Toxoplasomosis

OUTLINE
Life cycle
Epidemiology
Prevalence
CNS Toxoplasmosis in immune competent
patients
Brief discussion of case report
Diagnosis
Treatment


LIFE CYCLE
Toxoplasma gondii is an intracellular parasite
Felines are only animals in which T gondii can
complete its reproductive cycle
Ingestion>>infects gut epithelium and
reproduces>>oocyst excreted in feces>>ingestion
by non felines>>>organism invade intestinal
epithelium and disseminate throughout
body>>encyst and can lie dormant in any nucleated
cells within tissues for life of host

EPIDEMIOLOGY
Route of transmission
Vertical transmission from infected mother to fetus
Blood transfusion or organ transplant
Ingestion of infectious oocyst from environment,
usually soil contaminated with feline feces
Ingestion of tissue cysts in meat from infected
animal
EPIDEMIOLOGY
Ingestion of undercooked meat is responsible
for majority of toxo cases in some parts of
world, ie France
In most underdeveloped countries more
secondary to environmental exposure
PREVALENCE
Prevalence vary: In US 15.8% age 12-49
seropositive for T. gondii (incidence higher in
nonhispanic blacks compared to nonhispanic
whites and in persons born outside of US)
Some European countries ie France and in some
developing countries prevalence can be as high as
87%


CNS TOXOPLASMOSIS
80-90% of acute T. gondii infections in
immunecompetent hosts are asymptomatic
If there are symptoms, most common are bilateral tender
cervical adenopathy or elsewhere (i.e. intrabdominal and
retroperitoneal)
20-30% will have generalized LAD
Some have mild constitutional symptoms (f/c/sweats)
HAs, myalgias, pharyngitis, diffuse nonpuritic maculopapular
rash, HSM
Benign, self-limited course from weeks to months
CNS TOXOPLASMOSIS
Extremely rare cases of severe disease in
immuncompetent patients have been reported:
pneumonitis, ARDS, myocarditis, pericarditis,
polymyositis, hepatitis or encephalitis
In HIV patients with CD4 <100 who are
seropositive and not receiving effective
prophylaxis has 30% probability of developing
reactivated toxo

CASE REPORT
Kaushik et al in Transactions of Royal Society of
Tropical Medicine and Hygiene (2005) did a case
report of a 28 year old woman who presented
with low grade fever, HA, vomitting x2 months
Initially treated for symptoms and on thyroid
replacement therapy, but then referred to Himalayan
Institute of Medical Sciences in Uttaranchal, India
when symptoms worsened
Vitals: 37.8 120/80
CASE REPORT
Relative lymphopenia 17% (20-40)
ESR elevated 65 (1-25)
Neg VDRL
T4 and T3 lower side of normal; TSH elevated
21 (0.5-4.7)
HIV-1 and HIV-2 negative
CSF: increased opening pressures 240 (50-180);
TNC 495 (45% N, 55% L); prot 210 (15-50);
gluc 24 (40-70 or 60% FG(pts fg 105))
CASE REPORT
CSF neg AFB, crypto and other organisms
CSF culture neg
CXR nl
CT contrast of head-multiple ring enhancing
lesions with moderate hydrocephalus with
meningeal enhancement
Initially treated for tuberculosis
meningoencephalitis and hypothyroidism as TB
is common in Uttaranchal, India
CASE REPORT
Pt without improvement on Rifampin, INH,
Ethambutol , ciprofloxacin and pyrazinamide
and dexamethasone
After 10 days MRI-multiple ring lesions in both
cerebral hemispheres including thalamus and
basal ganglia, pons, middle cerebellar peduncles
assoc with perifocal edema; moderate dilatation
of lateral, 3
rd
and 4
th
ventricles

CASE REPORT
CD4 674
Repeat CSF with improvement in cell count, but
increase in CSF protein
IgG and IgM positive antibodies
Nl serum IgA, IgG, IgM
Pt started on DS bactrim bid x 6wks with
prednisalone 60 qday

CASE REPORT
Pt showed improvement in 3 days
Repeat CSF normal
IgG and IgM toxo antibody titers trended down
Repeat brain MRI in 6 wks showed regression of
lesions
Repeat HIV-1 and HIV-2 in 3 months remained
normal
CNS TOXOPLASMOSIS
In one study by Carme et al 2002, of 16 patients with
severe toxoplasmosis in immunocompetent adults in
French Guiana, 0 had meningeal involvment
Largest series of cases with neurological involvement
in immunecompetent subjects reported by French
reference unit in Paris over a 13 year period (1982-
1995) with 6 reported cases (Couvreur and Thulliez,
1996)

DIAGNOSIS
Lab findings: slight lymphocytosis or atypical lymphocytes; ?
Hepatic transaminase
Pathology
Immunoperoxidase or fluorescent antibody stain
Culture (blood, csf, tissue)
PCR (blood, csf, tissue)
Serologies via ELISA, Sabin-Feldman dye test (gold standard, a
neutrilazation assay in which live organisms lysed in presence of
complement and IgG antibody), Indirect fluorescent antibody
(no live organisms), Immunosorbent agglutination assay
(measures antibody by causing agglutination of acetone or
formalin-preserved whole organism), IgG avidity test (IgG
antibodies made early in infection binds less advidly than
antibodies made later)

DIAGNOSIS
IgG appear within 2 weeks of infection, peak in 6-8
wks, then decline over next 2 years, but detectable
for life
IgM within first week and decline within a few
months, however can persist for years after initial
infection (therefore can not be used to confirm
recent or acute infection)
Acute infection can be confirmed by culture,
documented seroconversion, or 2-fold rise in
antibody level

DIAGNOSIS
MRI more sensitive than CT
SPECT imaging
Brain biopsy-definitive diagnosis; organism
demonstrated on hematoxylin and eosin stains,
some labs use immunoperoxidase staining
MRI WITH RING ENHANCING
LESIONS

THALIUM SPECTROMETRY-
CNS LYPHOMA

BRADYZOITES FROM BRAIN
BIOPSY

BRAIN ABSCESS

TREATMENT
Immunocompetent, nonpregnant patients
generally do not require treatment unless
symptoms severe and prolonged, treatment
usually 2-4 weeks with lower dose
CNS Toxo
Generally responds promptly, lack of clinical or
radiologic improvement within 10-14 days of
emperic therapy for toxo should raise possibility of
alternative diagnosis

TREATMENT
CDC guidelines:
First line: Pyramethamine 200 mg loading dose
followed by 75 mg qday and sulfadiazine 6-8g/day
qid plus folinic acid 10-25 mg qday
For those with allergies to sulfadiazine replace with
clindamycin 600-1200 mg IV or 450 mg PO qid
Alternative therapy:
Pyramethamine and azithromycin 1200-1500 qday
Pyramethamine and atovaquone 750 qid
Sulfadiazine 1500 mg qid and atovaquone 1500 bid
TREATMENT
Duration of therapy is approx 6 weeks
Steroids can be used in addition with patients who
have radiographic evidence of midline shift, elevated
intracranial pressures or clinical deterioration within
first 48 hours
Anticonvulsants if history of seizures
TREATMENT
Response to therapy
Clinical improvement precedes radiographic
improvement
Neuro checks during first 2 weeks more important
Literature response to therapy hampered by
presumptive diagnosis, cross-over treatments and
discontinuation 2/2 toxcity. Comparative trials on
different treatment regimens suggest approx 80%
demonstrate clinical and radiologic responses
REFERENCES
Uptodate
Kaushik, R M; Mahajan, S; Sharma, A; Kaushik
R; Kukreti, R. Toxoplasmic meningoencephalitis
in an immunocompetent host