, right where it's needed

Last updated: Jul 05, 2019

◊ Symptomatic disease can be seen in immunocompromised patients with re-activation of latent

◊ Symptomatic eye disease can be seen in both immunocompromised and immunocompetent

Disseminated disease: seen in HIV-infected patients, organ transplant recipients, or any

Toxoplasma chorioretinitis: may be seen in congenital disease, immunosuppressed patients, and

Pregnant women and newborns

Atypical presentations include transverse myelitis, polymyositis, myocarditis, pneumonitis or disseminated

Step-by-step diagnostic approach

Newborn born to a mother with suspected infection during

exposure during pregnancy

residence in a high-risk area

ingestion of undercooked or raw meat

ingestion of unwashed unpeeled raw fruits and vegetables

History & examination factors

focal neurological deficit (common)

Other diagnostic factors

slurred speech (common)

unsteady gait (common)

fetal microcephaly (uncommon)

fetal intracranial calcification (uncommon)

fetal hydrocephalus (uncommon)

fetal intrauterine growth retardation (uncommon)

• Seen with encephalitis.

vitreous fluid indicates

This is done to rule out other potential causes of such lesions.

Condition Differentiating signs / Differentiating tests

Metastatic brain lesions • There may be no difference • Brain biopsy. Evidence of

Condition Differentiating signs / Differentiating tests

Aspergillosis • Presence of pulmonary • Cerebrospinal fluid fungal

Cryptococcosis • Symptoms may include • Cryptococcal antigen from

Chagas disease • Prior history of residence in • Demonstration of

or focal brain lesions, often

Condition Differentiating signs / Differentiating tests

Herpes simplex infection • Seizures, headache, • Brain CT/MRI/biopsy:

Condition Differentiating signs / Differentiating tests

Progressive multifocal • Symptoms are often more • Polymerase chain reaction of

Step-by-step treatment approach

Prophylaxis in patients with HIV

First-line prophylaxis is trimethoprim/sulfamethoxazole. This is also the recommended prophylactic

Prophylaxis in transplant recipients

Treatment of active disease in immunocompromised patients

In transplant recipients, it is common practice to reduce immunosuppressive therapy whenever

activation of disease for as long as they remain immunocompromised.

Treatment details overview

1st prophylactic pyrimethamine +

1st prophylactic trimethoprim/

2nd non-sulphonamide prophylactic regimen

1st prophylactic trimethoprim/

1st pyrimethamine + sulfadia zine + calcium

2nd non-sulphonamide regimen

non-pregnant adults and children:

immunocompromised 1st pyrimethamine + sulfadia zine + calcium

2nd alternative sulphonamide or non-

immunocompetent 1st observation and assessment

adjunct pyrimethamine + sulfadia zine + calcium

pregnant: with seroconversion

1st spiramycin OR pyrimethamine +

1st pyrimethamine + sulfadia zine + calcium

2nd alternative maintenance regimen

1st prophylactic pyrimethamine + sulfadia zine

» pyrimethamine: adults: 50-75 mg orally