title: Probable intrafamilial transmission of coxsackievirus b3 with vertical transmission, severe early-onset neonatal hepatitis, and prolonged viral RNA shedding.
abstract: Here we report a familial cluster of 3 cases of coxsackievirus B3 infection: a recent history of illness in a woman's 3-year-old son with a coxsackievirus B3-positive stool culture indicated that he probably infected his mother at home during her last week of pregnancy. Consequently, she delivered an infected neonate who developed severe hepatitis, disseminated intravascular coagulation, and bilateral intracranial hemorrhage. The neonate remained well for the first 2 days of life. On the third day, he developed fever (39 degrees C) and poor peripheral circulation. On the fourth day, he developed petechiae and bruises over his chest wall and extremities, and prolonged bleeding was observed over venipuncture sites. Investigations revealed severe thrombocytopenia (platelets: 41 x 10(9)/L) and a markedly deranged coagulation profile (prothrombin time: 19 seconds [reference: < 10 seconds]; activated partial thromboplastin time: > 120 seconds [reference: 24.2-37.0 seconds], serum D-dimers: 6722 ng/mL [reference: < 500 ng/mL]), suggestive of disseminated intravascular coagulopathy. Clinical examination revealed yellow sclera, hepatomegaly (5 cm), and splenomegaly (2 cm), consistent with hepatitis. Serial chest radiographs showed bilateral pleural effusions, and an ultrasound of the abdomen demonstrated ascites. An echocardiogram showed normal cardiac structure and good contractility of both ventricles. However, a cranial ultrasound revealed bilateral grade 2 intraventricular hemorrhages. Serum C-reactive protein increased to 33.9 mg/L. Liver-function tests were also markedly deranged at this time, with maximum values for serum alanine transferase, bilirubin, alkaline phosphatase, and ammonia concentration of 1354 IU/L, 258 micromol/L, 189 IU/L, and 147 micromol/L, respectively. Serum glucose levels were normal. Over the next 3 days, his fever subsided, and his liver function and clotting profile normalized by day 13 after onset of illness. A stool sample from the older brother, collected 14 days after his onset of illness at home, was positive for coxsackievirus B3 by both virus culture and enterovirus reverse-transcription polymerase chain reaction. He had neutralizing coxsackievirus B3 antibody titers of 1:2560 and 1:1280 on days 14 and 28 after his onset of illness, respectively. No virus was cultured from the mother's stool sample, collected 5 days after her onset of illness, but the enterovirus polymerase chain reaction was positive and maternal sera neutralized the coxsackievirus B3 isolated from the neonate. The maternal sera also showed a more than fourfold rise in antibody titer from 1:80 to 1:640 on days 5 and 16 after her onset of illness, respectively. Neonatal antibody titers also showed a more than fourfold rise from < 1:80 to 1:2560 on days 1 and 21 after his onset of illness, respectively. This demonstrates that both the mother and the neonate had had recent coxsackievirus B3 infections. Serially collected neonatal throat swab and stool samples were culture negative for enterovirus by 4 and 8 days after his onset of illness, respectively. However, enterovirus RNA remained detectable by reverse-transcription polymerase chain reaction in these samples for considerably longer, only becoming undetectable by 16, 23, and 41 days after his onset of illness. We show that even mild household infections may have potentially serious consequences for pregnant women and their infants.
authors.affiliation: Department of Pediatrics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region, China.
authors.forename: Ling Ling
authors.initials: LL
authors.lastname: Cheng
authors.forename: Pak Cheung
authors.initials: PC
authors.lastname: Ng
authors.forename: Paul Kay-Sheung
authors.initials: PK
authors.lastname: Chan
authors.forename: Hiu Lei
authors.initials: HL
authors.lastname: Wong
authors.forename: Frankie Wai Tsoi
authors.initials: FW
authors.lastname: Cheng
authors.forename: Julian Wei-Tze
authors.initials: JW
authors.lastname: Tang
mesh_terms: D000328:Adult; D017668:Age of Onset; D002543:Cerebral Hemorrhage / Q000209:etiology; D002675:Child, Preschool; D004211:Disseminated Intravascular Coagulation / Q000209:etiology; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000150:complications* / Q000635:transmission* / Q000821:virology; D005260:Female; D006505:Hepatitis / Q000209:etiology*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D017201:Virus Shedding