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Introduction

Background

Toxoplasma gondii is a widely distributed protozoan that usually causes an asymptomatic infection in the healthy host.¹ Toxoplasmosis refers to a symptomatic infection by T gondii and can be acute or chronic. Apart from disease in immunocompromised individuals, congenital toxoplasmosis is the most serious manifestation of infection, resulting from vertical transmission of T gondii from a parasitemic mother to her offspring. The severity of disease depends on the gestational age at transmission. Ophthalmologic and neurologic disabilities are the most important consequences of infection and can be present even when the congenital infection is asymptomatic. Congenital toxoplasmosis is a preventable disease. Prepregnancy screening accompanied by serial titers and appropriate counseling in women with initial negative titers may minimize cases.²

Pathophysiology

T gondii is an obligate intracellular protozoan. It has an intestinal and an extraintestinal cycle in cats but only an extraintestinal cycle in other hosts, including herbivores, omnivores, and carnivores.

T gondii exists in 3 forms, as follows:

• Bradyzoites are slowly multiplying organisms contained in tissue cysts, usually localized to muscle (skeletal and cardiac) and brain. They live in their host cells for months to years. Once ingested, gastric enzymes degrade the cyst wall, liberating viable bradyzoites.
• Tachyzoites are rapidly dividing organisms found in tissues during the acute phase of infection. The tachyzoites are the forms responsible for tissue destruction. Multiplication continues until either cyst formation or host cell destruction occurs. After cell death, the free tachyzoites invade other cells and resume rapid multiplication.
• Sporozoites (oocysts) result from the parasite's sexual cycle, which takes place in the epithelial cells of the cat intestine. When eliminated by the cat, these cysts must first undergo sporulation to become infectious, a process that takes 2-3 days in temperate climates and longer in cold climates. Therefore, the risk of infection is minimized if cat litter boxes are cleaned daily. Cats shed 1-100 million oocysts after the first infection, but, because of immunity, reinfection is rarely followed by reshedding of oocysts. Passive antibody transference to newborn kittens does not prevent shedding of oocysts.

Human horizontal infection occurs from ingesting food contaminated with oocysts or poorly cooked food containing tissue cysts (bradyzoites). Although experimental attempts to transmit tachyzoites by arthropods were negative, cockroaches and flies are believed to be able to transport oocysts to water and food. Because parasitemia can persist up to a year in healthy persons, blood transfusion is a potential source of infection. Once the individual is infected, the organism persists as tissue cysts for life. The degree of organ involvement varies considerably among patients but mostly depends on the immune status of the host. Fetuses and immunocompromised patients are most severely affected.

Vertical transmission is the cause of congenital toxoplasmosis. The infection can occur in utero or during a vaginal delivery. Transmission by breastfeeding has not been demonstrated. In general, only primary infection during pregnancy results in congenital toxoplasmosis. Thus, it is exceedingly rare for a woman to deliver a second child with congenital toxoplasmosis unless she is immunocompromised, usually from acquired immunodeficiency syndrome (AIDS).³ Infections that occur before but within 6 months of conception may result in transplacental transmission. Intrauterine exposure can result in an uninfected infant or infection that ranges from being asymptomatic to causing stillbirth. Approximately 30% of exposed fetuses acquire the infection, but most of the infants are asymptomatic. The severity of infection in the fetus depends on the gestational age at the time of transmission.

In general, earlier infection is more severe but less frequent. As a consequence, 85% of live infants with congenital infection appear normal at birth. Very early infections (ie, occurring in the first trimester) may result in fetal death in utero or in a newborn with severe CNS involvement, such as cerebral calcifications and hydrocephalus.

Frequency

United States

The frequency of congenital toxoplasmosis depends on the incidence of primary infection in women of childbearing age. The earlier a woman acquires a primary infection, the less likely she is to transmit the parasite to her offspring. Prevalence increases with age. In New York, antibody prevalence was 16% in women aged 15-19 years, 27% in women aged 20-24 years, 33% in women aged 25-29 years, 40% in women aged 30-34 years, and 50% in women older than 35 years. Rates in women of childbearing age in Palo Alto, California, dropped from 27% in 1964 to 10% in 1987. Other areas in the United States report positive antibody titers of 30% in women of childbearing age in Birmingham (1983), 12% in Chicago (1987), 14% in Massachusetts (1998), 3.3% in Denver (1986), 30% in Los Angeles (1993), 12% in Texas (1993), and 13% in New Hampshire (1998).

The prevalence of congenital infection can be indirectly estimated from the incidence rate of primary infection during pregnancy by multiplying the number of mothers who acquire infection during pregnancy by the transmission rate of the parasite to the fetus. On the basis of data from the National Health and Nutrition Examination Survey during 1989-1994, the incidence of primary infection for seronegative pregnant women was 0.27%. With 4 million births per year and an overall transmission rate of 33%, approximately 3500 infected children are born in the United States every year.⁴ The rate likely varies by region.

Direct estimates of congenital infection may be derived by measuring anti-Toxoplasma immunoglobulin (Ig)M in newborn sera. However, this may underestimate the true incidence because infants with toxoplasmosis may not have demonstrable IgM in up to 20% of cases. In Alabama, the incidence was 0.1 per 1000 births. Health care workers in Massachusetts began screening sera of newborns in 1986. From 1986-1998, a total of 99 cases were detected (incidence of 1 in 10,000 births) in Massachusetts, but at least 6 cases were missed by the screening.

International

Worldwide, the reported incidence of congenital toxoplasmosis is decreasing. The prevalence of positive antibody titers among pregnant women is often higher outside the United States. The rate of positive antibody titers is 81% in the Central African Republic, 48% in Tanzania, 23% in Zambia, 53-58% in Argentina, 36% in Austria, 46% in Belgium, 59% in Chile, 60% in Colombia, more than 75% in Ethiopia, 52% in France, and 46% in Guatemala. The estimated incidence of congenital toxoplasmosis is 6 per 1000 births in France, 2 per 1000 births in Poland, 7-10 per 1000 births in Colombia, and 3 per 1000 births in Slovenia.

Mortality/Morbidity

Fetuses and immunocompromised individuals are at particularly high risk for severe sequelae and even death. Infection acquired postnatally is usually much less severe.

• Newborns with acute congenital toxoplasmosis often die in the first month of life.
• Subacute congenital disease may not be observed until some time after birth, when symptoms start to appear.

Race

The incidence of disease depends on sanitary conditions and culinary habits. The ingestion of raw or poorly cooked meat increases the risk of toxoplasmosis. Individuals with poor sanitary conditions and those who eat raw or poorly cooked meat are at an increased risk of acquiring Toxoplasma infection, unrelated to race.

Sex

Incidence does not significantly vary between the sexes.

Age

Incidence of T gondii antibodies increases with increasing age. The seroconversion rate in women of childbearing age is 0.8% per year. The risk of transplacental transmission is greatest during the third trimester of pregnancy.

Clinical

History

Pediatric toxoplasmosis can be acute or chronic, asymptomatic or symptomatic, and congenital or postnatally acquired.

• Congenital toxoplasmosis is the consequence of transplacental hematogenous fetal infection by T gondii during primary infection in pregnant women. Primary infection in an otherwise healthy pregnant woman is asymptomatic in 60% of cases. Symptoms during pregnancy are frequently mild. The most common manifestations are fatigue, malaise, a low-grade fever, lymphadenopathy, and myalgias. Latent Toxoplasma infection with reactivation during pregnancy may lead to congenital infection only in immunocompromised women (most commonly, those with AIDS).
• The classic triad of chorioretinitis, hydrocephalus, and intracranial calcifications cannot be used as a strict diagnostic criterion for congenital toxoplasmosis because a large number of cases would be missed. Congenital toxoplasmosis may occur in the following forms:
  • Neonatal disease
  • Disease occurring in the first months of life
  • Sequelae or relapse of previously undiagnosed infection
  • Subclinical infection
• When clinically recognized in the neonate, congenital toxoplasmosis is very severe. Signs of generalized infection are usually present, such as intrauterine growth retardation, jaundice, hepatomegaly, splenomegaly, lymphadenopathy, and a rash. Neurologic signs are severe and always present. They include microcephaly or macrocephaly, bulging fontanelle, nystagmus, abnormal muscle tone, seizures, and delay of developmental milestone acquisition.
  • Most cases of chorioretinitis result from congenital infection, although patients are often asymptomatic until later in life. Symptoms include blurred vision, scotoma, pain, photophobia, and epiphora. Impairment of central vision occurs when the macula is involved, but vision may improve as inflammation resolves. Relapses of chorioretinitis are frequent but rarely accompanied by systemic signs or symptoms.
  • Latent toxoplasmosis may reactivate in women with human immunodeficiency virus (HIV) and result in congenital transmission. Congenital toxoplasmosis in the infant with HIV appears to run a more rapid course than in infants without HIV.

Physical

• Lymphadenopathy is the most common form of symptomatic acute toxoplasmosis in immunocompetent individuals.
• Patients typically present with painless firm lymphadenopathy that is confined to one chain of nodes, which are most commonly cervical. The suboccipital, supraclavicular, axillary, and inguinal groups may also be involved.
• Other physical manifestations include a low-grade fever, occasional hepatosplenomegaly, and a rash.
• Ophthalmologic examination reveals multiple yellow-white cottonlike patches with indistinct margins located in small clusters in the posterior pole.
• Characteristically, a focal necrotizing retinitis develops that may atrophy and generate black pigment, or it may be associated with panuveitis. Papillitis is usually indicative of CNS disease. Flare-up of congenitally acquired chorioretinitis is often associated with scarred lesions in proximity to the fresh lesions.
• Because of multifocal involvement of the CNS, clinical findings widely vary. They include alterations in mental status, seizures, motor weakness, cranial nerve disorders, sensory abnormalities, cerebellar signs, meningismus, movement disorders, and neuropsychiatric manifestations in patients with immunocompromise.

Causes

• The etiologic agent is T gondii.
  • Congenital disease is passed transplacentally from the newly infected mother to the fetus during pregnancy.
  • Other syndromes may result from newly acquired infection or reactivation of latent infection.
  • Ingestion of meat or foods containing cysts or oocysts present in cat feces can cause infection.
  • Infection can be transmitted by blood transfusion or organ transplantation.
• Hosts who are immunocompromised, especially those with defects in cellular immunity such as AIDS, are also at increased risk for severe disease.

Source : http://emedicine.medscape.com/article/1000028-overview