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Cytomegalovirus: A cause of colonic stricture in a premature infant
Journal of Infection (2007) 54, e37ee39
www.elsevierhealth.com/journals/jinf
CASE REPORT
Cytomegalovirus: A cause of colonic stricture in a premature infant Anjali Shetty a,*, Rosemary Barnes a, Ed Lazda b, Cora Doherty c, Nicola Maxwell c a
University Hospital of Wales, Microbiology, Heath Park, Cardiff, United Kingdom University Hospital of Wales, Histopathology, Heath Park, Cardiff, United Kingdom c University Hospital of Wales, Neonatology, Heath Park, Cardiff, United Kingdom b
Accepted 21 March 2006 Available online 9 May 2006
KEYWORDS Cytomegalovirus; Neonate
Summary A 27-week-old infant developed symptoms of bowel obstruction when full enteral feeds were started. Laparotomy revealed strictures in the ascending and proximal transverse colon. Right hemicolectomy was performed. Histological examination of the resected large bowel demonstrated the presence of Cytomegalovirus inclusion bodies. Cytomegalovirus infections of the gut are extremely rare in neonates. This case report alerts neonatologists and microbiologists to consider Cytomegalovirus infection as a possible cause of bowel obstruction and necrotising enterocolitis like symptoms. ª 2006 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
Case report A female infant weighing 490 g was delivered by caesarian section at 27 weeks and 2 days of gestation prior to the onset of labour because of intra-uterine growth retardation, oligohydramnios, absent end-diastolic flow and deterioration in the cardiotocograph. Her mother was a heavy smoker and the placenta showed an area of infarct. She was born in good condition, with apgar scores of
* Corresponding author. þ44 2920 766462. E-mail address: [email protected] (A. Shetty).
9 at 1 min and 5 min. She was intubated and ventilated for 24 h and then changed to continuous positive airway pressure (CPAP) ventilation but did not require ionotropic support. She received parental nutrition and was not fed enterally for 5 days. Feeds were introduced gradually with frozen maternal milk and she was fully enterally fed by day 17 with 165 ml/kg/day. Despite three episodes of abdominal distension, which were managed conservatively, she remained well. Feeds were suspended during one episode for 1 h and reintroduced at 1 ml/h going up to full feeds within a day. On day 36 of life she developed acute abdominal distension with bilious aspirate. She became pale
0163-4453/$30 ª 2006 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2006.03.027
e38 and mottled, tachycardic with temperature instability and delayed capillary refill time of 3e4 s. Blood pressure remained stable. C reactive protein (CRP) was raised at 110 mg/L. The total white cell count was 2.4 109 per litre with a neutrophil count of 0.93 109 per litre and a lymphocyte count of 0.83 109 per litre. Abdominal radiography showed dilated loops of small bowel. Transfer to a tertiary neonatal unit was arranged for surgical opinion. On arrival at the specialist unit she was intubated and ventilated. Cefotaxime, vancomycin and metronidazole were commenced and enteral feeds were stopped. Total parenteral feeds were initiated. She required volume expansion with fluid boluses but inotropic support was not needed. Blood and urine cultures were negative. Two attempts to reintroduce enteral feeds failed as the abdominal distension worsened and nasogastric aspirates increased. The first attempt was on day 46 of life and the second on day 56 of life. Barium enema did not show any abnormality but barium meal and follow through demonstrated possible small bowel stricture. Laparotomy performed on day 65 revealed a normal small bowel with stricture in the ascending and proximal transverse colon. One loop of jejunum was adherent to the ascending colon. Right hemicolectomy was performed. Pathological examination showed inflamed, ulcerated caecum and colon, with an area of full thickness necrosis. The small bowel was distended. Numerous Cytomegalovirus (CMV) inclusion bodies were present throughout the inflamed area. Inflammatory changes extended throughout the resected gut extending into the margins. This was confirmed by immunohistochemistry (Fig. 1). Her
Figure 1 Immunohistochemistry of the large bowel revealing CMV.
A. Shetty et al. urine was positive for CMV by real time polymerase chain reaction (PCR) on the light cycler. This was after 10 weeks of age. There was no other evidence of CMV infection and cranial ultrasonography was normal. Maternal serology was positive for CMV IgG but negative IgM on both antenatal and postnatal specimens. The patient made a good recovery and was transferred back to the referring hospital after 56 days in the specialist unit.
Discussion Cytomegalovirus is an important cause of gastrointestinal symptoms in immunocompromised patients, especially patients infected with Human Immunodeficiency Virus (HIV). Cases of CMV gastrointestinal infections are extremely rare in neonates. There are a few case reports in the literature of CMV causing diarrhoea, colonic dysmotility and rectal bleeding in neonates.1e3 CMV causing colonic stricture has been described in only one previous case.4 Another report describes CMV-associated necrotising enterocolitis in a preterm twin after breast feeding.5 Infection in the neonate can be congenital or postnatal. Congenital infection occurs due to primary CMV infection or reactivation of the virus in the mother. Perinatal infection can occur during delivery. Postnatal infection occurs most often from ingested breast milk or blood transfusions with CMV positive blood. Our patient had caesarean section prior to the onset of labour hence it is unlikely to have been infected perinatally. The infant had 16 transfusions but all blood products were screened for CMV and leukocyte depleted. The infant did not show features of congenital CMV but this does not rule out congenital infection, as only 5% of babies infected at birth are symptomatic. Maternal breast milk is another likely source of infection. A study by Hamprecht et al. showed that 22% of infants exposed to CMV infected milk acquired the infection.6 Another study by Sharland et al. found that only 5% of infants were infected when fed with CMV positive milk.7 In this study the milk was frozen at 20 C prior to use whenever possible. Studies have shown that freezing milk reduces CMV infectivity of milk by greater than 90%.8,9 In our case the baby was fed expressed breast milk that was frozen. Our hypothesis is that the infant may have been infected in utero as a result of reinfection. This case provides strong evidence that CMV infection can cause bowel stricture and necrotising enterocolitis like symptoms and extends the spectrum of CMV infection in neonates.
Cytomegalovirus in a premature infant
References 1. Quiros-Tejeira RE, Ament ME, Rivera-Penera T, Cortina G, Vargas JH. Cytomegalovirus enterocolitis in an immunocompetent infant host: another cause of treatable intractable diarrhoea in infancy. Journal of Pediatric Gastroenterology and Nutrition 1999;29(1):86e90. 2. Dimmick JE, Boye KE. Cytomegalovirus infection of the bowel in infancy: pathogenetic and diagnostic significance. Pediatric Pathology 1984;2:95e102. 3. Hinds R, Brueton MJ, Francis N, Fell JM. Another cause of bloody diarrhoea in infancy: cytomegalovirus colitis in an immunocompetent child. Journal of Paediatric Child Health 2004;40:581e2. 4. Fournier V, Gallet S, Rebaud P, Bouvier R, Dutruge J. Enterocolite ulcero-necrosante: discussion du role du cytomegalovirus. A propos d’une observation. Pediatrie 1989;44:189e92.
e39 5. Gessler P, Bischoff GA, Wiegand D, Essers B, Bossart W. Cytomegalovirus-associated necrotising enterocolitis in a preterm twin after breastfeeding. Journal of Perinatology 2004;24: 124e6. 6. Hamprecht K, Maschmann J, Vochem M, Klaus D, Speer C, Jahn G, et al. Epidemiology of transmission of cytomegalovirus from mother to preterm infant by breastfeeding. Lancet 2001;357:513e8. 7. Sharland M, Khare M, Bedford-Russel. Prevention of postnatal cytomegalovirus infection in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2002; 86:F140. 8. Friis H, Andersen H. Rate of inactivation of cytomegalovirus in raw banked milk during storage at 20 C and pasteurisation. BMJ 1982;285:1604e5. 9. Dworsky M, Stagno S, Pass R, Cassady G, Alford C, et al. Persistence of cytomegalovirus in human milk after storage. The Journal of Pediatrics 1982;101:440e3.
www.elsevierhealth.com/journals/jinf
CASE REPORT
Cytomegalovirus: A cause of colonic stricture in a premature infant Anjali Shetty a,*, Rosemary Barnes a, Ed Lazda b, Cora Doherty c, Nicola Maxwell c a
University Hospital of Wales, Microbiology, Heath Park, Cardiff, United Kingdom University Hospital of Wales, Histopathology, Heath Park, Cardiff, United Kingdom c University Hospital of Wales, Neonatology, Heath Park, Cardiff, United Kingdom b
Accepted 21 March 2006 Available online 9 May 2006
KEYWORDS Cytomegalovirus; Neonate
Summary A 27-week-old infant developed symptoms of bowel obstruction when full enteral feeds were started. Laparotomy revealed strictures in the ascending and proximal transverse colon. Right hemicolectomy was performed. Histological examination of the resected large bowel demonstrated the presence of Cytomegalovirus inclusion bodies. Cytomegalovirus infections of the gut are extremely rare in neonates. This case report alerts neonatologists and microbiologists to consider Cytomegalovirus infection as a possible cause of bowel obstruction and necrotising enterocolitis like symptoms. ª 2006 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
Case report A female infant weighing 490 g was delivered by caesarian section at 27 weeks and 2 days of gestation prior to the onset of labour because of intra-uterine growth retardation, oligohydramnios, absent end-diastolic flow and deterioration in the cardiotocograph. Her mother was a heavy smoker and the placenta showed an area of infarct. She was born in good condition, with apgar scores of
* Corresponding author. þ44 2920 766462. E-mail address: [email protected] (A. Shetty).
9 at 1 min and 5 min. She was intubated and ventilated for 24 h and then changed to continuous positive airway pressure (CPAP) ventilation but did not require ionotropic support. She received parental nutrition and was not fed enterally for 5 days. Feeds were introduced gradually with frozen maternal milk and she was fully enterally fed by day 17 with 165 ml/kg/day. Despite three episodes of abdominal distension, which were managed conservatively, she remained well. Feeds were suspended during one episode for 1 h and reintroduced at 1 ml/h going up to full feeds within a day. On day 36 of life she developed acute abdominal distension with bilious aspirate. She became pale
0163-4453/$30 ª 2006 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2006.03.027
e38 and mottled, tachycardic with temperature instability and delayed capillary refill time of 3e4 s. Blood pressure remained stable. C reactive protein (CRP) was raised at 110 mg/L. The total white cell count was 2.4 109 per litre with a neutrophil count of 0.93 109 per litre and a lymphocyte count of 0.83 109 per litre. Abdominal radiography showed dilated loops of small bowel. Transfer to a tertiary neonatal unit was arranged for surgical opinion. On arrival at the specialist unit she was intubated and ventilated. Cefotaxime, vancomycin and metronidazole were commenced and enteral feeds were stopped. Total parenteral feeds were initiated. She required volume expansion with fluid boluses but inotropic support was not needed. Blood and urine cultures were negative. Two attempts to reintroduce enteral feeds failed as the abdominal distension worsened and nasogastric aspirates increased. The first attempt was on day 46 of life and the second on day 56 of life. Barium enema did not show any abnormality but barium meal and follow through demonstrated possible small bowel stricture. Laparotomy performed on day 65 revealed a normal small bowel with stricture in the ascending and proximal transverse colon. One loop of jejunum was adherent to the ascending colon. Right hemicolectomy was performed. Pathological examination showed inflamed, ulcerated caecum and colon, with an area of full thickness necrosis. The small bowel was distended. Numerous Cytomegalovirus (CMV) inclusion bodies were present throughout the inflamed area. Inflammatory changes extended throughout the resected gut extending into the margins. This was confirmed by immunohistochemistry (Fig. 1). Her
Figure 1 Immunohistochemistry of the large bowel revealing CMV.
A. Shetty et al. urine was positive for CMV by real time polymerase chain reaction (PCR) on the light cycler. This was after 10 weeks of age. There was no other evidence of CMV infection and cranial ultrasonography was normal. Maternal serology was positive for CMV IgG but negative IgM on both antenatal and postnatal specimens. The patient made a good recovery and was transferred back to the referring hospital after 56 days in the specialist unit.
Discussion Cytomegalovirus is an important cause of gastrointestinal symptoms in immunocompromised patients, especially patients infected with Human Immunodeficiency Virus (HIV). Cases of CMV gastrointestinal infections are extremely rare in neonates. There are a few case reports in the literature of CMV causing diarrhoea, colonic dysmotility and rectal bleeding in neonates.1e3 CMV causing colonic stricture has been described in only one previous case.4 Another report describes CMV-associated necrotising enterocolitis in a preterm twin after breast feeding.5 Infection in the neonate can be congenital or postnatal. Congenital infection occurs due to primary CMV infection or reactivation of the virus in the mother. Perinatal infection can occur during delivery. Postnatal infection occurs most often from ingested breast milk or blood transfusions with CMV positive blood. Our patient had caesarean section prior to the onset of labour hence it is unlikely to have been infected perinatally. The infant had 16 transfusions but all blood products were screened for CMV and leukocyte depleted. The infant did not show features of congenital CMV but this does not rule out congenital infection, as only 5% of babies infected at birth are symptomatic. Maternal breast milk is another likely source of infection. A study by Hamprecht et al. showed that 22% of infants exposed to CMV infected milk acquired the infection.6 Another study by Sharland et al. found that only 5% of infants were infected when fed with CMV positive milk.7 In this study the milk was frozen at 20 C prior to use whenever possible. Studies have shown that freezing milk reduces CMV infectivity of milk by greater than 90%.8,9 In our case the baby was fed expressed breast milk that was frozen. Our hypothesis is that the infant may have been infected in utero as a result of reinfection. This case provides strong evidence that CMV infection can cause bowel stricture and necrotising enterocolitis like symptoms and extends the spectrum of CMV infection in neonates.
Cytomegalovirus in a premature infant
References 1. Quiros-Tejeira RE, Ament ME, Rivera-Penera T, Cortina G, Vargas JH. Cytomegalovirus enterocolitis in an immunocompetent infant host: another cause of treatable intractable diarrhoea in infancy. Journal of Pediatric Gastroenterology and Nutrition 1999;29(1):86e90. 2. Dimmick JE, Boye KE. Cytomegalovirus infection of the bowel in infancy: pathogenetic and diagnostic significance. Pediatric Pathology 1984;2:95e102. 3. Hinds R, Brueton MJ, Francis N, Fell JM. Another cause of bloody diarrhoea in infancy: cytomegalovirus colitis in an immunocompetent child. Journal of Paediatric Child Health 2004;40:581e2. 4. Fournier V, Gallet S, Rebaud P, Bouvier R, Dutruge J. Enterocolite ulcero-necrosante: discussion du role du cytomegalovirus. A propos d’une observation. Pediatrie 1989;44:189e92.
e39 5. Gessler P, Bischoff GA, Wiegand D, Essers B, Bossart W. Cytomegalovirus-associated necrotising enterocolitis in a preterm twin after breastfeeding. Journal of Perinatology 2004;24: 124e6. 6. Hamprecht K, Maschmann J, Vochem M, Klaus D, Speer C, Jahn G, et al. Epidemiology of transmission of cytomegalovirus from mother to preterm infant by breastfeeding. Lancet 2001;357:513e8. 7. Sharland M, Khare M, Bedford-Russel. Prevention of postnatal cytomegalovirus infection in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 2002; 86:F140. 8. Friis H, Andersen H. Rate of inactivation of cytomegalovirus in raw banked milk during storage at 20 C and pasteurisation. BMJ 1982;285:1604e5. 9. Dworsky M, Stagno S, Pass R, Cassady G, Alford C, et al. Persistence of cytomegalovirus in human milk after storage. The Journal of Pediatrics 1982;101:440e3.