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Management of

Toxoplasmosis
dr. Rizky Perdana,SpPD,KPTI,FINASIM

Case

Woman, 25 years old


NO symptoms and signs of infections
Serology test for toxoplasma :

IgM (+) and IgG (+)

Plans to married
????

Case

Man, 30 years old


No Symptoms, only
lymphadenopathy on cervical
Lab test :

PCR TB (-)
Serology test for toxoplasma :
IgM (+) and IgG (+)

??????

Case

Women, 25 years old


First pregnancy
First trimester gestational age
No symptoms and signs
Serology test for toxoplasma :

IgM (+) and IgG (+)

??????

Case

Man, 18 years old


HIV-AIDS (+)
Lymphadenopathy, malaise, loss of
body weight
Serology test for toxoplasma :

IgM (-) and IgG (+)

?????

Toxoplasma: Human
Transmission

Infection in humans typically through ingestion

Raw/undercooked meat
Estimated to occur in of T. gondii infections in U.S.
Parasite isolated from 32% pork chops, 4% lamb
chops (1960s)

Ingestions of oocyst from cat feces or soil


Water or food contaminated with oocysts

Also transplacental transmission

Mother acquires infection during gestation

Toxoplasma Transmission

Toxoplasmosis

Toxoplasmosis: Clinical
Signs

Usually asymptomatic (80-90%)


Flu-like illness
Lymphadenopathy
Self-limiting
Toxoplasmic encephalitis (AIDS)
Congenital toxoplasmosis
Retinochoroiditis

Clinical Signs

Toxoplasmosis encephalitis

Congenital Toxoplasmosis

Ocular Toxoplasmosis
Lymphadenopathy

Differential Diagnosis of
Lymphadenopathy
Toxoplasmosi
s

Inf. Mono

Lymphoma

+++

+++

+++

+++

+++

Atypical Lymphocytes

++++

Anemia

+++

Positive Heterophil

++++

Altered Liver Function

++++

++

Hilar
Lymphadenopathy

+++

Reticulum

Germinal

Bizarre

Lymphadenopathy
Without Other
Symptoms
Pharyngitis
Monocytosis,
Eosinophilia

Lymph Node

Toxoplasma infection

Healthy human usually only mild


symptoms the parasites are killed
by antibody.

Antibody cannot enter brain and eye,


nervous cell cannot regenerate
Central Nervous System are common
target destruction.

Ring-enhancing lesion

Toxoplasmosis ocular
lesions

Toxoplasma: At Risk for


Severe Disease

Congenitally infected fetuses and newborns

Estimated 400-4000 cases each year in the U.S.

Immunologically impaired individuals, most


commonly with defects in T-cell-mediated
immunity

Hematologic malignancies
Bone marrow and solid organ transplants
AIDS, e.g. leading to toxoplasmic encephalitis

Toxoplasmosis in
Pregnancy
Primary infection in
first semester
pregnant women
abortus, still birth, or
congenital
toxoplasmosis

Congenital
Toxoplasmosis

Congenital
Toxoplasmosis

H I V
Immunity

CD4 < 200


Opportunistic infections
RSCM*
Candidosis oro-pharyngeal
Tuberculosis
Cytomegalovirus
Enchepalitis Toxoplasma+
Pneumonia P.carinii (PCP)

80.8%
40.1%
28.8%
17.3%
13.4%

* Djauzi S, Djoerban Z (Ed). Penatalaksanaan infeksi HIV di pelayanan kesehatan dasar. Edisi
kedua.
Jakarta: Balai Penerbit FKUI; 2003
+
Tanpa konfirmasi laboratorium

Toxoplasma: Diagnosis

Serologic testing.
Observation of parasites in patient
specimens.
Isolation of parasites from blood or
other body fluids, by intraperitoneal
inoculation into mice or tissue culture.
PCR (for congenital infections in
utero).

Blood Test Procedure in


Pregnancy

Test 1
(before 2
months of
pregnancy)
IgG +ve (any
titer);
IgM -ve

Serologic Detection of
Toxoplasma During
Pregnancy
Test 2
(in second trimester)

Test 3
(in third
trimester)

No test;

No test;

No treatment

No treatment

Group
I infection before
pregnancy;
No risk (Note 1)

IgG +ve

Repeat IgG after 3


weeks;

II Possible infection soon


after conception;

IgM +ve

Treat if high or rising


titer

Slight risk (Note 2)

IgG -ve

Treat if IgG +ve;

Treat if IgG +ve;

III No previous infection;

IgM -ve

Dont treat if IgG -ve

Dont treat if IgG


-ve

If seroconversion, high risk


(Note 3)

Test serum for presence of Toxoplasma-specific IgG


antibodies
IgG Negative :

IgG Positive :

Not infected

Infected

Retest in 3 weeks if acute infection


suspected

To determine approximate time of infection, test serum for presence of


Toxoplasma-specific IgM antibodies

IgG Positive, IgM Negative:

IgG Negative, IgM Positive:

Infected for more than 6


month

Infected within last 2 years or


false-positive IgM result

Test serum for IgG avidity status

IgG avidity high:

IgG avidity low:

Infected at least 12 weeks


previously

Recent Infection possible

Obtain 2nd sample 3 weeks after 1st sent both


samples to a Toxoplasma Reference Laboratory
for confirmation before any intervention

Latent Toxoplasmosis and Active


Infection in HIV-positive Patients
Cohort 715 HIV (+)
IgG Anti-T.gondii
360 (+)
47 43 cerebral
3 ocular
1 B.M.

355 (-)

After
Four Years
Acute Toxoplasmosis

Yes 13 %*
30 % IgG rise
3 6 % IgM
18 % IgA

No 3 %

Yes 0.3 %*

No

NPV = 99.7 %
Zufferrey J, et al. Eur J Clin Microb Infect Dis 1993 ;12:590-5

Toxoplasmosis: Treatment

Consideration should NOT depend on


cat exposure.
Treatment may or may not be
indicated based on presence of active
disease, immune status, site of
infection.
Prevention most important in
seronegative pregnant women and
immunodeficient patients.

Drugs Of Choice :
and

Pyrimethamin
e

Sulfadoxine

NH2

H3CO
NH2

Cl
N
C2H5

H2N

Mode of action:
1. Pyrimethamine inhibits DNA synthesis by
interfering with folate synthesis.
2. Sulfadoxine prevents PABA synthesis by
inhibiting the enzyme dihydropteroate
synthetase.

OCH3

SO2NH
N

Alternate Drugs :
Spiramycin

and

Mode of action:

1. Spiramycin inhibits RNA synthesis.


2. Sulfadiazine inhibits PABA synthesis
by interfering dihydropteroate synthetase.

Sulfadiazine

Immunologically Normal
Patients
Toxoplasma
infection

Regimen suggested

Acute illness without


lymphadenopathy

No specific tx unless severe/persistent


symptoms or evidence of vital organ
damage

Acquired via
transfusion (lab.
accident)

Treat as for acute chorioretinitis

Active
Chorioretinitis;

[Pyrimetamine 200mg once on 1st day 50-75


mg(q24h)] + [Sulfadiazine 1-1.5 mg po qid] +
[Leucovorine (folinic acid) 5-20 mg 3x/week]
# treat beyond resolution of signs/symptoms; cont

meningitis, lowered
resistance due to
steroids or cytotoxic
drugs

Acute in pregnant
women

Leucovorin 1 week after stopping Pyr.

Spiramycin 827-2335 mg po q8h (w/o food)


until term The
or until
Sanford
fetal
Guideinfection
To Antimicrobial Therapy 2007

Acquired Immunodeficiency Syndrome


(AIDS)
Toxoplasma
Cerebral
Toxoplasmosi
s

Primary
prophylaxis
AIDS pts-IgG toxo
antibody + CD4
count < 100/mcl

Suppresive
treatment

Primary treatment

Alternative treatment

[Pyrimetamine 200mg x 1 po
then 75 mg/day po] +
[Sulfadiazine 1-1.5 mg po
q6h] + [Leucovorine (folinic
acid) 10-20 mg/day po] treat
4-6 week after resolution of
signs/symptoms and then
suppresive tx
OR

Pyrimetamine + folinic
acid (as in primary regimen)
+ 1 of the following =
Clinda 600 mg po/iv q6h
Clarithro 1 gm po bid
Azithro 1.2-1.5 gm po q24h
Atovaquone 750 mg po q6h

TMP-SMX 10-50 mg/kg/day po or


iv divided q12h x 30 days

treat 4-6 week after


resolution of
signs/symptoms and then
suppresive tx

TMP-SMX-DS 1 tab po q24h


OR
TMP-SMX-SS 1 tab po q24h

Dapsone 50 mg po q24h +
Pyrimetamine 50 mg po q
wk
OR

Atovaquone 1500 mg po
q24h
Sulfadiazine 500-1000 mg po 4
x/day + (folinic acid) 10-25 mg

Clinda 300-450 mg q6-8h +


Pyrimetamine 25-50 mg po
q24h
po q24h
The Sanford Guide
ORTo Antimicrobial Therapy 2007
DC if CD4 count > 200 x 3 mo

Prevention and Control

Education

Avoid ingestion of and contact with cysts or


sporulated oocysts
Cook meat to well done with no visible pink in
center
Wash hands thoroughly after handling raw meat
or vegetables
Avoid areas with cat feces
Change litter every day (before sporulation)
Wear disposable gloves when disposing of cat
litter, working in garden, cleaning childs sandbox

Serologic screening for pregnant women