|Year : 2018 | Volume
| Issue : 3 | Page : 127-129
Use of IV immunoglobulin in a case with neonatal enterovirus sepsis
Mahmoud Galal Ahmed, Muzammil Hafeez, Anwar Khan, Mostafa Abdul Rauf El Bolkini, Niyas Parammal Ambadi
Department of Paediatric, Neonatal Intensive Care Unit, Dubai Hospital, Dubai, UAE
|Date of Web Publication||24-Sep-2018|
Department of Paediatric, Neonatal Intensive Care Unit, Dubai Hospital, P. O. Box: 7272, Dubai
Source of Support: None, Conflict of Interest: None
Enterovirus (EV) infection in the newborn period can present with non-specific symptoms or with serious and fatal complications. Mortality is essentially 100% with EV sepsis. Here, we present a case of EV sepsis, diagnosed with a positive polymerase chain reaction for EV, who recovered completely after treatment with intravenous immunoglobulin.
Keywords: Enterovirus sepsis, immunoglobulin, neonatal
|How to cite this article:|
Ahmed MG, Hafeez M, Khan A, El Bolkini MA, Ambadi NP. Use of IV immunoglobulin in a case with neonatal enterovirus sepsis. Hamdan Med J 2018;11:127-9
| Introduction|| |
Enteroviruses (EVs) are among the most common viruses causing disease in humans. It has been estimated that in the USA alone, 10–15 million symptomatic EV infections occur each year. EV infections are not an uncommon cause of sepsis-like illness in the neonatal period. There is an evidence suggesting that EV infections can be acquired antenatally, intrapartum or postnatally. Infection occurs in 20%–50% of infants in whom there is a maternal history of illness in the week preceding delivery. The severity of the neonatal illness is related to the severity of maternal illness at the time of delivery as well as to the age of the infant at onset of infection. Both epidemic outbreaks and sporadic transmission of EVs in neonatal units and hospital nurseries have been described. Notably, nosocomially acquired EV infections are generally associated with less severe disease and lower mortality rates than vertically acquired infections. A wide range of clinical disease has been reported in neonates, including non-specific febrile illnesses, exanthems and aseptic meningitis. Neonates are at high risk of disseminated disease resulting from EV infections acquired during the perinatal period. Severe EV diseases such as meningoencephalitis, severe hepatitis and myocarditis occur mostly in the neonatal period.
Although many EVs cause severe, fulminant disease in neonates, the same viruses produce mostly self-limited or asymptomatic disease in immunocompetent older children and adults. The reasons for the age-related differences in severity of illness are not fully understood. There may be either an increased susceptibility of the newborn host's tissues to virus infection, a diminished immune response by the newborn or both. Infants younger than 10 days of age are at higher risk for severe disease because of their relative inability to mount a significant immune response and their lack of serotype-specific maternal antibody. The immune response of the neonate to enteroviral infection may be impaired relative to the older host. Clinical and laboratory observations suggest that the humoral immune response and macrophage function each play a role in limiting the replication and spread of EVs in vivo, while T-cell lymphocyte function has a lesser role, if any.
Presenting symptoms are non-specific including fever, irritability, lethargy and poor feeding. Half of the patients develop respiratory symptoms, including nasal discharge, cough, apnoea, tachypnoea, recessions, grunting and nasal flaring. The sepsis-like clinical picture often is indistinguishable from bacterial sepsis. Fulminant and, at times, fatal disease manifests as pneumonitis, hepatitis, disseminated intravascular coagulation and meningoencephalitis. Other potential manifestations include pancreatitis, adrenal haemorrhage and necrotising enterocolitis. Substantial mortality rates have been reported, and long-term sequelae may occur among survivors. In a recent study profiling EV infection in the first 2 weeks of life, 17% of infected infants developed severe, multisystem disease. Mortality is lowest (10%) for babies with meningoencephalitis, there is 50% mortality in babies with myocarditis and there is essentially 100% mortality in babies with EV sepsis. Non-polio-EVs are the leading cause of exanthems in children. The rash may be the sole manifestation of infection or may present in association with febrile illness or aseptic meningitis. A non-specific rash, which is frequently macular or maculopapular in nature, is observed in around half of infants during the course of the illness.
The mainstay of diagnosis has traditionally been viral isolation in tissue culture; the polymerase chain reaction (PCR) has been demonstrated to be more sensitive than culture, highly specific and rapid. Reverse transcriptase PCR may increase the detection rate in EV infections and is particularly useful in the analysis of cerebrospinal fluid (CSF) samples in patients with evidence of meningitis.
Serology, which relies on the detection of IgM antibodies or the detection of a significant rise in IgG antibody titre, is generally less useful in the diagnosis of EV infections.
Immunoglobulin (Ig) has been used as a therapeutic agent for neonates with EV disease; however, clinical efficacy has not been proven. Some evidence suggests that administering intravenous IG (IVIG) in neonatal EV infections can result in faster cessation of viraemia. A specific recommended dose is not known, but 400 mg/kg/day for 4 days or 2 g/kg in 1 dose has been used.
| Case Report|| |
A male baby was born by normal vaginal delivery to a 36-year-old mother at 36-week gestation. The mother has type II diabetes mellitus on insulin and Glucophage. She is also diagnosed with hyperlipidaemia and was on medication.
During her pregnancy, she had multiple episodes of upper respiratory tract infection (URTI). At 27-week gestation, she also had pneumonia with severe respiratory distress requiring admission to high dependency area for 14 days and was treated with antibiotics and hydrocortisone. Her H1N1 viral screen and Legionella antibodies were negative and her Legionella antibodies were negative. Her echo was normal. Chest X-ray was suggestive of pneumonia. She had no group B streptococcus growth in high vaginal swab culture, and there was no history of premature rupture of membranes.
The mother developed fever 3 days before delivery and was resolved with paracetamol.
The baby's Apgar score was good and the baby was active. The baby had skin mottling since birth and he was observed in the postnatal ward. He developed hypoglycaemia on day 1, hence admitted to the Neonatal Intensive Care Unit. His initial septic screen was negative. His blood sugars stabilised and he was on full feeds. On day 5 of life, the baby became lethargic and developed respiratory distress requiring ventilator support for 2 days. He was given ceftazidime and ampicillin. His C-reactive protein (CRP) was positive [Table 1], his full blood count (FBC) was normal [Table 2], blood culture was sterile and CSF study was normal. Echo and metabolic screen were normal. Hepatitis was ruled out by a normal liver function test (LFT) [Table 3].
In spite of blood culture and CSF culture being sterile baby continued to have respiratory distress, his skin mottling increased and the baby became more lethargic. The baby was investigated for viral aetiology. His virology studies showed PCR positive for EV in the blood. CSF PCR for EV was negative. IVIG 500 mg/kg was started on the 6th day and was given once daily for 4 days. He became afebrile active and was feeding well. The baby was followed up in the outpatient clinic. He is growing well and active and his repeated PCR for EV is negative.
The investigations undertaken included:
- FBC [Table 1]
- CRP [Table 2]
- Blood culture showed no growth
- Urea – 9 mg/dl and electrolytes: sodium – 136 mmol/L, potassium – 4.9 mmol/L and creatinine – 0.4 mg/dl
- LFT normal [Table 3]
- EV RNA PCR is positive on five occasions
- Repeated EV RNA PCR is negative
- Cholesterol – 96 mg/dl (50–170)
- Triglycerides – 74 mg/dl (40–200)
- High-density lipoprotein – 39 mg/dl >35
- Low-density lipoprotein 42 mg/dl (0–170)
- HSV 1 and 2 PCR negative
- CSF normal study: CSF protein 78 mg/dl. CSF glucose47 mg/dl
- Thyroid function test: Free T4 20.8 pmol/L (13.9–26.1)
- Thyroid-stimulating hormone – 0.4 uIU/ml (1.4–8.8).
| Discussion|| |
The baby was born by normal vaginal delivery to a 36-year-old mother at 36-week gestation with good Apgar score. During the course of the pregnancy, the mother had multiple episodes of URTI and one episode of pneumonia requiring high dependency care and treatment in the hospital. At birth, the baby was active and had skin mottling. He had hypoglycaemia which resolved. His initial septic screen was negative. Later on day 5 of life, the baby developed sepsis-like picture with respiratory distress, lethargy and increasing skin mottling. His CRP was positive. Blood culture was sterile and CSF study was normal. He was treated with antibiotics, but he continued to have sepsis-like picture. Viral studies showed EV RNA PCR positive. EVs are among the most common viruses causing disease in humans. EV infections in the neonate are associated with a wide spectrum of signs and symptoms, which range from a non-specific febrile illness to potentially fatal multisystem disease, frequently referred to as ‘neonatal EV sepsis’ or ‘enteroviral sepsis syndrome’. Despite the protean skin manifestations, the presence of a rash is an important finding when considered together with the other clinical features. The presence of skin mottling in the baby at birth and positive maternal history may indicate the antenatal acquisition of the infection. There is an evidence suggesting that EV infections can be acquired antenatally, intrapartum and postnatally. The onset of clinical signs before 7 days of age indicates a perinatal transmission. Further evidence for antenatal transmission comes from the fact that specific neutralising IgM antibodies have been detected on the 1st day of life in a number of neonates. Other modes of transmission include intrapartum exposure to maternal blood, genital secretions and stool as well as postnatal exposure to oropharyngeal secretions from the mother and other individuals who have close contact with the baby. Clinically, there were no signs of myocarditis in the baby and also myocarditis was ruled out by echocardiography. Some neonatal cases develop signs of myocarditis, such as cardiac arrhythmias, cardiomegaly, poor ventricular function, systemic hypotension, congestive heart failure, pulmonary oedema and myocardial ischaemia., The baby did not have signs of hepatitis and his LFTs were normal. Approximately half of the infants with neonatal EV infection have evidence of hepatitis or jaundice during the course of the illness, while hepatomegaly is detected in around 20%., Furthermore, meningitis was ruled out. Infants younger than 10 days of age are at higher risk for severe disease because of their relative inability to mount a significant immune response and their lack of serotype-specific maternal antibody. Clearance of EV infections depends on humoral immune factors and IVIG has been used in neonates and immunodeficient children. EV sepsis carries a mortality of essentially 100%.
Because of the severity of the symptoms and rapid deterioration of the baby's clinical condition, he was treated with IVIG for 4 days. He improved gradually with complete recovery and was discharged. His repeat PCR for EV has become negative. On follow-up in the neonatal outpatient clinic, he is thriving well and is developmentally normal.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflflicts of interest.
| References|| |
Tebruegge M, Curtis N. Enterovirus infections in neonates. Semin Fetal Neonatal Med 2009;14:222-7.
Zaoutis T, Klein JD. Enterovirus infections. Pediatr Rev 1998;19:183-91.
Noor A, Krilov LR. Enterovirus infections. Pediatr Rev 2016;37:505-15.
Freund MW, Kleinveld G, Krediet TG, van Loon AM, Verboon-Maciolek MA. Prognosis for neonates with enterovirus myocarditis. Arch Dis Child Fetal Neonatal Ed 2010;95:F206-12.
Modlin JF. Fatal echovirus 11 disease in premature neonates. Pediatrics 1980;66:775-80.
Abzug MJ. Presentation, diagnosis, and management of enterovirus infections in neonates. Paediatr Drugs 2004;6:1-10.
John Cloherty P, Eric Eichenwald C, Anne Hannsen R, Ann Stark R. Viral infections/enteroviruses. Manual of Neonatal Care. 17th
ed. India, New Delhi: Wolters Kluwer, Lippincott Williams & Wilkins; 2012. p. 618-9.
Khetsuriani N, Lamonte A, Oberste MS, Pallansch M. Neonatal enterovirus infections reported to the national enterovirus surveillance system in the United States, 1983-2003. Pediatr Infect Dis J 2006;25:889-93.
Modlin JF. Perinatal echovirus and group B coxsackievirus infections. Clin Perinatol 1988;15:233-46.
Verma NA, Zheng XT, Harris MU, Cadichon SB, Melin-Aldana H, Khetsuriani N, et al.
Outbreak of life-threatening coxsackievirus B1 myocarditis in neonates. Clin Infect Dis 2009;49:759-63.
Clavell M, Barkemeyer B, Martinez B, Craver R, Correa H, Gohd R, et al.
Severe hepatitis in a newborn with coxsackievirus B5 infection. Clin Pediatr (Phila) 1999;38:739-41.
[Table 1], [Table 2], [Table 3]