Toxoplasmosis Clinical Presentation

Only 10-20% of toxoplasmosis cases in adults and children are symptomatic. Toxoplasmosis is a serious and often life-threatening disease in immunodeficient patients. Congenital toxoplasmosis may manifest as a mild or severe neonatal disease, with onset during the first month of life or with sequelae or relapse of a previously undiagnosed infection at any time during infancy or later in life. Congenital toxoplasmosis has a wide variety of manifestations during the perinatal period.

Acute toxoplasmosis in immunocompetent persons

• Approximately 80-90% of patients are asymptomatic. Symptomatic disease may be characterized as follows:
• Patients may have cervical lymphadenopathy with discrete, usually nontender, nodes smaller than 3cm in diameter
• Fever, malaise, night sweats, and myalgias have been reported
• Patients may have a sore throat
• Retroperitoneal and mesenteric lymphadenopathy with abdominal pain may occur
• Retinochoroiditis is reported

Acute toxoplasmosis in hosts who do not have AIDS but are immunodeficient

The disease in these patients may be newly acquired or a reactivation. It may be characterized as follows:

• CNS toxoplasmosis occurs in 50% of patients - Seizure, dysequilibrium, cranial nerve deficits, altered mental status, focal neurologic deficits, headache
• Patients may have encephalitis, meningoencephalitis, or mass lesions
• Hemiparesis and seizures have been reported
• Patients may report visual changes
• They may have signs and symptoms similar to those observed in immunocompetent hosts.
• Patients may have flulike symptoms and lymphadenopathy
• Myocarditis and pneumonitis are reported.
• Toxoplasmic pneumonitis can occur - Typical symptoms of a pulmonary infection, mirroring in particular P (carinii) jiroveci, including nonproductive cough, dyspnea, chest discomfort, and fever

Symptoms associated with reactivation toxoplasmosis are dependent on the tissue or organ affected.

Clinical manifestations of toxoplasmosis in patients with AIDS

Brain involvement (ie, toxoplasmic encephalitis), with or without focal CNS lesions, is the most common manifestation of toxoplasmosis in individuals with AIDS.

Clinical findings include the following:

• Altered mental state
• Seizures
• Weakness
• Cranial nerve disturbances
• Sensory abnormalities
• Cerebellar signs
• Meningismus
• Movement disorders
• Neuropsychiatric manifestations

The characteristic presentation is usually a subacute onset, with focal neurologic abnormalities in 58-89% of cases. However, in 15-25% of cases, the clinical presentation is more abrupt, with seizures or cerebral hemorrhage. Most commonly, hemiparesis and/or speech abnormality is the major initial manifestation.

Brainstem involvement often produces cranial nerve lesions, and many patients exhibit cerebral dysfunction with disorientation, altered mental state, lethargy, and coma.

Less commonly, parkinsonism, focal dystonia, rubral tremor, hemichorea-hemiballismus, panhypopituitarism, diabetes insipidus, or syndrome of inappropriate antidiuretic hormone secretion may dominate the clinical picture.

In some patients, neuropsychiatric symptoms such as paranoid psychosis, dementia, anxiety, and agitation may be the major manifestations.

Diffuse toxoplasmic encephalitis may develop acutely and can be rapidly fatal; generalized cerebral dysfunction without focal signs is the most common manifestation, and CT scan findings are normal or reveal cerebral atrophy.

Spinal cord involvement manifests as motor or sensory disturbances of single or multiple limbs, bladder or bowel dysfunctions, or both and local pain. Patients may present with clinical findings similar to those of a spinal cord tumor. Cervical myelopathy, thoracic myelopathy, and conus medullaris syndrome have been reported.

Pulmonary toxoplasmosis (pneumonitis) due to toxoplasmosis is increasingly recognized in patients with AIDS who are not receiving appropriate anti-HIV drugs or primary prophylaxis for toxoplasmosis. The diagnosis may be confirmed by demonstrating T gondii in bronchoalveolar lavage fluid.

Pulmonary toxoplasmosis occurs mainly in patients with advanced AIDS (mean CD4⁺ count of 40 cells/µL ±75 standard deviation) and primarily manifests as a prolonged febrile illness with cough and dyspnea. Pulmonary toxoplasmosis may be clinically indistinguishable from P (carinii) jiroveci pneumonia, and the mortality rate, even when treated appropriately, may be as high as 35%.

Extrapulmonary toxoplasmosis develops in approximately 54% of persons with toxoplasmic pneumonitis.

Ocular toxoplasmosis, ie, toxoplasmic retinochoroiditis, is relatively uncommon in patients with AIDS; it commonly manifests as ocular pain and loss of visual acuity. Funduscopic examination usually demonstrates necrotizing lesions, which may be multifocal or bilateral. Overlying vitreal inflammation is often present and may be extensive. The optic nerve is involved in as many as 10% of cases.

Other, uncommon manifestations of toxoplasmosis in patients with AIDS include the following:

• Panhypopituitarism and diabetes insipidus
• Multiple organ involvement, with the disease manifesting as acute respiratory failure and hemodynamic abnormalities similar to septic shock
• Syndrome of inappropriate antidiuretic hormone secretion and possibly orchitis
• Gastrointestinal system invasion of T gondii may result in abdominal pain, diarrhea, and/or ascites (due to involvement of the stomach, peritoneum, or pancreas)
• Acute hepatic failure
• Musculoskeletal involvement
• Parkinsonism
• Focal dystonia
• Rubral tremor
• Hemichorea-hemiballismus

Congenital toxoplasmosis

This is most severe when maternal infection occurs early in pregnancy. Approximately 15-55% of congenitally infected children do not have detectable T gondii –specific IgM antibodies at birth or early infancy. Approximately 67% of patients have no signs or symptoms of infection.

Retinochoroiditis occurs in about 15% of patients, and intracranial calcifications develop in about 10%. Cerebrospinal fluid (CSF) pleocytosis and elevated protein values are present in 20% of patients.

Infected newborns have anemia, thrombocytopenia, and jaundice at birth. Microcephaly has been reported. Affected survivors may have mental retardation, seizures, visual defects, spasticity, or other severe neurologic sequelae.

Ocular toxoplasmosis

Patients develop retinochoroiditis (focal necrotizing retinitis). They have a yellowish white, elevated cotton patch with indistinct margins. The lesions may occur in small clusters. Congenital disease is usually bilateral and acquired disease is usually unilateral.

Symptoms include the following:

• Impaired vision - Either sudden or gradual, depending on the site of infection
• Blurred vision
• Scotoma
• Pain
• Photophobia
• Floaters
• Red eye
• Metamorphopsia

The acquired infection is usually subclinical and asymptomatic. In 10-20% of cases that become symptomatic, the patient develops a flulike illness characterized by fever, lymphadenopathy, malaise, myalgias, and a maculopapular skin rash that spares the palms and the soles.^[34] In individuals who are immunocompetent, the disease is benign and self-limited. Hepatosplenomegaly can also occur. Infrequently, patients develop myocarditis, polymyositis, pneumonitis, hepatitis, or encephalitis

The most common form of symptomatic acute toxoplasmosis in immunocompetent individuals is lymphadenopathy. The typical presentation is painless, firm lymphadenopathy that is confined to 1 chain of nodes, most commonly cervical.

Ophthalmologic examination reveals multiple yellow-white cottonlike patches with indistinct margins located in small clusters in the posterior pole.

A flare-up of congenitally acquired retinochoroiditis is often associated with scarred lesions juxtaposed to the fresh lesion.

Ocular toxoplasmosis (retinochoroiditis)

Symptoms of retinochoroiditis include the following^[35] :

• Decreased visual acuity - Other deficits depend on the location of the lesion
• White focal lesions with inflammation of the vitreous humor (the classic "headlight in the fog" appearance) seen on ophthalmoscopic examination
• Recurrent lesions at the border of the retinochoroidal scars

Immunocompromised individuals (AIDS CD4 count < 100 cells/microL)

Host immune function plays an important role in the pathogenicity of toxoplasmosis. Symptoms depend largely on the organ system and tissue involved and may be gradual in onset over a few weeks. They include the following:

• CNS toxoplasmosis - Seizure, mental status change, focal motor deficits, cranial nerve disturbances, sensory disturbances, cerebellar abnormalities, movement disorders, neuropsychiatric findings
• Retinochoroiditis (similar to that seen in immunocompetent individuals)
• Pneumonitis - More common in patients who have undergone bone marrow transplantation and in patients with AIDS; nonproductive cough, blood-tinged sputum, hypoxia (symptoms indistinguishable from P [carinii] jiroveci)
• Septic shock–like presentation

Multifocal, bilateral, and relentlessly progressive lesions characterize the ocular involvement. Because of their immunosuppression, these patients often have problems mounting an inflammatory reaction, which makes the formation of a retinochoroidal scar difficult. Often, the serologic diagnosis is also difficult.

Congenital toxoplasmosis

The classic clinical triad of retinochoroiditis, cerebral calcifications, and convulsions defines congenital toxoplasmosis. Other findings include the following:

• Hydrocephalus
• Microcephaly
• Organomegaly
• Jaundice
• Rash
• Fever
• Psychomotor retardation