Neonatal hepatitis with toxoplasmosis.

Congenital toxoplasmosis may be subclinical, or may present with multisystem involvement. Most of the symptomatic cases have either ocular or neurological manifestations. A case of congenital toxoplasmosis presenting as isolated hepatitis is reported.

INTRODUCTION

Congenital toxoplasmosis is caused by transplacental acquisition of the intracellular protozoan Toxoplasma gondii, and has an incidence of 1/10,000 to 80/10,000 births.[1] Worldwide, about 0.5-1% of pregnant women become contaminated by T. gondii.[2] Diagnosis may be made prenatally by detection of the parasite in fetal blood or amniotic fluid or from the placenta, cord or infant′s peripheral blood using mouse inoculation or a polymerase chain reaction (PCR) of its genomic material. Serologic diagnosis can be made by IgM or IgA or persistence (over 12 months) of IgG anti-toxoplasma antibody determined in the infant blood.[3]

Maternal infection with the intracellular protozoan parasite is usually acquired by contact with the oocytes excreted in cat feces or ingestion of inadequately cooked meat. The infectious agent crosses the placenta best during the third trimester.[3] However, those infected earlier in pregnancy have more severe disease. A majority of the recorded cases of congenital toxoplasmosis have shown either clinical evidence of damage to the central nervous system at birth or have developed such signs after the first few weeks of life. Most infants with congenital toxoplasmosis have hepatosplenomegaly, but jaundice may be variable. Presentation as isolated neonatal hepatitis has not been reported earlier. We present a child with neonatal hepatitis and congenital toxoplasmosis.

CASE REPORT

A 2-month-old girl born of nonconsanguineous marriage, 2nd of twins, was referred for incidentally detected jaundice. The first twin had neonatal cholestasis with increased galactose and lactose on urine organic acids and had died subsequently. Both babies were small in size at birth as per the mother (exact birth weight is not known). The mother had no fever or rash during pregnancy and there was no exposure to animals. On examination, the child had hepatosplenomegaly with jaundice, while the other systems were normal. Investigations showed hemoglobin of 10.1 gm%, WBC count of 16,800/cumm and platelets were adequate on smear. Bilirubin was 5.1 mg/dL (normal <1.2 mg/dL), with direct bilirubin of 2.5 mg/dL, SGOT=144 IU/L (normal=5-40 IU/L), SGPT=88 IU/L (normal=5-25 IU/L), alkaline phosphatase of 3050 IU/L (normal <650 IU/L), GGTP of 27 IU/L (normal), total proteins of 7.4 gm/dL and albumin of 3.5 gm/dL. Prothrombin time and partial thromboplastin time were normal. Urine reducing substance was negative and ultrasound abdomen showed hepatosplenomegaly and presence of gall bladder. Hepatobiliary iminodiacetic acid scan (HIDA) scan was normal. Toxoplasmosis, other (syphilis), rubella, cytomegalovirus and herpes (TORCH) titres showed positive Toxoplasma IgG (40 IU/mL, negative <10 IU/mL), cytomegalovirus IgG (40 IU/mL, negative <10 IU/mL) and rubella IgG (75 IU/L, negative <10 IU/mL). On repeating the TORCH titres after 3 weeks, Toxoplasma IgG was 60 IU/mL and Toxoplasma IgM was also positive. Parents were advised regarding testing for galactosemia and PCR for Toxoplasma and CMV, but they could not afford the same. (Testing for galactosemia costs Rs 2250, PCR for Toxoplasma is not available in India and CMV PCR test costs Rs 4000.) Ultrasound of the skull showed mild prominence of both lateral ventricles. No other neuroimaging tests were done due to nonaffordability. Cerebrospinal fluid examination was not done and neurological examination was normal. The child was started on Sulphadoxine (20 mg/kg/day) and Pyrimethamine (1 mg/kg/day), and this was given for 1 year. The child had normal achievement of milestones during the year and jaundice resolved by 5 months of age. At the end of 1 year, her weight was 6.5 kg, she had mild hepatomegaly on ultrasound and examination, head circumference was 42.2 cm, length was 70 cm and hemogram and liver function tests as well as ultrasound of skull were normal. Her hearing and ophthalmology examination was also normal.

DISCUSSION

It has been estimated that 15-17% of maternal Toxoplasma infections acquired between the 7th and 14th weeks of gestation are transmitted to the embryo.[4] Infection in the first trimester usually results in abortion or still birth. If the neonates survive, they present with cerebral symptoms of convulsions, tremors, paralysis, impaired intellect and behavioral problems.[5] Cases with signs of generalized disease at birth have been described.[67] Manifestations may include prematurity, intrauterine growth restriction, jaundice, hepatosplenomegaly, myocarditis, pneumonitis and skin rash. In a study of clinical presentation of 43 children with congenital toxoplasmosis, chorioretinitis was observed in 95% of the cases and neurological sequelae in 54%.[8] Congenital or neonatal toxoplasmosis should be strongly suspected when there are characteristic ocular lesions and the presence of cerebral calcifications in radiological examinations. Focal areas of necrosis may be seen in the viscera, leading to myocarditis and pneumonitis and, rarely, hepatitis. Callahan et al. remarked that there is, in most cases, no satisfactory explanation of jaundice occurring in congenital toxoplasmosis.[9] In the liver, toxoplasmic granulomas have not been found and free parasites are noted only on very rare occasions, the main features being foci of erythropoiesis, hemosiderosis, inspissations of bile within the canaliculi and, occasionally, a mononuclear periportal reaction. Sabin suggested that the jaundice might be due to a direct toxic effect of Toxoplasma on the liver cells.[10] In any case, isolated hepatitis is uncommon, but may be the only indicator of infection,[11] as seen in our case. In our patient though, we could not demonstrate Toxoplasma in the liver tissue, while rising Toxoplasma IgG titer was suggestive of infection and treatment led to resolution of hepatitis.

Thus, while determining the cause of neonatal hepatitis, congenital toxoplasmosis should be considered as a possibility, even when the accompanying constellation of symptoms is absent, and benefit of therapy should be given on confirmation of diagnosis.