Perinatal/Neonatal Case Presentation

Journal of Perinatology (2012) 32, 731–733. doi:10.1038/jp.2012.33

A cluster of transfusion-associated babesiosis in extremely low birthweight premature infants

P Kumar1, B C Marshall2, G deBlois3 and W C Koch2

  1. 1Division of Neonatology, Pediatrix Medical Group, CJW Medical Center, Richmond, VA, USA
  2. 2Division of Pediatric Infectious Diseases, Children's Hospital of Richmond, Virginia Commonwealth University Health System, Richmond, VA, USA
  3. 3Department of Pathology, CJW Medical Center, Richmond, VA, USA

Correspondence: Dr P Kumar, Division of Neonatology, Pediatrix Medical Group, CJW Medical Center, 7101 Jahnke Road, Richmond, VA 23225, USA. E-mail: Pankaj_kumar@pediatrix.com

Received 28 November 2011; Accepted 24 February 2012

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Abstract

Babesiosis is a parasitic infection of the red blood cells most often acquired by a tick bite. As it has also been known to be transmitted vertically and via transfusion, neonates have occasionally been reported with the infection. Here, we report a series of three premature neonates who acquired babesiosis via blood transfusion from a single donor, one of whom had difficulty clearing the infection and required multiple antimicrobials.

Keywords:

prematurity; babesia; transfusion; infants

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Introduction

Babesiosis is an intraerythrocytic protozoal infection caused by B. microti species commonly acquired from a tick bite in the Northeastern United States.1 Symptoms of Babesiosis range from asymptomatic infection to fever, hemolytic anemia, thrombocytopenia and hyperbilirubinemia. Mortality may be as high as 5–9 % in hospitalized patients who are elderly, immunocompromised or asplenic.2 Babesiosis may also be transmitted by transfusion of blood products and rarely transplacentally.3, 4, 5, 6 The cases of neonates with transfusion-associated infections have been reported7, 8, 9, 10, 11, 12 primarily in areas endemic for babesiosis. Here, we report a series of three cases of transfusion-associated babesiosis in preterm infants hospitalized in a non-endemic region for Babesia who had a protracted course and therapy, well beyond prior published recommendations and reported clinical experience.

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Case 1

The index patient was an extremely premature former 23-week gestation female weighing 452g at birth with severe respiratory distress syndrome. Her clinical course was complicated by surgical ligation of PDA on day of life (DOL) 21, chronic lung disease, candidal blood stream infection on DOL 25 and Staphylococcus epidermidis bacteremia on DOL 50. The infant had TPN-induced cholestasis and received multiple blood transfusions for anemia. While investigating worsening of hemolytic anemia, thrombocytopenia and direct hyperbilirubinemia, a peripheral smear revealed intraerythrocytic parasites in ‘ring forms’ resembling Plasmodium species (Figure 1). On the basis of the recommendations of an infectious diseases consultant, intravenous clindamycin and quinidine were initiated in the recommended neonatal doses.13 At the time of diagnosis, the infant was 141 days old, afebrile and had mild hepatosplenomegaly. Review of prenatal history with her mother revealed no history of maternal illness, travel or tick bite.

Figure 1.
Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

High power giemsa-stained peripheral smear from Case 2, demonstrating multiple ring forms of B.microti.

Full figure and legend (102K)

The blood specimens were sent for review to Division of Consolidated Laboratory Services (DCLS, Virginia) and subsequently to the Centers for Disease Control and Prevention for confirmation of the diagnosis of B. microti by serology and PCR. The hospital blood bank and Virginia Department of Health were contacted to investigate the presumed transfusion-acquired infection.

As the infant continued to be parasitemic at the end of a 2-week course of therapy, oral azithromycin and atovaquone were added on the 15th day of treatment; parasitemia cleared after a total duration of 21 days. The child subsequently developed severe necrotizing enterocolitis and expired. There was no parasitemia at the time of death.

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Case 2

A former 24-week gestation Hispanic female weighing 625g at birth with a NICU course complicated by respiratory distress syndrome and subsequent chronic lung disease, prolonged TPN and multiple transfusions for anemia developed fever, thrombocytopenia and mild hepatosplenomegaly. She progressed to respiratory failure requiring conventional and ultimately high frequency ventilation. Babesiosis was diagnosed by peripheral smear in this patient on DOL 71 during a laboratory-initiated review of all infants in the NICU who had received blood from the same donor unit as that of the index case (Case 1); she was started on IV quinidine and clindamycin.

This infant had received two transfusions from the same donor unit of blood and demonstrated 17% parasitemia (Table 1), direct hyperbilirubinemia and severe refractory thrombocytopenia (18 × 109/l).


This infant required four antiparasitic drugs to clear parasitemia. One month after the first negative smear, thrombocytopenia recurred. Smear review confirmed Babesia reinfection. Peak parasitemia during this recurrent illness was 3.5%. Therapy with all four antiparasitic agents was reinitiated and negative smears were not noted until the 12th day of four drug therapy.

The infant later developed severe ventilator-dependent chronic lung disease requiring tracheostomy and pulmonary hypertension for which she was treated with inhaled nitric oxide, sildenafil and steroids, but ultimately died. No parasitemia was observed at the time of death.

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Case 3

This patient was a thriving former 26-week gestation premature female weighing 578g at birth with clinical course complicated by respiratory distress syndrome, PDA ligation at 5 weeks and necrotizing enterocolitis, which improved with conservative therapy. On DOL 138, the laboratory reported intraerythrocytic Babesia while reviewing all NICU patients who had received blood from the same contaminated donor unit. The child had mild anemia without other clinical or laboratory abnormalities. The infant was treated with four antiparasitic medications for complete resolution. The child had an otherwise uncomplicated course was discharged home uneventfully and doing well at the time of this report.

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Discussion

Babesiosis is uncommon in the neonatal population. Only 18 cases have been reported to date in the English medical literature. In all, 12 neonatal cases 8, 9, 10, 11, 12 of transfusion-acquired babesiosis have been reported since the first case description by Wittner et al. in 1982.7

Premature and critically ill neonates requiring multiple packed red cells transfusions are at an increased risk for this illness. Additionally, the policy of aliquoting blood from one unit to multiple infants increases vulnerability to acquiring infections from a single contaminated unit.

The three cases described in this report received irradiated, packed red cell aliquots from the same unit of blood. Blood from all three patients and the archived segment from the donor unit tested positive for B. microti by PCR and by serology. The donor was from Virginia, asymptomatic at the time of blood donation and had no history of a tick bite; the only travel history was a trip to Connecticut several weeks before donation.14

B. microti has been described as the second most common transfusion-transmitted parasitic infection after Plasmodium.15 Routine screening of donor blood for Babesiosis is not performed in the United States because of the cost, complexity of definitive tests and lack of FDA licensed test for screening.

The initial diagnosis of the index case was serendipitous; ring forms resembling malaria discovered on the peripheral smear of Case 1 led to further testing and the diagnosis of babesiosis in all three infants. Babesiosis was not suspected at the outset given the location of these cases in a nonendemic area.

Of the previously reported cases of transfusion-acquired babesiosis in neonates, the highest reported parasitemia was 17 %,11 equivalent to that of Case 2 in our case series. Case 2 received two transfusions of blood from this donor, suggesting this infant's increased parasite load and severity of illness may have been dose-related. Exchange transfusion2 was considered, but not performed, given the infant's clinical instability.

The recommended first-line therapy for children with babesiosis is a combination of oral quinine (30mgkg−1 per day divided every 8h) and clindamycin (20 to 40mgkg−1 per day divided every 8h) for 7 to 10 days.13 Intravenous quinidine may be used instead of quinine in patients too ill or otherwise unable to tolerate oral medication.1 An alternative regimen of atovaquone and azithromycin has more recently been found to be equally efficacious in adults,16 with fewer adverse effects. Although the efficacy of azithromycin and atovoquone has not been studied in children, several cases of neonates4, 6, 9, 11 and older infants17 successfully treated with this combination have been reported.

For the neonates in our series, parasitemia persisted even after more than 10 days of first-line antimicrobials necessitating the addition of azithromycin and atovaquone. No documented resistance of Babesia to quinidine and clindamycin has been reported. Difficulty in eradicating this infection in premature neonates could reflect their relatively compromised immune system and impaired splenic function.18 Literature suggests that patients should be treated for 6 weeks, or at least 2 weeks after a negative peripheral smear.19

The purpose of this case series is to alert clinicians to the possibility of this otherwise uncommon infection that may prove fatal if unrecognized and untreated. Regardless of geographic location, neonatologists should consider babesiosis in the differential diagnosis of neonates with history of blood transfusions who develop fever, hemolytic anemia, thrombocytopenia and hyperbilirubinemia. Premature infants with immature immune responses may require prolonged therapy for babesial infection, and monitoring for recurrence should be considered.

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Conflict of interest

The authors declare no conflict of interest.

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References

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Acknowledgments

The authors would like to acknowledge Jean Garrett of the CJW Hospital Clinical Laboratory and Mary Mismas of the DCLS for their technical assistance with evaluation of numerous blood specimens for parasitemia. We would also like to acknowledge the assistance of Barbara Herwaldt and other members of the CDC Division of Parasitic Diseases for their review and confirmation of parasitemia in these infants.