Age: 0.1
Sex: M
Vaccine: HEP
Symptoms: Fibrin D dimer increased, Grunting, Haemangioma, Haematocrit decreased, Haemoglobin decreased
Clinical narrative: This case was reported in a literature article and described the occurrence of babesiosis in a 35-day-old male subject who was vaccinated with Hepatitis B vaccine (manufacturer unspecified). The subject lived with his parents, his twin and an older sibling in a suburban, forested neighbourhood where the mother frequently walked. The parents had gone on holidays to an island approximately 2.5 months before the event. They had been out of the country years earlier too, which had been their only international travel. The parents reported that they had had upper respiratory tract symptoms recently. The family had a pet dog. The subject had been born by caesarean section due to fraternal twin pregnancy and breech presentation at 37.5 weeks of gestation. The pregnancy had been uncomplicated and his mother had received prenatal care that included prenatal screening tests for gonorrhoea, chlamydia, syphilis, group B streptococcus, human immunodeficiency virus and hepatitis B virus. The results for all of them had been negative. Her rubella immunity screening test had been positive. Prior to the delivery there had been no prolonged rupture of membranes (ruptured less than 24 hours before delivery) and antibiotic drugs had been administered. Apgars results were 9 at 1 minute and 9 at 5 minutes. He had received an unspecified hepatitis B vaccine before been discharged from hospital. He was mixed fed (breast milk and formula). On an unspecified date, during the routine 1-month examination at the pediatrician which was done 2 days before admission, the subject received 2nd dose of Hepatitis B vaccine (unknown route of administration and batch number). One day after vaccination with Hepatitis B vaccine, the subject's mother noticed an increased fussiness, pale and warm skin and one episode of vomiting. On the next day, the subject was taken to his pediatrician with a complaint of fever, vomiting, mottled skin and severe anaemia. Tachycardia was noted and the vomiting had increased. On examination at the paediatrician's office, the subject was pale with mottled skin and his temperature was 38.6?C. He was referred immediately to the emergency department of an hospital. On clinical examination at the emergency department, his weight was 3.61 kg, rectal temperature 38.0?C, blood pressure 113-63 mm Hg, pulse 172 beats per minute, respiratory rate 64 breaths per minute and his oxygen saturation 97% on air. The subject was pale, listless and fussy, with mild suprasternal and intercostal retractions but without grunting, nasal flaring, apnoeic episodes or desaturation events. He had a brisk capillary refill. He responded vigorously during the evaluation for sepsis, although he quickly feel asleep when not bothered. The rest of the examination was normal. Samples of the blood, urine and cerebrospinal fluid were obtained for different tests and culture. His ABO type was O, Rh positive and the antibody screening was negative. Serum renal function test, electrolytes levels, glucose, calcium, magnesium, alkaline phosphatase, and alanine aminotransferase were normal. Haematocrit level was 16.9%, haemoglobin was 6.1 g/dl, platelet count was 23,000 per mm3 and neutrophil level was 6%. The rest of the full blood count results were within normal range. The urine sample was dark red and cloudy. On dipstick urine analysis the pH was 7.0, the specific gravity 1.015, there was a large amount of blood, 100 mg/dl of protein and traces of leukocyte esterase. Urine analysis also revealed 0 to 5 red cells and white cells per high-power field and a small amount of bacteria, a moderate number of epithelial cells and 15 to 20 granular casts per low-power field. Examination of a peripheral-blood smear revealed that 35 to 40% of the erythrocytes contained multiple ring forms. Treatment was started with IV ceftriaxone, ampicillin and a bolus of normal saline, as well as a transfusion of leukocyte-depleted, packed red cells (type O, Rh-negative). The subject was severely anaemic with signs of respiratory distress and tachycardia, so a transfer to a Paediatric ICU in another hospital was arranged within 4 hours of the admission. On route, the subject received IV clindamycin, crystalloid solution and the remainder of the red-cell transfusion as well as oxygen through a nasal cannula. On arrival to the second hospital, the subject was crying vigorously and had pale and mottled skin. His temperature was 39.1?C, blood pressure 101/69 mm Hg, pulse 176 beats per minute, respiratory rate was 68 breaths per minute with supraclavicular, intercostal, and subcostal retractions and the oxygen saturation was 97% on 1 L of oxygen via nasal cannula. The anterior fontanelle was soft and flat, and there was no scleral icterus. A holosystolic-flow murmur, grade 2/6, was heard. The abdomen was soft, without tenderness or distension and the spleen was palpated 2 to 3 cm below the costal margin. The arms and legs were mottled and slightly cool. The remainder of the examination was normal. The working diagnosis at that point was infection with Babesia microti with/without a coinfection with other tick-borne pathogens; so antimicrobial treatment was broadened by adding quinine to augment therapy for babesiosis and doxycycline to target other tick-borne pathogens. Post-transfusion full blood count revealed findings consistent with haemolytic anaemia, thrombocytopenia and elevated level of aspartate aminotransferase. Haematocrit level was 20.9%, haemoglobin was 7.6 g/dl, platelet count was 36,000 per mm3, erythrocyte count was 2,390,000 per mm3, neutrophils level was 9% and aspartate aminotransferase was 134 U/liter. The prothrombin time and international normalized ratio were normal, although the elevated D-dimer level, borderline fibrinogen level and thrombocytopenia suggested the presence of at least some component of compensated disseminated intravascular coagulation. The subject showed evidence of ongoing haemolysis, including an elevated level of lactate dehydrogenase, haemoglobinuria and splenomegaly. He had mildly elevated aminotransferase levels but no evidence of acidosis, renal dysfunction, or other metabolic derangements. Thick and thin peripheral-blood smears were examined for parasites. Numerous intraerythrocytic and occasional extraerythrocytic structures of different sizes and with different morphologic features were present. Many erythrocytes contained one or two large ring forms, features that in conjunction with the epidemiologic history were consistent with B. microti. A number of erythrocytes contained four ring forms, which was likely to represent the stages that occur after the breakdown of the tetrad configuration ('Maltese cross'). In addition, further blood testing was performed to rule out infection with other tick-borne pathogens. Blood culture, polymerase-chain-reaction (PCR) -based tests for anaplasma and Ehrlichia species and serologic tests for IgM and IgG antibodies against Borrelia were negative. Diagnosis at this point was either congenital or acquired Babesia microti infection. Management included the placement of an arterial catheter for haemodynamic monitoring and an exchange transfusion. During the transfusion the subject required calcium repletion once for hypocalcaemia but his general condition seemed to improve and became stable; so when the infusion catheter stopped functioning midway through the planned double-volume exchange transfusion it was decided to wait for the results of a thin peripheral-blood smear to assess the parasitemia level and to proceed with the procedure only if the parasitemia level exceeded 10%. The parasitemia level was 5.2% so the procedure was discontinued. On day 2 the parasitemia level returned to 10% but it was decided not to continue the exchange transfusion because of his continuous clinical improvement. The subject received a second platelet transfusion due to a low platelet count (24,000 per mm3). The administration of ampicillin and ceftriaxone was discontinued as the urine, blood and cerebrospinal fluid cultures that had been performed at the first hospital reportedly showed no growth. However, due to recurrent fevers that occurred later that evening and persistent neutropenia, a repeat blood culture was performed, and an empirical, short course of cefepime was initiated while awaiting the results. By day 6, it was reported that the subject had been afebrile for 72 hours so he was no longer requiring intensive monitoring and he was transferred to the general paediatric service. He was still anaemic and neutropenic but had signs of adequate end-organ perfusion and resolution of his respiratory distress. His skin was no longer mottled and the murmur was no longer detected. He was feeding well by mouth and was more alert and no longer fussy. His medications at the time of transfer were quinine, clindamycin, and iron supplements. Doxycycline had been discontinued when test results for anaplasma came back normal. Daily peripheral-blood smears continued to show a drop in parasitemia levels and by day 8, only a single ring form was seen on the thin smear. Twenty-one days after the initiation of treatment, thick and thin peripheral blood smears were negative for Babesia. The parasite load at discharge was undetectable. His mediations were switched to azithromycin and atovaquone on discharge. The subject was seen at a follow-up visit 1 week later. He had completed the course of antibiotics and the hematocrit level had improved. At the time of reporting, the outcome was considered as resolved. The twin and mother were tested and examined for Babesia at the time of the subject's diagnosis but no morphologic evidence of it was found. Also, PCR tests of blood samples collected from the twin and mother at the time of diagnosis were negative for Babesia. However, antibodies against B. microti were detected in blood samples from both the twin and the mother at a high titer of 1:4096, and antibodies against B. microti were present at a titer of 1:1024 in a blood sample from the subject that was taken after the exchange transfusion. Furthermore, Babesia could be detected in placental tissue and in dried blood spots collected during neonatal screening at the time of delivery. Formalin-fixed, paraffin-embedded placental tissue was sent to the CDC for immunohistochemical staining and PCR testing but both methods failed to detect Babesia in the placental tissue. PCR testing of the dried blood spots, also performed at the CDC, was negative for Babesia. Although PCR testing did not detect nucleic acids from Babesia, the presence of high-titer antibodies against B. microti in the subject, his twin, and his mother suggests that the mother became infected during pregnancy and the patient acquired the infection in utero. Based on these investigations the final diagnosis was babesiosis, most likely congenitally acquired. Relevant test results included [laboratory results/hospital investigations]. The subject was treated with ceftriaxone, Ampicillin, Normal saline, Packed red blood cell transfusion, clindamycin, crystalloid solution, oxygen, quinine, Doxycycline, Platelet transfusion, cefepime, azithromycin, atovaquone, Calcium and Iron supplement. At the time of reporting the events were resolved. The author considered the events were unlikely to be related to vaccination with Hepatitis B vaccine.