Probable Congenital Babesiosis in Infant, New Jersey, USA

Only 2 neonates with transplacentally or perinatally acquired (congenital) babesiosis have been reported. We describe a probable third congenital case of babesiosis in a 26-day-old infant; transmission was determined on the basis of a blood smear from the infant (15% parasitemia) and serologic results from the infant and mother.


The Case
A 26-day-old, 8-pound, full-term infant girl was transferred to Saint Peter's University Hospital for evaluation of fever and hyperbilirubinemia. For 1 week, she was not feeding well and was gagging and irritable. On the day of admission, her mother noted fever and yellow eyes. The mother (a migrant crop worker) reported having had an un-eventful pregnancy, labor, and delivery, except for having been bitten by 2 ticks at 8 months' gestation while picking crops in New Jersey. She did not seek treatment. The mother had not traveled elsewhere in the United States during her pregnancy. Knowledge about earlier travel to Babesiaendemic areas would have been helpful in understanding the mother's infection, but this information was unavailable. The infant had no history of tick exposure; she had been outdoors only for visits to the pediatrician. Physical examination showed an alert but pale infant weighing 4.4 kg; her temperature was 101.8°F (38.7°C), pulse rate 160/min, respiratory rate 36/min, blood pressure 90/40 mm Hg, and oxygen saturation 99% while breathing room air. Her conjunctivae were icteric. Her liver and spleen were palpable 4 cm and 5 cm below their respective costal margins. No hemorrhagic lesions or tick bites were noted. The rest of her physical examination fi ndings were unremarkable except for a diaper rash.
Subsequently, the infant's lactate dehydrogenase concentration was found to be 1,912 IU/L (reference range 313-618 IU/L) and later rose to 2,535 IU/L ( Table 1). The infant's Babesia immunoglobulin (Ig) G and IgM titers by immunofl uorescent antibody (IFA), which are genus specifi c but not species specifi c, were 256 (reference <16) and 40 (reference <20), respectively (both tests were performed by Quest Diagnostics-Nichols Institute, Chantilly, VA, USA). Lyme IgG Western blot plus 2 Lyme IgM Western blots, performed early during hospitalization and just before discharge, were negative. The mother's peripheral blood smear did not show any parasites, but her Babesia IgG and IgM titers by IFA were >1,024 and 80, respectively, and her Lyme serology was positive. The mother refused additional testing. Despite the variability in sensitivity and specifi city of commercially available serologic tests (particularly the IFA for Babesia IgM), Babesia serologic results were not confi rmed at a reference laboratory. Species-specifi c PCR was not performed.
After concluding that this infant had probable congenital babesiosis, we began treating her with oral atova- quone (40 mg/kg/d) in 2 divided doses and azithromycin (12 mg/kg/d) once per day. The infant received 1 transfusion with packed red blood cells on hospital day 3 because of continued hemolysis, but she did not require exchange transfusion despite having a high initial parasite count. The infant's parasitemia decreased rapidly, and she responded well to treatment (Table 1). She was discharged after 8 days and was to complete a 10-day course of atovaquone and azithromycin (which were well tolerated); she was subsequently lost to follow-up.

Conclusions
Of 10 cases of babesiosis in neonates that have been reviewed (5), 2 were congenital (3,4), 2 were transmitted by a tick bite (6), and 6 were associated with transfusions (5,7-9). The 2 congenital cases (3,4) are compared to our probable congenital case ( Table 2). All 10 of the affected neonates were reported to have <9% parasitemia (5). The illness ranged from no symptoms in 2 infants transfused with contaminated blood (8) to symptomatic disease (as in our infant) with fever and hepatosplenomegaly in 5 of 7 (71%), hemolytic anemia in 8 of 10 (80%), indirect hyperbilirubinemia in 4 of 5 (80%), and thrombocytopenia in 7 of 9 (78%) (5). Five of 8 (63%) patients required erythrocyte transfusion (5). The infant we describe had all of these manifestations as well as a higher parasite count than described previously (5). Clearly, the spectrum of neonatal babesiosis is variable and must be more fully elucidated, as must determinants of the illness's clinical course and parasite clearance. In neonates, the degree of parasitemia may not parallel the severity of the babesiosis.
The combination of quinine sulfate and clindamycin hydrochloride for treatment of a newborn with transfusionassociated babesiosis was described in 1982 and subsequently became the fi rst accepted treatment (7). A combination of azithromycin with atovaquone for 7 to 10 days has emerged as an alternative regimen (8,10-11), having been used successfully in 2 neonates (8,10) and several adults (11) in whom it appears to be safe and effective. Finally, the addition of azithromycin or atovaquone to the clindamycin hydrochloride plus quinine sulfate regimen has been proposed (2,8), particularly if parasitemia is slow to resolve.
Recently, our understanding of babesiosis and the methods of testing for it have improved dramatically. Because babesiosis (and congenital babesiosis) is an emerging tick-borne zoonosis, it is worthwhile to review the state-ofthe-art approach to its diagnosis in the context of the limitations to diagnosis inherent in this particular case, including its retrospective nature, the mother's lack of insurance and resultant unwillingness to undergo any additional laboratory testing, and the loss to follow-up of the infant and her migrant family. Diagnosis of congenital babesiosis requires defi nitive evidence of babesiosis, including evidence from reference laboratory species-specifi c IFA testing, PCR confi rmation, and evidence from reference laboratory evaluation of peripheral blood smears, particularly blood smears with high parasitemia (necessary because of the numerous species of Babesia endemic to the United States, including B. microti, B. divergens-like, B. duncani, MO-1, CA-1, and WA-1). Accurate diagnosis also requires collection of extensive epidemiologic information about patients with suspected infections, including their recent and remote travel history, exposure to ticks, transfusion or transplant. Follow-up for recrudescence is important, particularly for the immunocompromised patient. Our report of a probable third case of congenital babesiosis illustrates the variability in the manifestations and clinical course of the illness, suggesting a need for improvement in how the dis-ease is recognized and for evaluation of current treatment modalities.