SEVERE NEONATAL ECHOVIRUS 17 INFECTION DURING A NURSERY OUTBREAK

Abstract

The manifestations of neonatal enterovirus disease range from inapparent infection to overwhelming severe disease.1 Prematures and infants lacking transplacentally acquired virus-neutralizing antibodies (VNA) are at increased risk for severe enterovirus disease.2 Echoviruses 6 and 11 are the most frequently reported causes of severe enterovirus disease.1 Echovirus 17 is a less prevalent enteroviral strain and a rare cause of mild neonatal illness.3-5 A single nursery outbreak of echovirus 17 infection,5 as well as sporadic cases of fatal echovirus 17 pneumonitis beyond the neonatal period, have thus far been reported.5, 6 We report a nursery outbreak of echovirus type 17 with two lethal outcomes caused by sepsis-like disease. Methods.Outbreak description. The outbreak occurred in the nursery unit, General City Hospital, Belgrade, in September, 1994. The total number of deliveries in 1994 was 2102 with 6% premature births and perinatal mortality rate of 12 per 1000 births. The nursery had two wards on two separate floors. The average length of stay in the nursery was 5 days. Breast-feeding was routinely introduced 24 h after birth. All premature babies with birth weights of <1500 g were routinely referred to a tertiary care hospital. The mother of the index patient was admitted on September 3, 1994. Five days later she gave birth to a full-term baby. She did not report that she was ill before the admission. Her baby developed fever and rash on September 13. Over the next 48 h another 2 infants developed febrile illness on the same ward (Table 1). We suspected that enterovirus could be the cause of this outbreak, and the nursery was closed on September 15, 1994. Twenty-three asymptomatic infants were discharged home from the nursery. Another 3 babies developed an echovirus 17 disease at the other nursery ward between September 19 and September 21. A total of 87 babies were born between September 5 and September 19, 1994. Two infants who were discharged from the nursery and developed severe echovirus 17 disease at home were admitted to our neonatal intensive care unit on September 16 and September 19, 1994, respectively.TABLE 1: Patient characteristics, clinical features, viral investigations and outcome of echovirus 17 infection during an nursery outbreak Virologic investigations. Virologic diagnostics at the national WHO laboratory for enteroviruses during this outbreak included: (1) stool, cerebrospinal fluid (CSF) and throat swab specimens for viral cultures obtained from all symptomatic infants; (2) stool and throat swab specimens obtained from 23 symptomatic infants on discharge, mothers of symptomatic infants, medical staff and personnel; (3) paired sera taken from all symptomatic infants and their mothers for VNA titer determination. Conventional virus isolation techniques based on primary monkey kidney tissue culture were used. Enteroviruses were identified by a neutralization test with serotype-specific antisera (Statens Seruminstitut, Copenhagen, Denmark). Infection was confirmed by positive viral culture and/or a 4-fold VNA titer rise in convalescent sera. Severe enterovirus disease was defined as serious liver, heart or brain involvement with or without disseminated intravascular coagulation (DIC).1 Results.History of Patient 2. On September 8, a 2700-g birth weight, 36-week gestation male infant was born to a healthy multigravida. Apgar scores were 8 and 9 at 1 and 5 min. He was discharged from the nursery on September 13. On the ninth day of life the infant developed fever, apneic crisis and generalized seizures. He was admitted to our neonatal intensive care unit. Brain ultrasound was normal. Blood analysis showed a white blood cell count of 26.0 × 109/l with 18% neutrophils and 80% lymphocytes; the platelet count was 40 × 109/l; C-reactive protein was normal. The liver function tests showed elevated aspartate aminotransferase at 282 units/l (normal, 10 to 25 units/l) and lactate dehydrogenase at 1986 units/1 (normal <299 units/l). On the third day of hospitalization the infant developed extensive spontaneous bleeding and ventricular tachycardia. Despite all therapeutic measures infant died on the fourth day after onset of the first symptoms. The parents refused an autopsy. All bacterial cultures remained negative but viral cultures of CSF, pharynx and stool were positive for echovirus 17. Viral cultures taken from the mother were negative. History of Patient 7. On September 12, a 2250-g birth weight, 32-week gestation male infant was born to a healthy multigravida. The Apgar scores were 9 and 9 at 1 and 5 min. On the seventh day of life the infant developed fever (39°C), lethargy and poor feeding. On admission his abdomen was distended with a firm, enlarged liver. Blood analysis showed a white blood cell count of 16.6 × 109/l with 4% band forms, 36% neutrophils and 56% lymphocytes; the platelet count was 60 × 109/l; C-reactive protein was normal. There was laboratory evidence of liver dysfunction (aspartate aminotransferease 217 units/l, lactate dehydrogenase 1739 units/l) and DIC. Twenty-four hours later the infant died because of severe DIC. The viral cultures of CSF, throat and stool obtained on day 8 of life yielded echovirus 17. The relevant findings of the postmortem examinations were those of hemorrhagic necrosis of the liver and adrenals and disseminated organ thrombosis. Postmortem cultures of blood, brain, meninges, intestines and liver yielded echovirus 17. Virologic investigations. Investigations included 28 infants and 4 mothers. Echovirus 17 infection was confirmed in 8 infants and in the mother of the index patient. Their characteristics, clinical features and laboratory data are shown in Table 1. Echovirus 17 infection was also confirmed in 1 doctor, 2 nurses and 1 maid. The risk for symptomatic echovirus 17 infection was 8% during this outbreak. The overall attack rates for echovirus 17 infection were not calculated because we could not perform viral isolation studies in all asymptomatic infants. Discussion. Echovirus type 17 is one of the less frequently isolated types during the enterovirus season in temperate climates.1, 2 In this outbreak seven of our patients developed symptomatic echovirus 17 infection and two of them had severe clinical manifestations. The most common organ affected in neonatal echovirus infection is the central nervous system. Echoviral meningoencephalitis is rarely fatal in the absence of associated myocarditis or pneumonitis.2 In our first patient we strongly suspected myocarditis but we could not confirm it because an autopsy was not performed. A second, more severe syndrome results from systemic echovirus infection with hepatic necrosis.1, 2 The main clinical syndromes of severe echovirus disease may overlap because both our patients had central nervous system symptoms, hepatic involvement and DIC. Severe neonatal echovirus 17 disease has been rarely reported in the past. In 1973 Faulkner and van Rooyen5 first reported an echovirus 17 nursery outbreak. Seven premature infants developed mild illness whereas one infant had meningoencephalitis. The same authors described an unrelated case of disseminated echovirus 17 disease in a 5-week-old infant who died of echovirus 17 pneumonitis.5 Another case of fatal echovirus 17 pneumonitis was reported in a 6-month-old infant with cerebral palsy.6 Echoviruses 5, 6, 11 and 16 have been most frequently reported as the cause of severe neonatal disease1, 2 and other serotypes sporadically cause fatal disease.7-9 To our knowledge our two patients represent the first reported cases of sepsis-like neonatal echovirus 17 disease during a nursery outbreak. Borisav Jankovic, M.D., Ph.D. Srdjan Pasic, M.D., M.Sc. Borisava Kanjuh, M.D., Ph.D. Katarina Bukumirovic, M.D., Ph.D. Gordana Cvetanovic, M.D., M.Sc. Nada Todorovic, M.D. Slavisa Djuricic, M.D.