Clinical Information

Toxoplasma gondii:

Toxoplasma gondii is an obligate intracellular protozoan parasite that is capable of infecting a variety of intermediate hosts including humans. Infected definitive hosts (cats) shed oocysts in feces that rapidly mature in the soil and become infectious.(1) Toxoplasmosis is acquired by humans through ingestion of food or water contaminated with cat feces or through eating undercooked meat containing viable oocysts. Vertical transmission of the parasite through the placenta can also occur, leading to congenital Toxoplasmosis. Following primary infection, Toxoplasma gondii can remain latent for the life of the host; the risk for reactivation is highest among immunosuppressed individuals.

Seroprevalence studies performed in the United States indicate that approximately 9% to 11% of individuals between the ages of 6 and 49 have antibodies to Toxoplasma gondii.(2) Infection of immunocompetent adults is typically asymptomatic. In symptomatic cases, patients most commonly present with lymphadenopathy and other nonspecific constitutional symptoms, making definitive diagnosis difficult to determine.

Severe-to-fatal infections can occur among patients with AIDS or individuals that are otherwise immunosuppressed. These infections are thought to be caused by reactivation of latent infections and commonly involved the central nervous system.(3)

Transplacental transmission of the parasites resulting in congenital toxoplasmosis can occur during the acute phase of acquired maternal infection. The risk of fetal infection is a function of the time at which acute maternal infection occurs during gestation.(4) The incidence of congenital toxoplasmosis increases as pregnancy progresses; conversely, the severity of congenital toxoplasmosis is greatest when maternal infection is acquired early during pregnancy. A majority of infants infected in utero are asymptomatic at birth, particularly if maternal infection occurs during the third trimester, with sequelae appearing later in life. Congenital toxoplasmosis results in severe generalized or neurologic disease in about 20% to 30% of the infants infected in utero; approximately 10% exhibit ocular involvement only and the remainder are asymptomatic at birth. Subclinical infection may result in premature delivery and subsequent neurologic, intellectual and audiologic defects.

Rubella:

Rubella (German or 3-day measles) is a member of the togavirus family and humans remain the only natural host for this virus. Transmission is typically through inhalation of infectious aerosolized respiratory droplets and the incubation period following exposure can range from 12 to 23 days.(5) Infection is generally mild and self-limited, and is characterized by a maculopapular rash beginning on the face and spreading to the trunk and extremities, fever, malaise, and lymphadenopathy.(6)

Primary, in utero rubella infections can lead to severe sequelae for the fetus, particularly if infection occurs within the first 4 months of gestation. Congenital rubella syndrome is often associated with hearing loss, cardiovascular and ocular defects.(7)

The United States 2-dose measles, mumps, rubella (MMR) vaccination program, which calls for vaccination of all children, leads to seroconversion in 95% of children following the first dose.(5) A total of 4 cases of rubella were reported to the CDC in 2011 without any cases of congenital rubella syndrome.(8) Due to the success of the national vaccination program, rubella is no longer considered endemic in the United States (cdc.gov/rubella). Immunity may however wane with age as approximately 80% to 90% of adults will show serologic evidence of immunity to rubella.

Cytomegalovirus (CMV):

CMV is a member of the Herpesviridae family of viruses and usually causes asymptomatic infection after which it remains latent in patients, primarily within bone marrow derived cells.(9) Primary CMV infection in immunocompetent individuals may also manifest as a mononucleosis-type syndrome, similar to primary Epstein-Barr virus infection, with fever, malaise, and lymphadenopathy.

CMV is a significant cause of morbidity and mortality among bone marrow or solid organ transplant recipients, individuals with AIDS and other immunosuppressed patients due to virus reactivation, or from a newly acquired infection.(10,11) Infection in these patient populations can affect almost any organ and lead to multi-organ failure. CMV is also responsible for congenital disease among newborns and is 1 of the ToRCH infections (toxoplasmosis, other infections including syphilis, rubella, CMV, and herpes simplex virus [HSV]).

CMV seroprevalence increases with age. In the United States the prevalence of CMV-specific antibodies increases from approximately 36% to over 91% in adolescents between the ages of 6 and 11 and adults over 80 years old, respectively.(12)

Herpes Simplex Virus (HSV) Types 1 and 2:

HSV types 1 and 2 are members of the Herpesviridae, and produce infections that may range from mild stomatitis to disseminated and fatal disease. Clinical conditions associated with HSV infection include gingivostomatitis, keratitis, encephalitis, vesicular skin eruptions, aseptic meningitis, neonatal herpes, genital tract infections, and disseminated primary infection.

Infections with HSV types 1 and 2 can differ significantly in their clinical manifestations and severity. HSV type 2 primarily causes urogenital infections and is found almost exclusively in adults. HSV type 1 is closely associated with orolabial infection, although genital infection with this virus can be common in certain populations.

The diagnosis HSV infections is routinely made based on clinical findings and supported by laboratory testing using PCR or viral culture. However, in instances of subclinical or unrecognized HSV infection, serologic testing for IgG-class antibodies to type-specific HSV glycoprotein G (gG) may be useful. There are several circumstances in which it may be important to distinguish between infection caused by HSV types 1 and 2.(13) For example, the risk for reactivation is highest for HSV type 2 and the method of antiviral therapy may be different depending on the specific type of HSV causing disease. In addition, the results of HSV type specific IgG testing is sometimes used during pregnancy to identify risks of congenital HSV disease and allow for focused counseling prior to delivery.(14,15)