TOXOPLASMOSIS

Definition

 Toxoplasmosis is the disease caused by infection with the obligate

intracellular parasite Toxoplasma gondii.
 Both acute and chronic toxoplasmosis are conditions in which the
parasite is responsible for the development of clinically evident disease,
including lymphadenopathy, encephalitis, myocarditis, and pneumonitis.

Transmission

 Oral Transmission
 Transmission via Blood or Organs
 Transplacental Transmission

Pathology

 Cell death and focal necrosis due to replicating tachyzoites induce an

intense mononuclear inflammatory response in any tissue or cell type
infected.
 Immunofluorescence staining with parasitic antigen-specific antibodies
can reveal either the organism itself or evidence of antigen.
 Once the cysts reach maturity, the inflammatory process can no longer be
detected, and the cysts remain immunologically quiescent within the
brain matrix until they rupture.

Clinical manifestations

 In persons whose immune systems are intact, acute toxoplasmosis is

usually asymptomatic and self-limited.
 This condition can go unrecognized in 80 to 90% of adults and children
with acquired infection.
 In contrast, the wide range of clinical manifestations in congenitally
infected children includes severe neurologic complications such as
hydrocephalus, microcephaly, mental retardation, and chorioretinitis.
 If prenatal infection is severe, multiorgan failure and subsequent
intrauterine fetal death can occur.
 In children and adults, chronic infection can persist throughout life, with
little consequence to the immunocompetent host.

Toxoplasmosis in the Immunocompetent Person

 The most common manifestation of acute toxoplasmosis is cervical

lymphadenopathy.
 The nodes may be single or multiple, are usually nontender, are discrete,
and vary in firmness.
 Lymphadenopathy also may be found in suboccipital, supraclavicular,
inguinal, and mediastinal areas.
 Between 20 and 40% of patients with lymphadenopathy also have
headache, malaise, fatigue, and fever [usually with a temperature of
<40°C (<104°F)].

Infection of the Immunocompromised Person

 Patients with AIDS and those receiving immunosuppressive therapy for

lymphoproliferative disorders are at greatest risk for developing acute
toxoplasmosis.
 In individuals with AIDS, more than 95% of cases of Toxoplasma
encephalitis are believed to be due to recrudescent infection.
 In most of these cases, encephalitis develops when the CD4+ cell count
falls below 100/uL.
 In the immunocompromised individual, the disease may be rapidly fatal
if untreated.
 Toxoplasmosis is a principal opportunistic infection of the CNS in
persons with AIDS.
 Individuals with AIDS who are seropositive for T. gondii are at a very
high risk for developing encephalitis.
 The signs and symptoms of acute toxoplasmosis in the
immunocompromised patient are principally within the CNS.
 More than 50% of patients with clinical manifestations have intracerebral
involvement.
 Clinical findings at the time of presentation range from nonfocal to focal
dysfunction.
 These findings include encephalopathy, meningoencephalitis, and mass
lesions.
 Patients may present with altered mental status (75%), fever (10 to 72%),
seizures (33%), headaches (56%), and focal neurologic findings (60%),
including motor deficits, cranial nerve palsies, movement disorders,
dysmetria, visual-field loss, and aphasia.
 Patients who present with evidence of diffuse cortical dysfunction
develop evidence of focal neurologic disease as the infection progresses.
 This altered condition is due not only to the necrotizing encephalitis
caused by direct invasion of the parasite but also to secondary effects,
including vasculitis, edema, and hemorrhage.
 The onset of infection can range from an insidious process over several
weeks to an acute confusional state with fulminant focal deficits,
including hemiparesis, hemiplegia, visual-field defects, localized
headache, and focal seizures.
 Although lesions can occur anywhere within the CNS, the areas most
involved appear to be the brainstem, basal ganglia, pituitary gland, and
corticomedullary junction.
 Brainstem involvement gives rise to a variety of neurologic dysfunctions,
including cranial nerve palsy, dysmetria, and ataxia.
 With basal ganglionic infection, patients may develop hydrocephalus,
choreiform movements, and choreoathetosis.
 The differential diagnosis includes herpes simplex encephalitis,
cryptococcal meningitis, progressive multifocal leukoencephalopathy,
and primary CNS lymphoma
 More than 97% of patients with AIDS and toxoplasmosis have IgG
antibody to the parasite in their sera.
 Neuroradiologic evaluation should include double-dose contrast
computed tomography (CT) of the head.
 By this test, single and frequently multiple contrast-enhancing lesions
(<2 cm), ring-enhancing lesion, may be identified.
 Magnetic resonance imaging (MRI) usually demonstrates multiple
lesions and provides a more sensitive evaluation of the efficacy of
therapy than does CT.

Diagnosis

Serology:

 Serologic testing has become the routine method of diagnosis.

 Diagnosis of acute infection with T. gondii can be established by
detection of the simultaneous presence of IgG and IgM antibody to
Toxoplasma in serum.
 The presence of circulating IgA favors the diagnosis of an acute
infection.
 The Sabin-Feldman dye test, the indirect fluorescent antibody test, and
the enzyme-linked immunosorbent assay (ELISA) all satisfactorily
measure circulating IgG antibody to Toxoplasma.
 Positive IgG titers (>1:10) can be detected as early as 2 to 3 weeks after
infection.
 The Immunocompromised Host: in patients with AIDS, the presence of
IgG and radiologic findings consistent with toxoplasmosis are grounds
for a presumptive diagnosis.
 Patients with toxoplasmic encephalitis have focal or multifocal
abnormalities demonstrable by CT or MRI.

Treatment

 Current therapeutic protocols are directed at folate metabolism, protein

synthesis, or nucleic acid synthesis of the parasite.
 Pyrimethamine and trimethoprim inhibit the enzyme dihydrofolate
reductase.
 Inhibitors of protein synthesis, including clindamycin, chlortetracycline,
and azithromycin, affect growth of the parasite
 Inhibitors of purine synthesis, such as arprinocid, may prove to be
important.
 Atovaquone, which blocks pyrimidine salvage, has demonstrated activity
against both T. gondii and P. carinii.
 Infection in Immunocompromised Patients: The mainstay of treatment
for Toxoplasma encephalitis in immunocompromised patients is a
combination regimen.
 Administered together for 4 to 6 weeks or until radiologic improvement
is documented pyrimethamine (a 200-mg loading dose followed by 50 to
75 mg/d) and sulfadiazine (4 to 6 g/d in four divided doses) block folic
acid metabolism and reduce the parasite burden.
 Leucovorin (calcium folinate, 10 to 15 mg/d) is given as an adjunct to
prevent the bone marrow toxicity associated with pyrimethamine.
 Both pyrimethamine and sulfadiazine cross the blood-brain barrier.
 Pyrimethamine and sulfadiazine are active only against the tachyzoite
stage of the parasite.
 Alternative Regimens: Dapsone (diaminodiphenyl sulfone), with its
longer serum half-life and decreased toxicity, is an effective alternative
to sulfadiazine.
 Clindamycin is well absorbed from the gastrointestinal tract, and serum
levels peak 1 to 2 h after administration.
 The combination of oral pyrimethamine (25 to 75 mg/d) plus intravenous
clindamycin (1200 to 4800 mg/d) is effective for patients with AIDS
who have Toxoplasma encephalitis.
 Other macrolides that have been evaluated include roxithromycin,
clarithromycin, and azithromycin.
 Evidence suggests that the macrolides are not beneficial by themselves,
but a combination of pyrimethamine and clarithromycin appears to be
effective.
 Atovaquone (750 mg tid or qid) is an optional agent for the treatment of
individuals who are intolerant of other agents.

Ampath protocol

 Start anticonvulsant therapy

 Sulphadiazine 1gm qid (IV or oral) + pyrimethamine 75-100 mg od x 3
days, then reduce to 50-75 mg od + folinic acid
 Alternative treatment
 Fansidar 8,4,4,4
 Dapsone 100mg od
 Clindamycin 600mg (IV or po) qid
 Atovaquone 750mg po qid

Maintenance Therapy

 Necessary to prevent recurrence

 Use Dapsone 100 mg od + pyrimethamine 25-50 mg od + folinic acid 15
mg od
 Monitor blood picture every 3-6 m