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An Infant Presenting With Fever and Thrombocytopenia

Reynolds, Meghan E. MD; Murray, Robert G.P. MD; House, Samantha A. DO, MPH

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The Pediatric Infectious Disease Journal: August 2020 - Volume 39 - Issue 8 - p 771-773
doi: 10.1097/INF.0000000000002780
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CASE

A 40-day-old term female infant presented to the emergency department at a tertiary, academic, rural medical center in Northern New England with 1 day of increased fussiness and fever up to 39.4°C. She was born full term via an uncomplicated spontaneous vaginal delivery to a group B strep-negative mother. She had been exclusively breast-fed since birth, was growing well and was meeting developmental milestones. There were no known sick contacts. Her past medical history was significant for a neck mass that developed at 2 weeks of life for which she had been referred to otolaryngology and was awaiting outpatient evaluation. She was the only child of parents living on a turkey farm. The infant had not spent significant time outdoors and had no direct contact with any farm animals. Her father travelled for work and had been to East Asia 6 months before her presentation.

Initial evaluation revealed a well-appearing infant; however, she was febrile to 38.4°C and had a heart rate of 188 beats per minute, respiratory rate of 48 breaths per minute and blood pressure of 90/64 mm Hg. On examination, she had a flat anterior fontanelle, no congestion or rhinorrhea and clear breath sounds. She was noted to have a 2-cm firm, mobile mass palpable in her neck that was not warm, erythematous or tender to touch. Cardiac examination revealed normal heart sounds and no murmur; abdominal examination was normal without masses or organomegaly. Her skin revealed diffuse laciness and scattered petechiae on her extremities, chest and back. Neurologic examination was reassuring with appropriate alertness, good tone and normal newborn reflexes.

A sepsis evaluation was initiated per our hospital’s febrile infant protocol including a complete blood count (CBC), blood culture, urinalysis and urine culture. Consideration was made for lumbar puncture; however, given age >28 days and well appearance, the decision was made to defer in favor of clinical observation. Antibiotics were also initially deferred, given the well clinical appearance of this infant.

Otolaryngology was consulted to evaluate her neck mass. At the time of presentation, it was unclear whether the neck mass was related to this acute illness given that it had been present well before the onset of fever. An ultrasound of this mass was obtained in the emergency department that was consistent with a diagnosis of fibromatosis colli, a benign neck mass in newborns that typically self-resolves with physical therapy by 1 year of age and was determined to be unrelated to current presentation.

Initial laboratory studies revealed a normal urinalysis and normal electrolytes. CBC was notable for mild anemia with a hemoglobin of 10.3 g/dL, thrombocytopenia with a platelet count of 41,000/mm3, white blood cell count of 7500/mm3 and an absolute neutrophil count of 1070/mm3. Subsequent review of the peripheral smear helped confirm the diagnosis.

For Denouement see P. 772.

DENOUEMENT

Continued from P. 771.

Abnormal red blood cell morphology on the initial complete blood count (CBC) triggered a peripheral smear, and shortly after her admission to the hospital, her care team was notified that this smear revealed intracellular red blood cell inclusions. On manual review of the sample, these inclusions were consistent with the finding deemed a “Maltese cross,” which is pathognomonic for babesiosis. Parasite burden was estimated at 3.55%, with severe infection usually seen at a parasitemia of >4%.1 A polymerase chain reaction (PCR) test confirmed the diagnosis of babesiosis.

The infant had no notable outdoor exposure or prior transfusion history and therefore vertical transmission from her mother was hypothesized to be the most likely etiology for her infection. Maternal laboratory studies were sent following the infant’s diagnosis and were notable for Babesia microti IgG antibody of 1:2048 (normal <1:64), a negative babesia PCR and a normal peripheral smear. This finding was suggestive of past infection and supported the diagnosis of congenital, vertically transmitted babesiosis. Unlike prior reported cases in which mothers had known tick bites, our patient’s mother had no clinical signs or symptoms of disease either during pregnancy or after delivery.1,2

The patient was admitted to the pediatric hospitalist service for initiation of therapy and monitoring of blood counts. After a review of existing literature on this topic and consultation with Pediatric Infectious Disease, she was started on oral atovaquone and intravenous azithromycin. Her platelet count reached a low of 31,000/mm3 one day after the initiation of therapy, her absolute neutrophil count reached a low of 270/mm3 on day 2 of therapy and her hemoglobin reached a low of 7.3 g/dL on day 4 of therapy. Similar cytopenias are described in all other documented cases of congenital babesiosis.2 Our case differs from some of those previously documented in that no transfusions were given; decisions on transfusion thresholds were complex, involving multiple subspecialists and shared decision making with family coupled with close in-hospital observation.2 On day 4 of therapy, her parasitemia became undetectable by peripheral blood smear. At that time, she was transitioned to oral azithromycin and continued on oral atovaquone. The infant was discharged after 4 days of hospitalization with close primary care and pediatric infectious disease follow-up. She had increasing values in all cell lines by the 7th day of therapy. She completed a total 14-day course of therapy with both antimicrobial agents and has done well with no disease sequelae. Follow-up CBC 2 months after presentation demonstrated complete resolution of the blood count abnormalities.

Babesiosis is a vector-borne disease most commonly caused by the intraerythrocytic protozoa B. microti belonging to the phylum Apicomplexa. It is typically transmitted by the Ixodes scapularis tick.3,4 The majority of babesiosis cases in the United States occur in the Northeast and Northern Midwest regions where the disease is endemic and increasing in incidence.3,4 Since the initiation of annual case tracking in 2011, there has been a reported doubling of cases; however, there are suspected to be high numbers of asymptomatic cases, thus, this may be an underestimate of true disease burden.3,4 Most cases of babesiosis occur in late spring to early autumn when the vector tick and its food sources (primarily mice and deer) are more abundant due to warmer temperatures.4

In addition to B. microti, other species known to cause disease in humans include Babesia ducani, Babesia divergens, and Babesia venatorum.5B. ducani is found in the West and Northwest of the United States and is transmitted via the winter tick (Dermacentor albipictus).6 The winter tick is predominantly a single-host tick and this may explain in part why B. ducani causes disease less frequently than B. microti.6 As a proportion of reported cases, B. ducani appears more likely to be transmitted via blood transfusion than B. microti.7B. divergens, transmitted by Ixodes ricinus, is found in Europe, often causing infection in asplenic or otherwise immunocompromised patients, and has been associated with more severe disease than other species. Less is known about B. venatorum.5

The clinical presentation of babesiosis caused by all species can range from asymptomatic or very mild to severe disease. Symptoms can be nonspecific including fever, body aches, decreased appetite, nausea and vomiting. Other associated signs include cell line abnormalities such as hemolytic anemia, thrombocytopenia and neutropenia. Rarely, severe complications including acute respiratory failure, disseminated intravascular coagulation, congestive heart failure and death may occur, particularly in elderly or immunocompromised patients.3

Neonatal babesiosis remains rare but is also increasing in prevalence. Some regions of the United States have reported a number of cases presumed to have been transmitted transplacentally based on maternal history and serology results.9 An animal study performed in mice and mice embryos demonstrated that transplacental transmission of babesiosis occurs in the wild, further supporting the biologic plausibility of vertical transmission.2 The majority of cases of congenital babesiosis in the literature presented around 4–6 weeks of life with fever and cell line abnormalities, though many also had hepatomegaly and jaundice.8 The rash and petechiae noted in the current case have not been described in previous reports.

Blood transfusions have been identified as another source of neonatal disease. Several cases have been reported, particularly in neonatal intensive care units in endemic areas that describe identification of B. microti on peripheral smear following red blood cell transfusion.9,10 This population notably experiences a broad range of symptomatology, from no associated symptoms despite high parasite loads (up to >9%) to severe illness with respiratory distress, hypotension and splenomegaly.9 Some infants with severe transfusion-related disease have received exchange transfusion to decrease parasite load, and 1 infant, who remained asymptomatic, required retreatment after recurrence of detectable parasitemia following an initial course of therapy.9,10 Finally, some have postulated that tick-borne illnesses such as babesiosis may be transmitted via breast milk; however to our knowledge, there is no specific published literature to support this mechanism of transmission at this time.11

Given the limited literature available on congenital babesiosis, creating a treatment plan for the infant was challenging. Previous case reports describe the use clindamycin and quinine for 7–10 days of treatment; however, a shift in adult therapy toward azithromycin and atovaquone has led to the use of this regimen in infants and children despite limited data.2,12 Typical dosages include 12 mg/kg/day of azithromycin and 40 mg/kg/day divided BID for atovaquone.2,13,14 Optimal treatment duration is also not well understood, with suggested courses ranging from 7 to 10 days for a mild infection to 6 weeks for severe disease.2,15 Our choice of a 14-day course of therapy with azithromycin and atovaquone, transitioning the former to oral once parasitemia had cleared, led to apparently adequate treatment with no sequelae.

Although rare, babesiosis is a potential cause of neonatal fever in endemic geographic regions. While not all infants presenting with a fever, even in endemic areas, should undergo evaluation for babesiosis, a peripheral smear evaluation may be reasonable for those presenting with cell line abnormalities and a clinical history potentially consistent with babesiosis. Furthermore, additional data on the natural history and treatment of babesiosis in infants is needed to aid in the effective management of this patient population.

Please note permission was obtained from family before proceeding with the case report.

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