Referensi Toxo

http://emedicine.medscape.
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Toxoplasmosis
Updated: Dec 17, 2015
Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR; Chief Editor: James G Smirniotopoulos,
MD more...
Overview
Toxoplasmosis is a disease caused by an obligate intracellular protozoal parasite, Toxoplasma
gondii, whose name was derived from the crescent shape of the parasite (toxon is Greek for
"arc"), as well as the name of the North African rodent in which it was first observed,
Ctenodactylus gundi. T gondii is one of the most successful protozoal parasites; it infects the
nucleated cells of virtually all warm-blooded animals. Some species of felines are the
definitive host for sexual reproduction of the parasite; however, asexual reproduction occurs
in secondary hosts, such as rodents, livestock, birds, and humans, culminating in the
formation of tissue cysts, which persist for the lifespan of the secondary host.
Human infection usually occurs via the oral or transplacental route. Consumption of raw or
undercooked meat that contains viable tissue cysts (principally lamb and pork), direct
ingestion of oocysts from contaminated soil and water, and consumption of unwashed
vegetables are common sources of infection. Infection has also been reported in individuals
who drink unpasteurized goat's milk.
Transplacental infection may occur if the mother acquires the parasite acutely or if a latent
infection is reactivated during immunosuppression. Fetal infection usually occurs in the third
trimester, but more severe sequelae may ensue if the fetus is contaminated in the first
trimester.
It is important to differentiate patients with clinical infection from those who are simply
seropositive for T gondii via exposure to toxoplasmosis. In adults, most T gondii infections
are subclinical, but severe infection can occur in patients who are immunocompromised, such
as those who have acquired immunodeficiency syndrome (AIDS) and malignancies. Affected
organs include the gray and white matter of the brain (as shown in the images below), retinas,
[1]
alveolar lining of the lungs (where the infection may mimic Pneumocystis carinii
infection), heart, and skeletal muscle. AIDS-associated Toxoplasma encephalitis results from
reactivation of chronic latent infection in more than 95% of patients.
T1-weighted axial brain magnetic resonance image at the level of the basal ganglia in a 24-year-
old man with human immunodeficiency virus infection. The image shows hypointense lesions in the
region of the thalami (arrows) caused by toxoplasmosis.
View Media Gallery

T1-weighted axial brain magnetic resonance image at the level of the upper lateral ventricles in
a 24-year-old man with human immunodeficiency virus infection (same patient as in the previous
image). The image shows a hypointense mass compressing the right lateral ventricle (arrow) .
Transaxial contrast-enhanced computed tomography scan in a 24-year-old man with human

immunodeficiency virus infection and central nervous system toxoplasmosis (same patient as in the
previous 2 images). This image was obtained after the patient received 20 days of treatment, with
resultant clinical improvement, and shows a low-attenuating mass with minor peripheral ring
enhancement. Note the reduction in the mass effect.
T2-weighted coronal magnetic resonance image at the level of the insulae in a patient with
human immunodeficiency virus infection and central nervous system toxoplasmosis (same patient as
in the previous 3 images). The image shows large, bilateral hyperintense lesions (almost
symmetrically placed on either side of the third ventricle and/or lateral ventricle) (arrows). Note the
slight mass effect on the right lateral ventricle (V).
Congenital toxoplasmosis may be associated with anomalies such as microcephaly,

microphthalmia, hydranencephaly, hydrocephalus secondary to aqueduct stenosis,
porencephalic cyst, and periventricular calcification.
Preferred examination
Magnetic resonance imaging (MRI) is considered superior to computed tomography (CT)

scanning in the detection of brain toxoplasmosis. The administration of intravenous (IV)
contrast material with either modality improves the diagnostic yield and accuracy. However,
ultrasound remains the pillar of intrauterine imaging. [2] Because patients who are
immunocompromised are susceptible to a variety of opportunistic infections and
malignancies, identifying a single cause that is responsible for the patient's symptoms is often
difficult with imaging findings. However, because toxoplasmosis is a treatable condition,
therapy is started immediately, and the scan is repeated in 1-2 weeks. A positive response to
therapy is judged by the regression in size of all lesions.
For excellent patient education resources, visit eMedicineHealth's Brain and Nervous System
Center. Also, see eMedicineHealth's patient education article Brain Infection.
https://radiopaedia.org/articles/neurotoxoplasmosis
Neurotoxoplasmosis
Dr Praveen Jha et al.
Neurotoxoplasmosis, also known as cerebral toxoplasmosis, is an opportunistic infection
caused by the parasite Toxoplasma gondii. It typically affects patients with HIV/AIDS and is
the most common cause of cerebral abscess in these patients 6.
Congenital toxoplasmosis as well as congenital cerebral toxoplasmosis are discussed

separately.
Epidemiology
Toxoplasma gondii is found ubiquitously and antibodies to the organism can be identified in
30% of all humans. The rate varies greatly from population to population and has a wide
reported prevalence: from 6-90% 5. In most cases, the infection is asymptomatic. However, in
immunocompromised patients (especially those with HIV/AIDS), infection can become
established. Cerebral toxoplasmosis is found in 10-34% of autopsies on patients with
HIV/AIDS 5.
The infection most likely occurs once the CD4+ count has dropped below 200 cells/mm 3,6.
Clinical presentation
In immunocompetent patients, acute encephalitis is extremely rare. Even in the

immunocompromised symptoms are typically vague and indolent. Development of new
neurological symptoms in these patients should raise high suspicion of cerebral
toxoplasmosis.
Pathology
Toxoplasma gondii is an intracellular parasite that infects birds and mammals. Its definitive
host is the cat and other Felidae species. Excretion of oocytes in its faecal content followed
by human contaminated uncooked consumption can lead to human infection. In
immunocompetent individuals, it primarily causes a subclinical or asymptomatic infection. In
immunocompromised individuals (e.g. AIDS patients), toxoplasmosis is the most common
cause of a brain abscess.
Pathologically, parenchymal toxoplasma lesions have three distinct zones:
a central avascular zone of coagulative necrosis

an intermediate vascular zone containing numerous organisms
an outermost zone of encysted organisms: Toxoplasma lesions do not have capsule
Radiographic features
Typically cerebral toxoplasmosis manifest as multiple lesions, with a predilection for the
basal ganglia, thalami, and corticomedullary junction 4.
CT
Typically, cerebral toxoplasmosis appears as multiple hypodense regions predominantly in

the basal ganglia and at the corticomedullary junction. However, they may be seen in the
posterior fossa. Size is variable, from less than 1 cm to more than 3 cm, and there may be
associated mass effect.
enhancement: following administration of contrast there is nodular or ring enhancement

which is typically thin and smooth 5
double-dose delayed scan: may show a central filling on delayed scans
calcification: seen in treated cases; may be dot-like or thick and 'chunky'
MRI
T1: may be difficult to identify, but are typically isointense or hypointense 5

T2
o intensity is variable, from hyperintense to isointense 2-5
hyperintense: thought to represent necrotising encephalitis
isointense: thought to represent organising abscess 4
o lesions are surrounded by perilesional oedema
T1 C+ (Gd): lesions often demonstrate ring enhancement or nodular enhancement
MR spectroscopy
o increased lactate 4
o increased lipids
o reduced Cho, Cr and NAA
o increased lipid-lactate peak is characteristic, however, choline peak also may be
seen in few cases
PET/CT scan and thallium SPECT
Minimal or no uptake (cold lesion) as opposed to primary CNS lymphoma 7.
Treatment and prognosis
In general, biopsy is not required and treatment is initiated and follow-up imaging performed.
The exception to this rule are patients who have atypical imaging features (e.g. single lesion)
or who are seronegative for Toxoplasma gondii 6.
Treatment consists of sulfadiazine with pyrimethamine 6.
Differential diagnosis
General imaging differential considerations include:
primary CNS lymphoma: see lymphoma vs toxoplasmosis

cerebral metastases
other infections
o CNS tuberculoma: see CNS tuberculosis
o CNS cryptococcosis
o bacterial abscesses
o neurocysticercosis
References
Article Information
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Cases and Figures
Figure 1: histology showing tachyzoites and encysted bradyzoites
Case 1: CT
Case 2: MRI

Case 3: acute necrotizing toxoplasma encephalitis
Case 4
Case 5
Case 6

Case 7
Case 8: FLAIR
Case 8
Imaging Differential Diagnosis
Primary CNS lymphoma
CNS cryptococcosis
Fungal granulomata
Cerebral metastases
Successful
Treatment of
Cerebral
Toxoplasmosis
with
Clindamycin: A
Case Report
Deepak Madi,1 Basavaprabhu Achappa,1 Satish Rao,1 John T. Ramapuram,1
Soundarya Mahalingam2
DOI 10.5001/omj.2012.100
1
Department of Internal Medicine, Kasturba Medical College, Mangalore, India.
2Departmentof Pediatrics, Kasturba Medical College, Mangalore, India.
Received: 03 May 012

Accepted: 08 July 2012
*Address correspondence and reprints request to: Basavaprabhu Achappa, Department of Internal Medicine, Kasturba Medical College,
Mangalore, India.
E-mail: bachu1504@gmail.com; bachu1504@yahoo.co.in
How to cite this article
Madi D, Achappa B, Rao S, Ramapuram JT, Mahalingam S. Successful Treatment of

Cerebral Toxoplasmosis with Clindamycin: A Case Report. Oman Med J 2012 Sept;
27(5):411-412.
How to cite this URL
Madi D, Achappa B, Rao S, Ramapuram JT, Mahalingam S. Successful Treatment of

Cerebral Toxoplasmosis with Clindamycin: A Case Report.Oman Med J 2012 Sept;
27(5):411-412. Available
from http://www.omjournal.org/fultext_PDF.aspx?DetailsID=292&type=fultext
Abstract
Toxoplasmosis is caused by infection with the obligate intracellular parasite Toxoplasma

gondii. Toxoplasmosis is generally a late complication of HIV infection and usually occurs
in patients with CD4 + T-cell counts below 200/l. Co-trimoxazole (trimethoprim plus
sulfamethoxazole) is the most common drug used in India for the treatment of AIDS-
associated cerebral toxoplasmosis. Other alternative drugs used for the treatment of
cerebral toxoplasmosis are clindamycin plus pyrimethamine and clarithromycin with
pyrimethamine.
A 30-year-old male known case of retroviral disease presented to Kasturba Medical

College, India, with complaints of fever, headache and vomiting. Computed tomography
scan of his brain showed irregular ring enhancing lesion in the right basal ganglia.
Toxoplasma serology revealed raised IgG antibody levels. Based on the CT features and
serology, diagnosis of cerebral toxoplasmosis was made. He was treated with clindamycin
alone as he had historyof sulfonamide allergy. The patient was symptomatically better after
48 hours. After 21 days, repeat CT of brain was done which was normal. The patient
showed good clinical improvement within 48 hours and the lesion resolved completely
within 3 weeks. The authors recommend using clindamycin without pyrimethamine in
resource poor settings and in patients who do not tolerate sulfa drugs.
Keywords: Cerebral toxoplasmosis; Clindamycin; HIV/AIDS.

Introduction
Toxoplasmosis is one of the most common causes of focal brain lesions in patients with
acquired immune deficiency syndrome particularly in developing countries.1 The disease is
treatable, most patients making a full recovery, but it is fatal if untreated. Pyrimethamine
plus sulfadiazine, trimethoprim plus sulfamethoxazole, clindamycin plus pyrimethamine,2
and clarithromycin plus pyrimethamine are used to treat cerebral toxoplasmosis.
Clindamycin plus pyrimethamine is principally used in patients who do not tolerate
sulfonamides. There are limited published data on the use of clindamycin alone in the
treatment of cerebral toxoplasmosis.
Case Report
A 30-year-old male presented to Kasturba Medical College, India, with complaints of

fever, headache and vomiting of 7 days duration. He was diagnosed with retroviral disease
one month back and was on antiretroviral drugs (stavudine, lamivudine, nevirapine). On
examination, he was febrile and drowsy. There was no focal neurological deficit.
Laboratory investigations showed Hb 8.8 g/dL, total white blood cell count 2.2109/L,
ANC 0.8109/L, platelet count 353109/L, ESR 28 mm/1st hour. Peripheral smear showed
dimorphic anemia with leukopenia. Serum electrolytes, blood sugar, renal and liver
function tests were normal. Test for HIV-1 was reactive. His CD4+ count was 38 cells/l.
Chest X-ray and ultrasound of the abdomen were normal.
Computed tomography scan of the brain showed an irregular ring enhancing lesion in the
right basal ganglia with surrounding marked white matter edema and mass effect, (Fig. 1).
CSF analysis was not done (in view of significant edema and mass effect). Toxoplasma
serology revealed raised IgG antibody levels of 326 IU/mL.
Figure 1: Brain CT scan showing irregular ring enhancing lesion in the right basal ganglia
with surrounding marked white matter edema and mass effect.
The patient was treated with IV mannitol, clindamycin (600 mg thrice daily), and
anticonvulsants. Antiretroviral drugs were continued. His symptoms improved gradually
within 48 hours of admission. After 21 days, repeat CT of brain was done which was
normal, (Fig. 2). The patient was discharged from hospital in an ambulatory state. He was
advised to continue antiretroviral drugs and anticonvulsants. Trimethoprim-
sulfamethoxazole was started (prophylactic dose) after following a sulfa desensitization
protocol. He has been asymptomatic for the past 9 months.
Figure 2: CT scan after 21 days of treatment.
Discussion
Human infection occurs via oral or transplacental route. The major clinical features of
cerebral toxoplasmosis are headache, hemiparesis, speech disturbances, cerebellar
dysfunction and cranial nerve palsies.
CT scan typically reveals bilateral, multiple, hypodense ring-enhancing lesions with

surrounding edema in 60% to 70% of patients. Lesions can be solitary in 27% of patients. 3
The patient had a solitary lesion. If the CT scan is normal during initial screening, MRI is
recommended because it is more sensitive and will detect additional lesions in some cases.4
The patient had financial problems so MRI brain was not done. In addition to
toxoplasmosis, the differential diagnoses of single or multiple enhancing mass lesions in
the HIV-infected patient include primary CNS lymphoma, tuberculosis, and fungal or
bacterial abscesses. About 97% of patients with cerebral toxoplasmosis have toxoplasma
IgG antibodies and the levels are usually over 1:256.5 IgG antibody levels in this patient
were 326 IU/mL.
Cerebral toxoplasmosis is generally treated empirically in AIDS patients with compatible

neuro-imaging studies and positive serology. Brain biopsy should only be considered in
patients with negative toxoplasma serology and who do not respond to treatment.6
Trimethoprim/sulfamethoxazole is an alternative treatment for toxoplasma encephalitis

because it is inexpensive and as effective as pyrimethamine-sulfadiazine,7 which is the first
line drug. At our centre, we use trimethoprim/sulfamethoxazole to treat AIDS associated
cerebral toxoplasmosis. Pyrimethamine alone is available only in a few institutions in India
and it was not used in this patient. The patient had a history of sulfa allergy so he was
treated with intravenous clindamycin (600 mg thrice daily) for 3 weeks. Yapar et al.8 have
used clindamycin alone to treat cerebral toxoplasmosis but it took 10 months for complete
radiological clearance of the lesions. While Roemer et al.9 used clindamycin to treat a
patient with cerebral toxoplasmosis but the patient died. The potential use of clindamycin
as a single agent has not been established in randomized clinical trials. The patient in this
case showed good clinical improvement within 48 hours and the lesion resolved completely
within 3 weeks. A positive response to treatment can be demonstrated both clinically and
radiologicaly. Patil et al.10 repeated CT scan after 21 days of treatment to demonstrate
response to antitoxoplasma therapy. Beraud et al.11 used clinical and radiological criteria to
demonstrate response to treatment.
Conclusion
Cerebral toxoplasmosis can be treated with clindamycin without pyrimethamine in resource

poor settings countries and in patients who do not tolerate sulfa drugs.
Acknowledgements
The authors reported no conflict of interest and no funding was received in this work.
References
1. Shankar SK, Mahadevan A, Satishchandra P, Kumar RU, Yasha TC, Santosh V, et al. Neuropathology of
HIV/AIDS with an overview of the Indian scene. Indian J Med Res 2005 Apr;121(4):468-488.
2. Dannemann B, McCutchan JA, Israelski D, Antoniskis D, Leport C, Luft B, et al; The California
Collaborative Treatment Group. Treatment of toxoplasmic encephalitis in patients with AIDS. A randomized
trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. Ann Intern Med 1992
Jan;116(1):33-43.
3. Porter SB, Sande MA. Toxoplasmosis of the central nervous system in the acquired immunodeficiency
syndrome. N Engl J Med 1992 Dec;327(23):1643-1648.
4. Ciricillo SF, Rosenblum ML. Use of CT and MR imaging to distinguish intracranial lesions and to define
the need for biopsy in AIDS patients. J Neurosurg 1990 Nov;73(5):720-724.
5. Skiest DJ, Erdman W, Chang WE, Oz OK, Ware A, Fleckenstein J. SPECT thallium-201 combined with
Toxoplasma serology for the presumptive diagnosis of focal central nervous system mass lesions in patients
with AIDS. J Infect 2000 May;40(3):274-281.
6. Mathews C, Barba D, Fullerton SC. Early biopsy versus empiric treatment with delayed biopsy of non-
responders in suspected HIV-associated cerebral toxoplasmosis: a decision analysis. AIDS 1995
Nov;9(11):1243-1250.
7. Torre D, Speranza F, Martegani R, Zeroli C, Banfi M, Airoldi M. A retrospective study of treatment of

cerebral toxoplasmosis in AIDS patients with trimethoprimsulphamethoxazole. J Infect 1998;17:15-18 .
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alone in an HIV-positive patient allergic to sulfonamides. Int J Infect Dis 2005 Jan;9(1):64-66.
9. Roemer E, Blau IW, Basara N, Kiehl MG, Bischoff M, Gnzelmann S, et al. Toxoplasmosis, a severe
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Apr;80(4):583-587.
The Center for Food Security & Public Health: Toxoplasmosis. May 2005.
Toxoplasmosis
By Samantha Yager
Disease Etiology/History:
Toxoplasmosis is caused by the food borne protozoan parasite Toxoplasma gondii. [1]
Nicolle and Manceaux first observed T. gondii in rodents in 1908, and it
was identified as an agent of infectious disease in 1932 when it was discovered in a
congenitally infected infant. It wasnt until 1968 that it was considered a potentially
fatal disease in adults due to several cases of toxoplasma encephalitis found in
hematologic cancer patients. [2]
Transmission:
There are three main routes of transmission that infect people with toxoplasmosis.
1. Toxoplasmosis is transmitted to humans by way of the tissue form of T. gondii through

eating under cooked, contaminated meat or other food products that may have been cross
contaminated.
2. Infected cats can pass the oocyst form of T. gondii in their feces, which can be accidently
ingested by humans.
3. Toxoplasmosis can be passed from mother to unborn child during pregnancy. This normally
occurs only if the mother is newly infected or becomes infected while pregnant. [3]
In rare cases people may become infected from an organ transplant, blood transfusion, or unsafe
handling of infected blood.
Reservoirs:
The only definitive hosts and main reservoirs of T. gondii are cats and other members of the
feline family. [4] Birds and rodents are intermediate hosts for T. gondii, they become infected by
ingesting soil, water or plants that are contaminated with the parasite oocysts. Humans, animals
bred for human consumption and wild game may also be reservoirs for T. gondii. [5]
Specific Microbial Characteristics:
T. gondii is a single celled protest, has no flagella, an amoeboid-like body and is classified as
an apicomplexan within the group alveolate. [7] There are three forms of T. gondii which include
oocysts, tachyzoites and brodyzoites. Felines produce oocysts and pass them in their feces, humans
or other animals ingest the oocysts and they develop into tachyzoites which then form tissue cysts
called brodyzoites once they localize in the muscle tissue or central nervous system. [6] The tissue
form of T. gondii can be viewed under a microscope and appear as bananas or crescent shapes.
Specific Tests for Identification:
Serologic testing, which measures immunoglobulin G (IgG), is used to diagnose

toxoplasmosis. Immunoglobulin M (IgM) may be measured to determine the length of time a person
has been infected; this is especially important if the person is pregnant or immunocompromised. [8]
Dye test (DT), indirect fluorescent antibody test (IFA) and enzyme immunoassays
(ELISA,Immunoblots) are tests used to detect these antibodies. [15] Other means of testing such as
observing the parasite in stained tissue sections, cerebrospinal fluid or other biopsy material,
isolating the parasite from body fluids or blood and testing amniotic fluid for T. gondii may also be
used to determine a diagnosis. [8] Toxoplasmosis is often difficult to diagnose due to the signs and
symptoms being similar to common illnesses such as the flu or mononucleosis.
Signs and Symptoms:
The incubation period for toxoplasmosis is 1-3 weeks. Most people with healthy immune
systems show no or mild symptoms of toxoplasmosis such as: enlarged lymph nodes in the head and
neck, headache, fever, muscle pain and sore throat. T. gondii remains inactive inside the body once a
person has been infected and may become reactivated if they become immunosuppressed. [9] In
those with compromised immune systems symptoms may include confusion, fever, headache,
blurred vision and seizures. [1] Pregnant women may miscarry, have a still birth or give birth to a
child with signs of toxoplasmosis. Infants born with toxoplasmosis may show no symptoms at birth
but may develop vision loss, mental disability, and seizures later in life. [9]
Virulence Factors:
T. gondii infects between 20-60% of the worlds population. It is capable of living inside
all warm-blooded animals, including humans. T. gondii can enter a host cell by phagocytosis over a
period of 2-4 minutes or by actively invading the host cell very rapidly, within 25-40 seconds. [10] As
a member of the apicomplexans, it uses an actin-based motility to directly penetrate its host cell. T.
gondii goes into a vacuole, once inside the host cell, which resists fusion with endosomes and
lysosomes. This vacuole also allows the parasite to obtain nutrients it needs to rapidly replicate and
consume the host cell. [12] Transmission of T. gondii may be enhanced due to the parasite altering
host behavior. It is still unknown as to exactly how the parasite modifies host behavior, but studies
have shown a correlation between T. gondii infection and reduced fear or increased attraction
toward the parasite. [11]
Prevention and Treatment:
Healthy individuals can lower their chance of infection by cooking foods to proper
temperatures, freezing meats for several days before cooking, peeling or washing fruits and
vegetables thoroughly before eating, avoiding cross contamination, not drinking untreated water,
using precaution when near any area cat feces may be present and always washing hands properly.
People who are immunocompromised should follow all of the same precautions as well as taking
preventive medications. [13] There is currently no vaccine for toxoplasmosis.
Treatment for people who are showing signs and symptoms of acute toxoplasmosis, but are
otherwise healthy, include a malaria medication called pyrimethamine (Daraprim) along with folic
acid and the antibiotic sulfadiazine. In people with HIV/AIDS treatment is normally the same but the
medications may need to be taken for the remainder of their life. Pyrimethamine, folic acid, and
clindamycin (Cleocin) may be used as an alternative treatment in people with HIV/AIDS. In infected
pregnant women whose baby is not infected the antibiotic spiramycin may be used. In extreme
cases, an unborn child may be treated with pyrimethamine and sulfadiazine. [14]
Local Cases/Outbreaks:
About 225,000 cases of toxoplasmosis are reported each year, with 500 people being
hospitalized and 750 resulting in death making toxoplasmosis the 3rd most common casus of death
from food borne disease in the United States. [22] The prevalence of T. gondii in the United States
declined from 14.1% to 9% from 1999-2004, as compared to the previous ten years. [19] Ocular
toxoplasmosis is the most common infection of the retina in the United States. Every year 1,075,242
people are infected with T. gondii of the retina. [20] Two rare cases of pituitary adenoma associated
with T. gondii have been reported. The cases involved a 43 and 19 year old woman both presenting
with headaches, weakened eye sight and no damage to the brain other than the pituitary gland. T.
gondii cysts were found in both tumors. [21]
Global Cases/Outbreaks:
Toxoplasmosis infections occur in all parts of the world, especially in warm, humid climates.
According to world wide serological surveys, 3-80% of healthy adults have been exposed to T. gondii
and 80-90% of healthy individuals are asymptomatic. [17] The Greater Victorian Area of British
Columbia, Canada identified 110 cases of acute Toxoplasma gondii infections between January 1,
1195 and September 6, 1995. The infections were linked to municipal drinking water and included 42
pregnant women, 11 newborns and 57 non-pregnant individuals. This outbreak was the largest ever
reported at this time. [16] A similar case was reported occurring in Santa Isabel do Ivai, Brazil in
November 2001. A physician found two people with positive results for IgM and IgG, which led to
further investigation. From November 2001 through January 2002, 294 more cases of toxoplasmosis
were reported in the area. [18]
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http://www.foodsafety.gov/poisoning/causes/parasites/toxoplasmosis/index.html 03/01/14
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http://www.mayoclinic.org/diseases-conditions/toxoplasmosis/basics/treatment/con-20025859
03/07/14
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Municipal Drinking Water-British Colombia. September 30, 1995.
ftp://ftp.cdc.gov/pub/publications/mmwr/International/e-2118.pdf 03/07/14
[17] The Center for Food Security and Public Health. Toxoplasmosis. May 2005.
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[18] Emerging Infectious Disease:Center for Disease Control. Waterborne toxoplasmosis, Brazil,
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1115.pdf 03/08/14
[19] Jeffrey L. Jones, Deanna Kruszon-Moran, Kolby Sanders-Lewis, and Marianna Wilson.
Toxoplasma gondii infection in the United States, 1999-2004, Decline from the Prior
Decade. April 10, 2007. http://www.ajtmh.org/content/77/3/405.long 03/08/14
[20] The American Journal of Tropical Medicine and Hygiene. Annual Burden of Ocular
Toxoplasmosis in the United States. March 2010.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829910/ 03/08/14
[21] Journal of Clinical Pathology. Two Case Reports of Pituitary Adenoma Associated with
Toxoplasma gondii Infection. December 2002.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769814/ 03/08/14
Jose G. Montoya.The Journal of Infectious Diseases.Laboratory Diagnosis of Toxoplasma
gondii Infection and Toxoplasmosis, Stanford University School of Medicine, Stanford
California. 2002.
Laboratory Diagnosis of Congenital

Toxoplasmosis
1. Christelle Pomaresa,b,c,d and
2. Jose G. Montoyaa,b
a
1. Palo Alto Medical Foundation Toxoplasma Serology Laboratory, National Reference
Center for the Study and Diagnosis of Toxoplasmosis, Palo Alto, California, USA
2. bStanford University, Division of Infectious Diseases, Stanford, California, USA
3. cINSERM U1065, Centre Mditerranen de Mdecine Molculaire, Toxines
Microbiennes dans la Relation Hte-Pathognes, Nice, France
4. dService de Parasitologie-Mycologie, Centre Hospitalier Universitaire de Nice, Nice,
France
1. C. S. Kraft, Editor
+ Author Affiliations
1. Emory University
Next Section
ABSTRACT
Recent studies have demonstrated that screening and treatment for toxoplasmosis during
gestation result in a decrease of vertical transmission and clinical sequelae. Early treatment
was associated with improved outcomes. Thus, laboratory methods should aim for early
identification of infants with congenital toxoplasmosis (CT). Diagnostic approaches should
include, at least, detection of Toxoplasma IgG, IgM, and IgA and a comprehensive review of
maternal history, including the gestational age at which the mother was infected and
treatment. Here, we review laboratory methods for the diagnosis of CT, with emphasis on
serological tools. A diagnostic algorithm that takes into account maternal history is presented.
Previous SectionNext Section
INTRODUCTION
In 1939, Wolf et al. (1) reported for the first time that the intracellular protozoan parasite
Toxoplasma gondii was a pathogen for humans and that it was capable of causing congenital
disease as well (1, 2). Following this major discovery, it was promptly recognized that the
clinical spectrum of fetuses, newborns, and children congenitally infected with T. gondii
could range widely from complete apparent normality to severe neurological and ocular
disease and even death (3). It is now well accepted that congenital toxoplasmosis (CT) has a
worldwide distribution; recently, the global annual incidence of CT was estimated to be
190,000 cases (95% confidence interval [CI], 179,000 to 206,300), translating into an
enormous disease burden of 1.20 million disability-adjusted life years (DALYs) (95% CI,
0.76 to 1.90) per annum (4). However, the morbidity and mortality associated with this
disease is preventable, treatable, and reversible (3).
Effective anti-Toxoplasma treatment, when instituted as early as in utero during the

gestational period, has been shown to significantly decrease mother to child transmission as
well as to improve clinical outcomes (510). Thus, it is imperative that laboratory tests
employed for the diagnosis of CT be sensitive, specific, and exhibit high predictive values in
order to promptly identify fetuses and newborns that are likely to significantly benefit from
treatment interventions. Here, we review serological tests that are currently available to
clinicians for the diagnosis of CT. Additional methods, such PCR, histological stains,
isolation of the parasite in mice, and brain imaging studies, and other general laboratory
abnormalities associated with the disease are mentioned but are not reviewed in detail since
they are beyond the scope of this review. In addition, the relevance of maternal history (e.g.,
gestational age at which the mother was infected and whether the mother received anti-
Toxoplasma treatment or not) is incorporated in a diagnostic algorithm.
GENERAL CONSIDERATIONS
Congenital toxoplasmosis can occur when a woman acquires T. gondii infection for the first
time during pregnancy or, more rarely, shortly before conception. Infection of the fetus
occurs when the parasite crosses the hemato-placental barrier and reaches the fetus. The risk
of transmission essentially varies with gestational age and whether the mother receives
treatment or not (510). The overall risk of transmission in mothers who have been treated
during gestation is around 30%. However, it varies significantly with the gestational age at
which the treated mother acquired the infection, from 15% at 13 weeks, 44% at 26 weeks,
and 71% at 36 weeks (10, 11). Less frequently, CT can also occur when women infected in
the distant past and prior to gestation reactivate their latent infection due to significant
immunosuppression.
The diagnosis of CT can be confirmed or excluded more accurately when comprehensive

clinical and laboratory information on the mother and her offspring is readily available to
treating physicians. This information significantly affects the interpretation and pretest
probability of different laboratory tests (12, 13).
Ideally, it should be established first whether the mother is immunocompromised or

immunocompetent and whether she belongs to one of the following three groups: (i) never
infected with Toxoplasma and confirmed to remain seronegative 1 month after birth (no risk
for CT), (ii) chronically infectedmother acquired her infection prior to gestation (no risk
for CT unless she is immunocompromised), or (iii) acutely infectedmother acquired her
infection during gestation or within 3 months prior to gestation (at risk for CT). For group 3,
it is important to establish (or estimate) the month during gestation at which maternal
infection was acquired and whether the mother received anti-Toxoplasma treatment (and if
so, which drugs) since the sensitivity and interpretation of laboratory tests can be largely
affected by these variables (14). For instance, the sensitivity of serological test results in
newborns is lower in those born to mothers who acquired their infection early in gestation
and/or received anti-toxoplasmosis treatment during gestation than it is in those born to
mothers who acquired their infection late in gestation and/or did not receive treatment (14).
Information on the presence of clinical signs in the fetus and newborn may also be helpful in
the interpretation and recommendations, for instance, regarding intervals for follow-up
testing after birth or indication for additional tests (e.g., Toxoplasma PCR).
PRINCIPLES AND METHODS AVAILABLE FOR THE

DIAGNOSIS OF CONGENITAL TOXOPLASMOSIS
Several methods have been used for decades for the diagnosis of CT, including detection of
Toxoplasma-specific humoral immune responses, amplification of Toxoplasma DNA,
identification of Toxoplasma-specific antigen in tissues, and isolation of the parasite (Table
1) (1517).
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TABLE 1
Principles and methods used for the diagnosis of congenital toxoplasmosis
Diagnosis of CT in the fetus.During gestation, the presence of the parasite in amniotic fluid
(DNA amplification, microscopy, or isolation of the organism) and/or fetal tissues (DNA
amplification, antigen staining, microscopy, or isolation of the organism) is diagnostic of CT
(Table 1). The most commonly used and accepted laboratory method for the diagnosis of CT
during gestation is the use of PCR in amniotic fluid, and a positive test result is diagnostic of
CT.
Diagnosis of CT in newborns and infants.In the postnatal period, the gold standard to
establish a diagnosis of CT is the persistence of Toxoplasma IgG by 12 months of age.
Conversely, the standard to rule out the diagnosis is the decrease of Toxoplasma IgG titers
until its disappearance at 12 months of age in the absence of treatment (Fig. 1).
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FIG 1
Congenital toxoplasmosis diagnostic algorithm for testing and monitoring infants according
to whether maternal antenatal screening and treatment was performed (a) or not (b). Cases in
gray and white represent data and/or action before and after birth, respectively.
In the absence of comprehensive clinical history and previous Toxoplasma laboratory test
results, diagnosis of CT after the first year of life is confounded by the possibility of the child
acquiring infection in the postnatal period. For this reason, all reasonable efforts should be
undertaken to diagnose or exclude CT during gestation or the first year of life (infant period).
The most common laboratory method utilized worldwide for the diagnosis of CT in newborns
and infants is serological detection of various isotypes of Toxoplasma antibodies in
peripheral blood (serum). Although laboratories vary on the choice of specific method to
detect Toxoplasma-specific antibodies, Toxoplasma IgG, IgM, and IgA should always be
tested since having a combination of IgM and IgA test results, in addition to IgG, has greater
sensitivity than either test alone (13, 1518).
Toxoplasma PCR testing in cerebrospinal fluid (CSF), peripheral blood, and urine can be
another laboratory tool that can be used for the early diagnosis of CT and is particularly
helpful in regions where antenatal screening and treatment programs have not been
implemented (19).
For Toxoplasma IgG detection, the dye test is the reference method and remains the gold
standard. However, the dye test can only be performed in reference laboratories due to its
dependence on the use of live parasites. Other methods that are more commonly used rely on
enzyme-linked immunosorbent assay (ELISA) and ELISA-like assays, agglutination, and
indirect immunofluorescence. Many ELISA and ELISA-like assays used for the detection of
both Toxoplasma IgG and IgM use automated and closed systems that also allow sequential
testing for the detection of IgG and IgM antibodies against other pathogens (17).
For Toxoplasma IgM detection, in addition to the same methods used for Toxoplasma IgG,
the IgM immunosorbent agglutination assay (ISAGA) is used and is known for its overall
higher sensitivity compared to ELISA and ELISA-like assays (e.g., 81.1% versus 64.8%)
(20). The IgM ISAGA is considered to be the method of choice for the detection of
Toxoplasma IgM in infants younger than 6 months of age (Table 2).
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TABLE 2
Overview of sensitivity and specificity of Toxoplasma serological tests in the neonatal period
For Toxoplasma IgA detection, ELISAs are mostly available. However, IgA ISAGAs are also
performed in a few laboratories (20, 21).
Although the use of Toxoplasma IgE was initially reported as promising in some studies, it
became subsequently obvious that it did not have any value to the combinatorial power of
IgM and IgA (22, 23).
During the postnatal period, the detection of Toxoplasma IgG is confounded by the fact that
maternal IgG has been passively transferred across the placenta to the neonate. In addition,
the detection of Toxoplasma IgM and IgA in the neonate can also be contaminated with some
maternal Toxoplasma IgM during the first 5 days of life and with maternal Toxoplasma IgA
during the first 10 days of life. To overcome this challenge, methods to compare maternal and
infant IgG, IgM, and IgA profiles have been developed, such as Western blotting. Western
blots depict several bands that represent the binding between patient IgG, IgM, or IgA against
various known Toxoplasma-specific antigens. The principle is to compare these bands
between serum samples from the mother and infant to detect, in cases of congenital
toxoplasmosis, autonomous synthesis of antibodies in the infant's serum. This can be
established by the presence of bands that are not present in the mother's serum or by bands
that have greater intensity in the infant's serum than in the mother's serum. Western blotting
has been shown to establish diagnosis up to 3 months earlier than conventional serological
methods (24). The sensitivity of Western blotting in combination with conventional
serological methods has been shown to be superior to Western blotting or conventional
methods used alone. However, the interpretation of Western blots may be difficult and should
not be performed after a certain age due to false-positive test results (e.g., for some kits, false-
positive results are seen with Toxoplasma IgG and IgM Western blotting after 1 and 3
months of life, respectively) (17, 25, 26).
Most nonreference laboratories can perform the Toxoplasma IgG, IgM, and PCR tests.
However, tests such as the IgM ISAGA, Western blotting, and isolation are only performed
in reference laboratories and have been validated in infants. In combination with results from
conventional tests, they yield a sensitivity that is greater than the sensitivity of each test alone
(20, 23).
Few other methods have been described for the diagnosis of congenital toxoplasmosis. The
enzyme-linked immunofiltration assay (ELIFA) is an alternative method to compare the
immunological profile between mother and infant, but it is performed only in very few
laboratories (20). The interferon gamma released after T-cell stimulation by T. gondii
antigens has be proven to be useful for the diagnosis of congenital toxoplasmosis, but it is
currently not commercially available (27). Detection and follow-up of Toxoplasma IgG in
oral fluid have also been used to monitor infants with suspected congenital toxoplasmosis,
and it is a promising diagnostic tool (28). In addition, brain imaging studies and retinal exams
can also exhibit findings that are highly suggestive of the disease, and in the absence of
alternative etiologies and proper clinical context, they can be diagnostic (Table 1).
OVERALL DIAGNOSTIC APPROACH

Congenital toxoplasmosis can be diagnosed during gestation and/or after birth in the postnatal
period. The diagnostic approach to newborns and infants varies significantly depending on
whether the mother was screened and treated during gestation and whether a diagnosis of
fetal infection was attempted by amniocentesis. Routine prenatal screening and treatment
programs have only been implemented in a few countries (Austria, Belgium, France, Norway,
Uruguay, and some regions in Italy and Brazil). The clinicians managing newborns born in
these regions benefit from having available information, such as maternal serological and
amniotic fluid PCR test results, precise gestational age at which the mother was infected, and
detailed anti-Toxoplasma treatment history.
In contrast, the vast majority of newborns worldwide, including those in the United States,
are born in regions where such programs have not been implemented (23). The absence of or
incomplete prenatal screening and treatment has been identified as an important risk factor
for congenital toxoplasmosis (29).
DIFFERENCES IN THE DIAGNOSTIC APPROACH

TO CT ACCORDING TO THE PRESENCE OR
ABSENCE OF MATERNAL SCREENING AND
TREATMENT PROGRAMS
Some important differences are observed in the approach, performance, and utilization of
laboratory methods for the diagnoses of CT between regions with Toxoplasma screening and
treatment programs during gestation and those without (Fig. 1). The main objective of
Toxoplasma maternal screening programs is to diagnose the acute infection during gestation
as early as possible. Women who are at risk (Toxoplasma seronegative) are identified during
their first prenatal visit and followed at intervals that vary with the program (3). This
approach allows for the prompt initiation of treatment of the mothers who seroconvert and of
fetuses that become infected. This strategy has been shown to decrease mother to child
transmission and severe disease and death in the offspring (9). As a result, fetuses and infants
in these regions are diagnosed and treated much earlier than in regions where these programs
have not been implemented. An unintended consequence of the screening/treatment approach
is that laboratory methods, such as serological and PCR tests, are less sensitive in these
regions (12, 23). However, pediatricians and clinicians managing these newborns have
immediate access to maternal information and serum, which are critical to the choice of
laboratory methods for the diagnosis of CT. For instance, they have available information
that is known to influence the choice and performance of laboratory tests, such as precise
knowledge about the gestational age at which the mother was infected and whether anti-
Toxoplasma treatment was received and, if so, what regimen.
In regions where screening programs are not implemented, critical information on the mother
is usually not available. This lack of information often leads to unnecessary laboratory testing
in infants who were not at risk of being infected and are later confirmed to be uninfected. In
addition, treatment is delayed in newborns that are in fact infected (23). The absence of
maternal treatment in regions without screening programs may explain why PCR is more
commonly utilized for neonatal diagnosis in these regions since higher sensitivity in PCR
assays is expected and has been observed (19, 23).
SIMILARITIES IN THE DIAGNOSTIC APPROACH

TO CT ACCORDING TO THE PRESENCE OR
ABSENCE OF MATERNAL SCREENING AND
TREATMENT PROGRAMS
The serological approach to the diagnosis of CT in regions with or without these programs is
similar once it has been established that the newborn belongs to one of the following three
categories (Fig. 1): (i) CT is not likely because mother and newborn are Toxoplasma
seronegative, (ii) CT is not likely because the mother is chronically infected (the risk of CT is
only present in newborns whose mothers are significantly immunocompromised), or (iii) CT
is likely since mother was infected (or is suspected to have been infected) during gestation
and/or newborn has clinical signs at birth. Mothers who are Toxoplasma seronegative during
gestation and are confirmed to be so 1 month after birth are not at risk for CT. Therefore,
serological follow-up in their newborns is not required. The reason to confirm the
seronegative status of the mother 1 month after birth is to rule out the rare possibility that the
mother may have been infected shortly before delivery.
Mothers who have been confirmed of having acquired the infection in the distant past and
prior to pregnancy are not at risk of CT unless the mother is actively immunosuppressed
during gestation (e.g., a mother with AIDS who reactivates her Toxoplasma infection or her
CD4 count is below 200 cells/mm3). Newborns born to these mothers will have detectable
Toxoplasma IgG transferred passively from the mother and do not require serological follow-
up. However, in regions where maternal screening programs have not been implemented,
certainty that the mother has been infected in the distant past and prior to gestation is often
impossible. Frequently, the first serum available is obtained in the second trimester or later or
at birth. In these situations, when the serological test results exhibit a positive Toxoplasma
IgG and IgM, only reference laboratories, such as the Palo Alto Medical Foundation
Toxoplasma Serology Laboratory (PAMF-TSL; http://www.pamf.org/Serology/), have
serological assayse.g., IgG dye test, IgM ELISA, Avidity, differential agglutination
(acetone [AC]-fixed versus formalin [HS]-fixed tachyzoites) test (AC/HS test), and IgA and
IgE ELISAsthat can attempt to establish that the mother was infected in the distant past
and prior to gestation (30, 31).
Mothers who have been confirmed of having acquired the infection during pregnancy or
shortly before gestation (e.g., within 3 months of conception) are at risk for CT. This risk can
be reduced if treatment with spiramycin is initiated. In the United States, spiramycin is
available at no cost only by pursuing an investigational new drug (IND) application through
the Food and Drug Administration (FDA). In regions where screening programs have been
implemented, the diagnosis of maternal infection acquired during gestation is ascertained by
seroconversion. In regions without these programs, maternal serum is usually not available or
is only available late in gestation or at birth when clinical signs suggestive of congenital
infection have been revealed in the fetus, newborn, or infant. With these late serum samples,
only testing at reference laboratories, such as PAMF-TSL, has the potential to determine
whether mothers were likely to have been infected in the distant past and prior to gestation or
during pregnancy. The aim of serological testing in newborns born to these mothers is to
confirm, establish, or exclude the diagnosis of CT. In newborns with positive amniotic fluid
PCR test results, serological testing and follow-up are still recommended in order to further
confirm the diagnosis of CT and to have additional data in cases where the possibility of a
false-positive PCR test result is raised. In newborns with negative amniotic fluid PCR test
results, or those in whom amniocentesis was not performed, serological testing and follow-up
is paramount as a potential diagnostic tool. A newborn serological panel comprised of
Toxoplasma IgG, IgM ISAGA, and IgA should be performed regardless of whether the
amniotic fluid PCR test was performed and its results. The initial serum should be obtained
after 10 days of life in order to avoid misleading results due to potential contamination with
maternal blood. Follow-up serum samples should be tested in parallel with the previous
sample at 1 month, 2 months, and then every 2 months (Fig. 1). Each newborn born to a
mother who has been confirmed of or is suspected to have been infected during gestation or
shortly before conception must be followed up serologically until 12 months of age. The
Toxoplasma IgG will decrease by half every month until its disappearance around month 6 or
7 in uninfected infants but will not disappear by 12 months of age in infected infants. In some
congenitally infected infants, treatment with a pyrimethamine-sulfonamide combination can
lead to negativization of the Toxoplasma IgG during follow-up, creating the false sense that
the infant is not infected. However, in infected infants, discontinuation of the treatment is
followed by a rebound in the Toxoplasma IgG. If IgG remains negative, assuming the infant
is capable of producing IgG, the diagnosis of CT is excluded.
FUTURE DIRECTIONS
The laboratory diagnosis of congenital toxoplasmosis has benefit from various principles and
methods (Table 1). Future research should address the cost and feasibility of detection of
antibodies, DNA, and live parasite in different platforms and body compartments. For
instance, simultaneous detection of multiple analytes in the same assay offers an attractive
option for multiplex detection of Toxoplasma IgG, IgM, and IgA and of antibodies against
other pathogens with the capacity to cause congenital infection (32, 33). The use of platforms
with multiplex capacities can address cost, with the additional benefit that they may be
extended to other infections. In addition, the feasibility of testing for antibodies in body
compartments beyond serum, such as whole blood and saliva, can address cost and patient
convenience (28). Lastly, public health authorities and national policies should address the
need to fund and protect reference centers of excellence for the diagnosis and management of
congenital infections since these infections may not be seen commonly in individual practices
or medical centers but are a source of major morbidity and mortality to the fetus and to
newborns.
Laboratory Diagnosis of Toxoplasma gondii

Infection and Toxoplasmosis
Jose G. Montoya
J Infect Dis (2002) 185 (Supplement_1): S73-S82.
DOI:
https://doi.org/10.1086/338827
Published:
15 February 2002
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Abstract
For the past 40 years, the Toxoplasma Serology Laboratory at the Palo Alto Medical
Foundation Research Institute (TSL-PAMFRI) has been dedicated to the laboratory diagnosis
of Toxoplasma gondii infection and toxoplasmosis. TSL-PAMFRI is the brain child of Jack
S. Remington. Jack's ceaseless devotion to objectivity and uncompromising excellence has
made TSL-PAMFRI the Toxoplasma reference laboratory for the Centers for Disease Control
and Prevention, the US Food and Drug Administration, and health care providers and clinical
laboratories in the United States and other countries. Jack's leadership and vision created,
defined, and significantly contributed to the development of laboratory methods for the
diagnosis of the infection and diseases caused by T. gondii. A summary of the laboratory tests
currently available at TSL-PAMFRI for the diagnosis of infection and disease caused by the
parasite is presented here.
Topic:
child
laboratory
parasites
serologic tests
toxoplasma
toxoplasmosis
infection
brain
diagnosis
laboratory diagnosis
Issue Section:
Articles
General Considerations
The term toxoplasmosis is reserved to describe the clinical or pathological disease caused by
Toxoplasma gondii and T. gondii infection for an asymptomatic primary infection or
persistence of the parasite in tissues (chronic or latent infection) [1].
When considering toxoplasmosis in the differential diagnosis of a patient's illness, it is

important to keep in mind that emphasis should not be placed on whether the patient has or
has not been exposed to cats. Transmission of parasites essentially occurs without knowledge
of the patient and may be unrelated to direct exposure to a cat (e.g., by ingestion of
vegetables or water contaminated with oocysts or ingestion of undercooked meat
contaminated with cysts). On the other hand, patients with an indoor cat that is fed only
cooked food is not at risk of acquiring the infection from that cat. Serologic investigation of a
cat to establish whether it is a potential source of the infection should be discouraged; the
prevalence of T. gondii antibodies among cats in a given locale is usually similar to their
prevalence in humans. Seropositivity in the cat does not predict shedding of oocysts.
For clinical purposes, toxoplasmosis can be divided for convenience into five infection
categories, including those (1) acquired by immunocompetent patients, (2) acquired during
pregnancy, (3) acquired congenitally; and (4) acquired by or reactivated in immunodeficient
patients, and including (5) ocular infections. In any category, clinical presentations are not
specific for toxoplasmosis, and a wide differential diagnosis must be considered.
Furthermore, methods of diagnosis and their interpretations may differ for each clinical
category.
Diagnostic Methods
The diagnosis of T. gondii infection or toxoplasmosis may be established by serologic tests,
amplification of specific nucleic acid sequences (i.e., polymerase chain reaction [PCR]),
histologic demonstration of the parasite and/or its antigens (i.e., immunoperoxidase stain), or
by isolation of the organism [1]. Other rarely used methods include demonstration of
antigenemia and antigen in serum and body fluids, a toxoplasmin skin test, and antigen-
specific lymphocyte transformation [1].
Serologic Tests
The use of serologic tests for demonstration of specific antibody to T. gondii is the initial and
primary method of diagnosis. Different serologic tests often measure different antibodies that
possess unique patterns of rise and fall with time after infection [2]. A combination of
serologic tests is usually required to establish whether an individual has been most likely
infected in the distant past or has been recently infected. The clinician and clinical
laboratories must be familiar with these problems and consult reference laboratories if the
need arises.
A panel of tests (the Toxoplasma Serological Profile [TSP]) consisting of the Sabin-Feldman
dye test (DT) [3], double sandwich IgM ELISA [4], IgA ELISA [5], IgE ELISA [6, 7], and
AC/HS test [8] has been used successfully by our group to determine if serologic test results
are more likely consistent with infection acquired in the recent or more distant past [2, 9, 10].
The AC/HS test is interpreted as previously described [8] by comparing IgG titers obtained
with formalin-fixed tachyzoites (HS antigen) with those obtained with acetone-fixed
tachyzoites (AC antigen).
The TSP has been successfully used in the setting of toxoplasmic lymphadenitis [2],
myocarditis [11], polymyositis [11], and chorioretinitis [10] and during pregnancy [9]. For
sera with positive results in IgG and IgM tests, the discriminatory power of the TSP to
differentiate between recently acquired infection and chronic infection is probably superior to
any other single serologic test.
Current interpretation of results in the TSP at the Toxoplasma Serology Laboratory at the
Palo Alto Medical Foundation Research Institute (TSL-PAMFRI) is as follows: Sera that are
positive in the DT, negative in the IgM, IgA, and IgE ELISAs, and reveal a chronic pattern in
the AC/HS test are typically found in patients infected in the most distant past. The
combination of high titers in the DT, positive IgM, IgA, and IgE ELISAs, and an acute
pattern in the AC/HS test is highly suggestive of a recently acquired infection. In contrast, the
presence of positive DT and IgM ELISA results but a negative, low-positive, or equivocal
result in the IgA and IgE ELISAs and an equivocal pattern in the AC/HS test is more difficult
to interpret. In the latter setting, a follow-up sample is usually obtained, the 2 samples are run
in parallel, and the serologic test titer results are compared. If the titers obtained in the 2
samples do not change significantly, the infection is most likely to have been acquired in the
distant past. In contrast, significant changes (rise or decline) detected in the titers of the 2
samples are considered to be suggestive of a recently acquired infection.
IgG antibodies. The most commonly used tests for the measurement of IgG antibody are the
DT, the ELISA, the IFA, and the modified direct agglutination test [1, 12]. In these tests, IgG
antibodies usually appear within 12 weeks of acquisition of the infection, peak within 12
months, decline at various rates, and usually persist for life.
When two different compounds (i.e., acetone and formalin) are used to fix parasites for use in
the agglutination test, a differential agglutination test (also known as the AC/HS test)
results due to the fact that the different antigenic preparations vary in their ability to
recognize sera obtained during the acute and chronic stages of the infection. This test has
proved useful in helping to differentiate acute from chronic infections [8] but is best used in
combination with a panel of other tests (e.g., the TSP).
Recently, a number of tests for avidity of Toxoplasma IgG antibodies have been introduced to
help discriminate between recently acquired and distant infection [1315]. It has been
observed that the functional affinity of specific IgG antibodies is initially low after primary
antigenic challenge and that it increases during subsequent weeks and months by antigen-
driven B cell selection. Protein-denaturing reagents including urea are used to dissociate the
antibody-antigen complex. The avidity result is determined using the ratios of antibody
titration curves of urea-treated and untreated samples.
IgM antibodies. IgM antibodies may appear earlier and decline more rapidly than IgG
antibodies. The most commonly used tests for the measurement of IgM antibody are double-
sandwich or capture IgM-ELISA kits [4], the IFA test, and the immunosorbent agglutination
assay (IgM-ISAGA; available from bioMrieux) [1]. False-positive results due to rheumatoid
factor and antinuclear antibodies in some IgM-IFA tests are not detected by the most
commonly used commercial double-sandwich or capture IgM-ELISAs [4]. Despite the wide
distribution of commercial test kits to measure IgM antibodies, these tests often have low
specificity, and the reported results are frequently misinterpreted [16, 17].
An IgM test is still used by most laboratories to determine if a patient has been infected
recently or in the distant past, and because of the hurdles posed in interpreting a positive IgM
test result, confirmatory testing should always be performed.
In patients with recently acquired primary infection, T. gondii specific IgM antibodies are
detected initially, and in most cases, these titers become negative within a few months.
However, in some patients, positive T. gondiispecific IgM titers can still be observed
during the chronic phase of infection [16]. Some investigators have reported that IgM
antibodies can be detected as long as 12 years after the acute infection [18]. The persistence
of these IgM antibodies does not appear to have any clinical relevance, and these patients
should be considered chronically infected. Further complicating the interpretation of a
positive IgM test result is the fact that several methods for its detection still may result in a
relatively high frequency of false-positive results [16, 17]. Thus, a positive IgM test result in
a single serum sample can be interpreted as a true-positive result in the setting of a recently
acquired infection, a true-positive result in the setting of an infection acquired in the distant
past, or a false-positive result.
IgA antibodies. IgA antibodies may be detected in sera of acutely infected adults and
congenitally infected infants by use of ELISA or ISAGA [5]. As is true for IgM antibodies to
the parasite, IgA antibodies may persist for many months or more than a year. For this
reason, they are of little additional assistance for diagnosis of acute infection in the adult. In
contrast, the increased sensitivity of IgA assays over IgM assays for diagnosis of congenital
toxoplasmosis represents an advance in diagnosis of the infection in the fetus and newborn.
In a number of newborns with congenital toxoplasmosis and negative IgM antibodies, the
serologic diagnosis has been established by the presence of IgA and IgG antibodies [5].
IgE antibodies. IgE antibodies are detectable by ELISA in sera of acutely infected adults,
congenitally infected infants, and children with congenital toxoplasmic chorioretinitis [6, 7].
Their demonstration does not appear to be particularly useful for diagnosis of T. gondii
infection in the fetus or newborn when compared with IgA tests. The duration of IgE
seropositivity is briefer than that with IgM or IgA antibodies and hence appears useful for
identifying recently acquired infections [2, 7].
PCR
PCR amplification for detection of T. gondii DNA in body fluids and tissues has successfully
been used to diagnose congenital [19], ocular [20, 21], and cerebral and disseminated [22, 23]
toxoplasmosis. PCR has revolutionized the diagnosis of intrauterine T. gondii infection by
enabling an early diagnosis to be made, thereby avoiding the use of more invasive procedures
on the fetus. PCR has enabled detection of T. gondii DNA in brain tissue [24], cerebrospinal
fluid (CSF) [25], vitreous and aqueous fluids [20], bronchoalveolar lavage (BAL) fluid [26],
and blood [23] in patients with AIDS.
Histologic Diagnosis
Demonstration of tachyzoites in tissue sections or smears of body fluid (e.g., CSF or amniotic
or BAL fluids) establishes the diagnosis of the acute infection [1]. It is often difficult to
demonstrate tachyzoites in conventionally stained tissue sections. The immunoperoxidase
technique, which uses antisera to T. gondii, has proven both sensitive and specific: It has been
used successfully to demonstrate the presence of the parasite in the central nervous system
(CNS) of AIDS patients [27]. The immunoperoxidase method is applicable to unfixed or
formalinfixed paraffin-embedded tissue sections [27]. A rapid, technically simple, and under-
used method is the detection of T. gondii in air-dried, Wright-Giemsastained slides of
centrifuged (e.g., cytocentrifuge) sediment of CSF or of brain aspirate or in impression
smears of biopsy tissue. Multiple tissue cysts near an inflammatory necrotic lesion probably
establish the diagnosis of acute infection or reactivation of latent infection.
Isolation of T. gondii
Isolation of T. gondii from blood or body fluids establishes that the infection is acute.
Attempts at isolation of the parasite can be performed by mouse inoculation or inoculation in
tissue cell cultures of virtually any human tissue or body fluid.
Diagnosis of Specific Clinical Entities

The first step in pursuing the diagnosis of T. gondii infection or toxoplasmosis is to determine
whether the individual has been exposed to the parasite. In essentially all cases, any of the
tests for the detection of IgG antibodies reliably establish the presence or absence of the
infection. In a small number of patients, IgG antibodies might not be detected within 23
weeks after the initial exposure to the parasite; however, this is rare. In addition, rare cases of
toxoplasmic chorioretinitis and toxoplasmic encephalitis in immunocompromised patients
have been documented in patients with negative T. gondiispecific IgG antibodies.
The second step consists of establishing whether the patient has a recently acquired infection
or an infection acquired in the more distant past. In general, a true-negative IgM test
essentially rules out that the infection has been acquired in recent months. A positive IgM test
is more difficult to correctly interpret. One must not assume that a positive IgM test result is
diagnostic of recently acquired infection (see above under IgM antibodies in the Serologic
Tests section). Confirmatory testing should be done for all cases for whom IgM test results
are positive [9, 17, 28]. Serologic tests should not be considered useful for measuring
response to therapy.
The third step is to establish whether the patient's condition or illness is due to toxoplasmosis
(recently acquired infection or recrudescence of latent infection) or is unrelated to the
infection.
Toxoplasmosis in the Immunocompetent Patient

The vast majority of cases of T. gondii infection in adults and children are asymptomatic
[29]. Lymphadenopathy is the most common manifestation in the 10%20% percent of
otherwise immunocompetent individuals whose primary T. gondii infection is symptomatic.
Less common presentations in these patients include, but are not limited to, chorioretinitis,
myocarditis, and/or polymyositis [30].
Tests for IgG and IgM antibodies should be used for initial evaluation of these patients.
Testing of serial specimens obtained 34 weeks apart (in parallel) provides the best
discriminatory power if the results in the initial specimen are equivocal. Negative results in
both tests virtually rule out the diagnosis of toxoplasmosis. In rare instances early in
infection, IgG antibodies may not be detectable, whereas IgM antibodies are present (hence
the need for both tests to be performed). Acute infection is supported by documented
seroconversion of IgG and IgM antibodies or a greater than four-fold rise in IgG antibody
titer in sera run in parallel. A single high titer of any immunoglobulin is insufficient to make
the diagnosis since IgG antibodies may persist at high titers for many years [1] and IgM
antibodies may be detectable for >12 months. The TSP, performed on a single serum sample,
is useful in determining the likelihood that the infection is acute.
Characteristic histologic criteria and a TSP consistent with recently acquired infection
establish the diagnosis of toxoplasmic lymphadenitis in older children and adults [2, 31].
Endomyocardial biopsy and biopsy of skeletal muscle has been successfully used to establish
T. gondii as the etiologic agent of myocarditis and polymyositis in immunocompetent
patients [11]. Isolation studies and PCR have rarely proven useful for diagnosis in
immunocompetent patients.
Ocular Toxoplasmosis
Toxoplasmic chorioretinitis may result from congenital or postnatally acquired infection. In
both of these situations, lesions may occur during the acute or latent (chronic) stage of the
infection [10, 32, 33].
Low titers of IgG antibody are usual in patients with active chorioretinitis due to reactivation
of congenital T. gondii infection; IgM antibodies usually are not detected. When sera from
such patients are examined by use of the DT, titers should be first determined with undiluted
serum since in some cases, the conventional initial dilution of 1:16 may be negative.
In most cases, toxoplasmic chorioretinitis is diagnosed by ophthalmologic examination, and

empiric therapy directed against the organism is often instituted on the basis of clinical
findings and serologic test results. In a number of patients, the morphology of the retinal
lesion(s) may be non-diagnostic and/or the response to treatment is suboptimal. In such cases
(unclear clinical diagnosis and/or inadequate clinical response), detection of a local and
increased T. gondii antibody response in ocular fluids (immune load), demonstration of the
parasite by isolation or histopathology, or amplification of T. gondii DNA (in both aqueous
and vitreous fluids) have been used successfully to establish the diagnosis [21, 34, 35].
Toxoplasmosis in the Immunodeficient Patient

In contrast to the relatively favorable course of toxoplasmosis in almost all
immunocompetent individuals, immunologically impaired patients usually develop a dreadful
and often life-threatening disease [36]. Immunocompromised patients at higher risk for
toxoplasmosis include those with hematologic malignancies (particularly patients with
lymphoma), bone marrow transplant, solid organ transplant (including heart, lung, liver, or
kidney), or AIDS.
Toxoplasmic encephalitis is the most common presentation of toxoplasmosis in

immunocompromised patients [36] and is the most frequent cause of focal CNS lesions in
AIDS patients [37]. It is unclear whether T. gondii penetrates the brain more easily than other
organs or whether it is more difficult for the brain, as an immunologically privileged site, to
eradicate the organism during the initial acute infection and once residual infection has been
established [38]. A wide range of clinical findings, including altered mental state, seizures,
weakness, cranial nerve disturbances, sensory abnormalities, cerebellar signs, meningismus,
movement disorders, and neuropsychiatric manifestations are observed in patients with
toxoplasmic encephalitis [39]. Other organs commonly involved in immunocompromised
patients with toxoplasmosis are the lungs, eyes, and heart.
In the vast majority of immunocompromised patients, toxoplasmosis results from reactivation

of a latent infection. In contrast, in heart transplant patients and in a small number of other
immunocompromised patients, the highest risk of developing disease is in the setting of
primary infection (i.e., a seronegative recipient who acquires the parasite from a seropositive
donor via a graft) [40, 41].
Because reactivation of chronic infection is the most common cause of toxoplasmosis in

patients with malignancies or AIDS or in recipients of organ transplants (other than heart
transplants), initial assessment of these patients should routinely include an assay for T.
gondii IgG antibodies. Those with a positive result are at risk of reactivation of the infection;
those with a negative result should be instructed on how they can prevent becoming infected.
When toxoplasmosis is suspected in immunocompromised patients chronically infected with

the parasite (those with documented positive T. gondiispecific IgG antibody prior to the
onset of immunosuppression) additional serologic testing adds very little (or may be
misleading) to the diagnostic evaluation [41, 42]. In these patients, results indicating apparent
reactivation (rising IgG and IgM titers) may be present in the absence of clinically apparent
infection. In addition, serologic test results consistent with chronic infection may be seen in
the presence of toxoplasmosis [36, 42]. Thus, for immunocompromised patients in whom
toxoplasmosis is suspected, additional diagnostic methods to attempt to establish the
diagnosis are strongly recommended. These methods include PCR amplification for detection
of T. gondii DNA in blood or body fluids suspected of being infected, isolation of the parasite
from blood or body fluids that may contain the parasite, and histologic examination of
available tissues with T. gondiispecific stains, such as immunoperoxidase.
When clinical signs suggest involvement of the CNS and/or spinal cord, tests should include
computed tomography or magnetic resonance imaging (MRI) of the brain and/or spinal cord.
Neuroimaging studies of the brain should be considered even if the neurologic examination
does not reveal focal deficits. Empiric antiT. gondii therapy for patients with multiple ring
enhancing brain lesions (usually established by MRI), positive IgG antibody titers against T.
gondii, and advanced immunodeficiency (i.e., CD4 cell count of <200 cells/mm3) is accepted
clinical practice; a clinical and radiologic response to specific antiT. gondii therapy is
considered as supportive of the diagnosis of CNS toxoplasmosis. Brain biopsy should be
considered in immunocompromised patients with presumed CNS toxoplasmosis if there is a
single lesion on MRI, a negative IgG antibody test result, or inadequate clinical response to
an optimal treatment regimen or to what the physician considers to be an effective
prophylactic regimen against T. gondii (e.g., trimethoprimsulfamethoxazole) [30]. If T. gondii
serologic and radiologic studies do not support a recommendation for empiric treatment or
are inconclusive and if brain biopsy is not feasible, a lumbar puncture should be considered if
it is safe to perform; PCR can then be performed on the CSF specimen. CSF can also be used
for isolation studies, although it is uncommon for T. gondii to be isolated from CSF from
immunocompromised patients. Of note, PCR examination of CSF can also be used for
detection of Epstein-Barr virus, JC virus, or cytomegalovirus DNA in patients in whom
primary CNS lymphoma, progressive multifocal leukoencephalopathy, or cytomegalovirus
ventriculitis, respectively, have been considered in the differential diagnosis.
T. gondii Infection in Pregnancy

T. gondii infection acquired during pregnancy may result in severe damage or death of the
fetus and long-term sequelae in offspring. Because congenital toxoplasmosis results almost
solely in women who acquire the infection during gestation, it is critical to determine whether
infection during pregnancy has occurred. The incidence of congenital toxoplasmosis in the
offspring of women infected prior to gestation has been shown to be extremely rare unless a
woman is immunocompromised (e.g., receiving corticosteroids or immunosuppressive drugs
or positive for human immunodeficiency virus [HIV]).
At present in the United States, definitive diagnosis of the acute infection and the time of its
occurrence have been compromised by the lack of systematic screening and the fact that only
a single serum sample is submitted for testing. When only 1 serum sample is available, tests
to detect the presence of IgG and IgM antibodies are most commonly used to determine if a
pregnant woman acquired acute infection during gestation.
A negative IgM test result for a pregnant woman in the first 24 weeks of gestation with a low
IgG test titer (i.e., DT < 1024) essentially places the acquisition of the infection prior to
gestation. In the third trimester, a negative IgM test titer is most likely consistent with a
chronic maternal infection but does not exclude the possibility of an acute infection acquired
early in pregnancy; this is especially true in those patients who exhibit a rapid decline in their
IgM titers during the acute infection. In such cases, the use of other serologic tests (e.g., IgA,
IgE, AC/HS, avidity) may be of particular help.
In contrast, a positive IgM test result requires further assessment with confirmatory serologic
testing. A false positive IgM test result or its erroneous interpretation canbe misleading and
result in unnecessary abortions [9]. Sixty percent of pregnant women with IgM results
determined to be positive by nonreference laboratories were found to be chronically infected
whentested atTSL-PAMFRI[9]. The potential pitfalls of relying solely on an IgM test as a
discriminatory method to allow such distinction and the low reliability of commercial T.
gondiispecific IgM kits when positive results are obtained have been reported by our group
and others [16, 17].
Thus, it is recommended that a positive IgM test result should always undergo confirmatory
testing at a reference laboratory [16, 17]. In sera with a positive IgM test result, the TSP has
been used to help discriminate between recently acquired and distant infection [2, 9].
A number of tests for avidity of Toxoplasma IgG antibodies have been introduced recently to
help discriminate between recently acquired and distant infection [1315]. More recently, we
reported the usefulness of testing for avidity of IgG in the setting of pregnant women in their
first 12 weeks of gestation at TSL-PAMFRI [15]. Measurement of IgG avidity was performed
with a T. gondii IgG avidity EIA (Labsystems) method. With this method, a high avidity has
been stated to exclude that the infection occurred in the previous 12 weeks. Thus, its greatest
value is in sera obtained from pregnant women in their first trimester of gestation.
Whether the avidity test can replace any of the present tests in the TSP or simply be added to
that panel requires further evaluation of the avidity tests being marketed. No avidity test has
been released by the US Food and Drug Administration for marketing in the United States.
We now routinely employ the avidity test as an additional confirmatory diagnostic tool in the
TSP for those patients with a positive and/or equivocal IgM test result or acute and/or
equivocal pattern in the AC/HS test. Health care providers and clinical laboratories involved
in the care of pregnant women should be aware that avidity testing is only a confirmatory test
and not the ultimate test for decision making. Its highest value is observed when high IgG
avidity antibodies are detected and the serum is obtained during the time window of
exclusion of acute infection for a particular method (i.e., 12 weeks for the Labsystems
method and 16 weeks for the Vidas immunoassay [bioMrieux]).
Once the diagnosis of acute acquired infection during pregnancy has been presumptively
established, diagnostic efforts should then focus on determining whether the fetus has been
infected.
Congenital Infection in the Fetus and Newborn

Prenatal diagnosis. Prenatal diagnosis of fetal infection is advised when a diagnosis of acute
infection is established or highly suspected in a pregnant woman or an abnormality in the
fetus suggests congenital toxoplasmosis. Methods to obtain fetal blood, such as periumbilical
fetal blood sampling, have been largely abandoned because of the risk involved for the fetus
and the delay in obtaining definitive results with conventional parasitologic tests [43].
Prenatal diagnosis of congenital toxoplasmosis is currently based on ultrasonography and

amniocentesis. PCR on amniotic fluid for detection of T. gondiispecific DNA performed
from 18 weeks onwards of gestation should be used in all cases of established acute maternal
infection or cases with serologic test results highly suggestive of acute acquired infection
during pregnancy [43]. In a recent report, the overall sensitivity of PCR on amniotic fluid was
estimated to be 64%, the negative predictive value was estimated to be 87.8%, and specificity
and positive predictive value were estimated to be 100% [44]; in this study, marked
differences in sensitivity were observed depending on the gestational age at the time of the
amniocentesis [44]. The reliability of the PCR test before 18 weeks of gestational age is
unknown [43, 44]. PCR on amniotic fluid is not recommended for HIV-infected women
because of the risk of transmitting the HIV virus to the fetus during the amniocentesis
procedure.
Diagnosis in the newborn. Maternal IgG antibodies present in the newborn may reflect either
past or recent infection in the mother. For this reason, tests for detection of IgA and IgM
antibodies are commonly employed for diagnosis of infection in the newborn. Serum samples
obtained from peripheral blood are preferred. Samples from umbilical cord should not be
used as they may be contaminated with maternal blood. Demonstration of IgA antibodies
appears to be more sensitive than detection of IgM antibodies for establishing infection in the
newborn [5]. T. gondiispecific IgA may be present when there is no T. gondiispecific
IgM, and the converse may also occur. If IgA antibodies are detected in the newborn, the test
should be repeated at 10 days after birth to make certain that what is being measured is not
contaminating maternal IgA antibodies. In addition, if the newborn has received a blood
transfusion, serologic tests may measure exogenously administered rather than endogenous
antibody.
Infants born to mothers chronically infected with T. gondii will have maternal Toxoplasma-
specific IgG antibodies detected in their peripheral blood. In these infants, Toxoplasma
serologic tests for IgM and IgA antibodies are usually negative, and efforts to detect T. gondii
in body fluids or tissues (by isolation or PCR) should yield negative results. Follow-up
serologic testing should be done on these patients until the IgG antibodies become
undetectable. Maternally transferred IgG antibodies should disappear within the first 612
months of life. A negative T. gondiispecific IgG test result at 1 year of age essentially rules
out congenital toxoplasmosis.
Additional diagnostic methods that have been used successfully to diagnose the infection in
infants include direct demonstration of the organism by isolation of the parasite (e.g., mouse
inoculation or inoculation in tissue cultures of CSF, urine, placental tissue, or peripheral
blood) and amplification of T. gondiispecific DNA (e.g., PCR in CSF, peripheral blood, or
urine) [1]. Evaluation of infants with suspected congenital toxoplasmosis should always
include ophthalmologic examination, non-contrast computed tomography or ultrasound of the
brain (to determine whether hydrocephalus or calcifications are present), and examination of
CSF [1]. Detection of calcifications in the brain of a newborn by x-ray, ultrasound, or
computed tomography should heighten the suspicion of T. gondii as the cause of the disease.
In severely affected infants with congenital toxoplasmosis, unilateral or, more often, bilateral
and symmetric dilatation of the ventricles is not an uncommon finding [1]. Persistent CSF
pleocytosis and elevated protein content should lead the physician to consider a diagnosis of
congenital toxoplasmosis even in subclinical cases [1].
Although not clinically available, antigen-specific lymphocyte transformation and

lymphocyte typing in response to exposure to T. gondii antigens has been used successfully
to diagnose the congenital infection in infants 2 months of age [45, 46]. Specific
lymphocyte anergy to the organism may also occur in congenitally infected infants [47].
Summary
The diagnosis of T. gondii infection or toxoplasmosis can be established by serologic tests,
PCR, histologic examination, or isolation of the parasite. T. gondii infection can be
asymptomatic, and the clinical manifestations of patients with symptomatic toxoplasmosis
are protean and nonspecific. The choice of the appropriate diagnostic method(s) and its (their)
interpretation may differ for each clinical category (i.e., immunocompetent vs.
immunodeficient patient). Reference laboratories should be contacted prior to diagnostic
procedures to optimize the choice and handling of the specimens and their yield.
At the dawn of the twenty-first century, TSL-PAMFRI offers state-of-the-art diagnostic

methods and consultation for clinicians who encounter patients with diagnosed or suspected
T. gondii infection or toxoplasmosis. Today, this is only possible thanks to Jack S.
Remington's uninterrupted efforts and leadership during the last 4 decades in advancing the
understanding, diagnosis, and treatment of the infection and diseases caused by T. gondii.
Acknowledgments
Jack's well-known reputation for attention to detail and objectivity is portrayed in figure 1.
The examples of the manuscripts and chapter shown here could easily be on its fourth or fifth
draft. For his more than 700 publications, Jack's vision and endless pursuit of perfection
made it possible that such a draft could end up as a full publication in a journal or book. He
has the legendary capacity to transform what appears chaotic, unrelated, and fragmented into
what is logical, complete, and relevant. We, his fellows, owe him an immense debt of
gratitude and respect and want to thank him for all the help and guidance he has provided us.

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Transaxial contrast-enhanced computed tomography scan in a 24-year-old man with human

Congenital toxoplasmosis may be associated with anomalies such as microcephaly,

Magnetic resonance imaging (MRI) is considered superior to computed tomography (CT)

Congenital toxoplasmosis as well as congenital cerebral toxoplasmosis are discussed

In immunocompetent patients, acute encephalitis is extremely rare. Even in the

Pathologically, parenchymal toxoplasma lesions have three distinct zones:

a central avascular zone of coagulative necrosis

Typically, cerebral toxoplasmosis appears as multiple hypodense regions predominantly in

enhancement: following administration of contrast there is nodular or ring enhancement

T1: may be difficult to identify, but are typically isointense or hypointense 5

PET/CT scan and thallium SPECT

Minimal or no uptake (cold lesion) as opposed to primary CNS lymphoma 7.

Treatment and prognosis

Treatment consists of sulfadiazine with pyrimethamine 6.

General imaging differential considerations include:

primary CNS lymphoma: see lymphoma vs toxoplasmosis

Cases and Figures

Figure 1: histology showing tachyzoites and encysted bradyzoites

Case 3: acute necrotizing toxoplasma encephalitis

Imaging Differential Diagnosis

Primary CNS lymphoma

Received: 03 May 012

How to cite this article

Madi D, Achappa B, Rao S, Ramapuram JT, Mahalingam S. Successful Treatment of

How to cite this URL

Madi D, Achappa B, Rao S, Ramapuram JT, Mahalingam S. Successful Treatment of

Toxoplasmosis is caused by infection with the obligate intracellular parasite Toxoplasma

A 30-year-old male known case of retroviral disease presented to Kasturba Medical

Keywords: Cerebral toxoplasmosis; Clindamycin; HIV/AIDS.

A 30-year-old male presented to Kasturba Medical College, India, with complaints of

CT scan typically reveals bilateral, multiple, hypodense ring-enhancing lesions with

Cerebral toxoplasmosis is generally treated empirically in AIDS patients with compatible

Trimethoprim/sulfamethoxazole is an alternative treatment for toxoplasma encephalitis

Cerebral toxoplasmosis can be treated with clindamycin without pyrimethamine in resource

7. Torre D, Speranza F, Martegani R, Zeroli C, Banfi M, Airoldi M. A retrospective study of treatment of

was identified as an agent of infectious disease in 1932 when it was discovered in a

fatal disease in adults due to several cases of toxoplasma encephalitis found in

hematologic cancer patients. [2]

1. Toxoplasmosis is transmitted to humans by way of the tissue form of T. gondii through

Specific Microbial Characteristics:

Specific Tests for Identification:

Serologic testing, which measures immunoglobulin G (IgG), is used to diagnose

Signs and Symptoms:

Prevention and Treatment:

[1] Government Food Safety Information. Toxoplasmosis.

[4] LeLand Stanford Junior University. Parasites and Pestilence. 2007.

[6] Alison Keith. Toxoplasmosis. Last updated March 1, 2010.

[7] Citizendium. Toxoplasma gondii. Last updated October 30, 2013.

[14] Mayo Clinic. Treatment and Drugs. January 24, 2011.

[16] Canada Communicable Disease Report. Outbreak of Toxoplasmosis Associated with

Laboratory Diagnosis of Congenital

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Effective anti-Toxoplasma treatment, when instituted as early as in utero during the

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The diagnosis of CT can be confirmed or excluded more accurately when comprehensive

Ideally, it should be established first whether the mother is immunocompromised or

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