Neonatal tick bites place infants at risk for acquiring infections that have rarely or never been documented in this age group. We describe 2 rare cases of tickborne infection in neonates. The first patient presented with multiple erythema migrans and fever, leading to a diagnosis of early disseminated Lyme disease. The second patient presented with irritability, fever, and worsening anemia due to babesiosis. Both infants had been bitten by arthropods fitting the description of ticks before the onset of symptoms. Our cases demonstrate the clinical course of 2 common tickborne infections occurring at an atypical age, opening the door to new, complex questions for which little guiding data exists. As tickborne infections become more prevalent, we expect other clinicians will be faced with similarly challenging neonatal cases. Providers must use past experience and a keen eye to identify neonates with tickborne infections and sort through their optimal diagnosis and management. In this article, we raise some of the questions we faced and discuss our conclusions.
The incidence of tickborne illnesses has increased dramatically over the last decade,1 with most infections occurring in the Northeast, Mid-Atlantic, and Upper Midwest from spring through late summer.1–3 Despite children being among those most frequently2 and severely3 affected, neonatal infections remain rare because of limited tick exposure. Most published cases of neonatal tickborne infections describe vertically or blood product–transmitted babesiosis.4 Reports of other tickborne infections are sparse, including 1 neonate with babesiosis after a tick bite,5 1 with erythema migrans,6 and 1 with anaplasmosis presumed to be vertically transmitted.7 With little data to guide management, caring for these patients presents many challenges.
In this article, we describe 2 neonates with tickborne infections after witnessed arthropod bites. The unusual circumstance of a neonate being directly infected via tick bite introduces myriad complex clinical questions, which we address by drawing conclusions from these cases.
Scenario 1
A 5-week-old, previously healthy, term infant girl presented to the emergency department in August on Long Island, New York, because of fever and an unusual rash. The fever started 2 days earlier (maximum of 38.4°C), followed by a rash on the face and torso the next day. Her parents reported removing an engorged, black “bug” from behind her left ear 6 days before symptoms started. The infant is rarely outdoors, although the family’s dogs walk outside.
In the emergency department, the infant was febrile and irritable but consolable. Examination was notable for multiple flat rings with peripheral blanching erythema, a central clearing, and outward expansion without tenderness or peripheral scaling (Fig 1), including 1 lesion near the arthropod bite. Remainder of the examination had normal results.
Erythema migrans rash anterior to the left ear and left chest. Note that the rashes are circular, pink with a central clearing, and flat, with outward expansion noted by the family.
Erythema migrans rash anterior to the left ear and left chest. Note that the rashes are circular, pink with a central clearing, and flat, with outward expansion noted by the family.
Pediatric infectious disease providers were consulted and agreed with the pediatrician’s diagnosis of early disseminated Lyme disease. Laboratory results were notable for slight leukocytosis (16 × 103/μL), anemia (hemoglobin 10.1 g/dL), thrombocytosis (523 × 103/μL), and hyponatremia (132 mEq/L) without transaminitis. Lumbar puncture was unsuccessful. Electrocardiogram showed sinus tachycardia. Lyme disease enzyme-linked immunosorbent assay had negative results (Western blot was therefore not performed), and Borrelia burgdorferi blood polymerase chain reaction (PCR) also had negative results. Anaplasma phagocytophilum PCR, Babesia blood smears, and blood and urine cultures all had negative results.
The infant received 14 days of intravenous (IV) ceftriaxone for treatment of early disseminated Lyme disease on the basis of the presence of multiple erythema migrans8 along with an inability to rule out Lyme meningitis. She defervesced, and the rash resolved on hospital day 2; she remained well throughout the admission and was discharged after completing 14 days of IV antibiotics. There were no complications at follow-up.
Scenario 2
A 6-week-old, previously healthy, term infant boy presented to a Long Island hospital in June with 1 day of irritability, poor feeding, emesis, and fever (38.4°C). Laboratory results showed anemia (hemoglobin 8.4 g/dL), a normal white blood cell count (8.4 × 103/μL), and thrombocytopenia (50 × 103/μL). Electrolytes and transaminases had normal results. A blood culture was obtained, and ampicillin, ceftriaxone, and vancomycin were started. He was then transferred to our institution.
On arrival, he had normal vital signs and appeared tired. Examination was notable for a grade II of VI flow murmur, no palpable liver, and a spleen palpated to 2 cm below the costal margin. The remainder of the examination was unremarkable. Repeat testing showed worsening anemia (hemoglobin 7.4 g/dL) and thrombocytopenia (39 × 103/μL) with elevated alanine aminotransferase (84 U/L; normal for age <45) and aspartate aminotransferase (109 U/L; normal <80). The pediatric team was then notified of intraerythrocytic parasites on manual differential, likely Babesia, with 3.6% parasitemia.
Pediatric infectious disease providers were consulted, and on further questioning, his mother reported a bloody “flea” on his arm 20 days before presentation. The family lives in a tick-endemic area with tall grasses outside their home. They have no pets, and the infant spends minimal time outside, although his father paints home exteriors. The infant had never received blood products. His mother denied ever having babesiosis, was not anemic, and had no febrile illnesses during or after the pregnancy. Maternal blood smear and placenta evaluation had negative results for Babesia. Requested maternal Babesia antibody testing was not completed.
On the basis of the relatively low parasitemia and reassuring hemodynamics, oral atovaquone and IV azithromycin were started. His hemoglobin reached a nadir of 6.9 g/dL, requiring 1 packed red blood cell transfusion. Confirmatory whole blood Babesia microti PCR returned with positive results. Parasitemia resolved on hospital day 4, and he was discharged to complete 10 days of atovaquone and azithromycin. Although Lyme disease coinfection was unlikely, an empirical 14-day course of amoxicillin was also administered.8 Lyme serology was not obtained because of the expected limitations of interpreting results in a neonate. The infant’s repeat Babesia blood smear had negative results 1 week after discharge, and he remained well at follow-up.
Discussion
We present 2 unique cases of neonates with tickborne infections, likely acquired postnatally through tick bites. Similar published cases are rare, leaving little data to guide clinicians. We aim to address those issues and raise lingering questions.
Neonates with tickborne infections can present with symptoms typical of other neonatal infections, including fever, hypothermia, irritability, and poor feeding. Tickborne infections should therefore be considered when an infant in an endemic region has clinical findings that stray from the expected course of more common neonatal infections. Asking about witnessed tick bites (or other “bugs”), recent family or pet exposures to ticks (which may be carried into the home), maternal infections during pregnancy, and transfusion history may provide helpful information.
Examination findings may reveal diagnostic clues. A single erythema migrans rash or multiple erythema migrans rashes is typically adequate to diagnose Lyme disease in an endemic area, although a similar rash may occur after a lone star tick bite due to southern tick-associated rash illness. The presence of systemic symptoms and multiple lesions made Southern tick-associated rash illness unlikely in our patient.9 We hypothesize that infants, like older children, may develop arthritis, facial nerve palsy, bulging fontanelle suggestive of meningitis, or hemodynamic instability due to carditis. Immature neonatal immune defenses may increase disease severity, as demonstrated by our patient’s rapid progression to early disseminated Lyme disease. Infants with babesiosis may present with splenomegaly or signs of acute anemia. A maculopapular, petechial, or purpuric rash should raise consideration of ehrlichiosis or Rocky Mountain spotted fever (RMSF) if present in the appropriate geographic region.
Lyme disease generally presents without laboratory abnormalities, although pathogen-specific testing may assist diagnosis. Our patient had transaminitis, leukocytosis, and thrombocytosis, likely representing nonspecific inflammation. Neonatal serology interpretation is limited by poor antibody production and the presence of maternal antibodies. An elevated convalescent immunoglobulin M provides evidence of acute Lyme disease, although many initially seronegative patients will remain so after treatment.10 Our evaluation included B burgdorferi serum PCR, but the test is limited by poor sensitivity.11 Skin biopsy PCR and culture of an erythema migrans has high sensitivity12 but was considered excessively invasive in our case. We suggest an electrocardiogram and lumbar puncture with paired serum and/or cerebrospinal fluid Lyme antibody testing to diagnose carditis and meningitis, respectively. In our case, no laboratory test definitively diagnosed Lyme disease.
Blood smears are often sufficient for diagnosing babesiosis in neonates, who often have high parasitemia levels.4 If smear results are negative, Babesia blood PCR may aid diagnosis. Vertical Babesia transmission may be assessed with maternal serology. In our case, the negative maternal Babesia blood smear result and placenta examination, the infant’s relatively old age for congenital babesiosis,4 and the witnessed arthropod bite all made vertical transmission unlikely.
Given the scarcity of published neonatal ehrlichiosis, anaplasmosis, and RMSF cases, it is unknown if neonates present with “classic” laboratory abnormalities. If a febrile infant presents with hyponatremia, leukopenia, and transaminitis in an endemic region, one could test for and empirically treat these infections to minimize potentially devastating outcomes. Acute and convalescent serology may assist diagnosis. Blood PCR results may be positive during the acute illness,11 although low sensitivity and false-positive results due to contamination limit clinical utility.
One unique challenge of infection after a tick bite is the risk of coinfection, particularly with Lyme disease and babesiosis.13 Although uncommon, coinfection risk increases with greater local pathogen prevalence and longer duration of tick attachment.14 Ixodes scapularis ticks may transmit Babesia, B burgdorferi, or Anaplasma along with emerging pathogens, including Powassan virus, Ehrlichia muris euclariensis, and Borrelia mayonii. Given the diagnostic challenges, empirical treatment could be considered if ancillary laboratory testing or clinical features suggest a coinfection.
Antibiotic management varies by tick infection. No data exist to specifically guide Lyme disease management in neonates, so we referred to American Academy of Pediatrics Red Book8 recommendations. We treated the patient with IV ceftriaxone, rather than amoxicillin, because our patient had evidence of early disseminated Lyme disease, and Lyme meningitis could not be ruled out.
Relevant to the treatment of Lyme disease, ehrlichiosis, anaplasmosis, and RMSF, recent changes in the Red Book8 allow up to 21 days of doxycycline in children of any age. Nevertheless, the risk of dental staining is likely greatest in neonates, so we would use alternative antibiotics when possible. As a life-saving measure in critical illnesses such as RMSF, the updated Red Book does provide reassurance against long-term adverse effects.
Babesiosis is preferentially treated with atovaquone plus azithromycin, rather than clindamycin plus quinine, because of better tolerance.8,15 Exchange transfusion is sometimes necessary, particularly with high parasitemia or hemodynamic instability.
Much remains unknown about neonatal tickborne infections. The signs and symptoms of infection in our patients paralleled those of older patients, although additional data are needed to better understand the clinical course of tickborne diseases in neonates and how this compares to manifestations in adults. Additionally, there are no clinically validated or US Food and Drug Administration–approved tests for tickborne infection in this age group. In presenting these cases, we aim to provide guidance to other clinicians, although many questions remain unanswered.
Dr Handel drafted the initial manuscript, conceptualized and designed the study, and reviewed and revised the manuscript; Drs Hellman and Hymes conceptualized and designed the study and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted.
FUNDING: No external funding.
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