Journal of Infection (I99o) zo, 59-63
CASE REPORT Early-onset neonatal pneumococcal
s e p s i s in s i b l i n g s
E. D. Wright,*~ J. E. Lortant and R. M. Perinpanayagam*
* Department of Microbiology, Queen Mary's University Hospital, Roehampton, London SWI 5 5PN and t Department of Chemical Immunology, Westminster Hospital, London S W I P 2AP, U.K. Accepted for publication 24 May I989 Summary The case of a woman who in two successive pregnancies produced premature infants affected by early-onset Streptococcus pneumoniae type 8 sepsis is described. Low maternal levels of pneumococcal IgG antibodies were demonstrated after the second delivery, and vaccination with 'Pneumovax' produced a rise in antibody levels. Attention is drawn to the similarity between early-onset pneumococcal neonatal sepsis and group B streptococcal sepsis. Mothers of infants affected by early-onset pneumococcal sepsis who have low pneumococcal antibody levels run the risk of subsequent babies being similarly affected and vaccination should be considered to prevent recurrence.
Introduction Unlike the group B streptococcus (GBS) Streptococcus pneumoniae is a rare commensal of the genital tract. However, early-onset pneumococcal infection in neonates resembling G B S disease has been described. 1-3 An i m p o r t a n t risk factor for neonatal G B S infection is a low maternal level of specific I g G antibodies to bacterial carbohydrate antigens particularly of the I g G 2 subclass. 4'a G B S septicaemia in siblings has been described G in which the m o t h e r had very low levels of T y p e Ia and T y p e I I I G B S antibodies in both pregnancies, exemplifying h o w this immunological risk factor can cause recurrent problems. W e describe here an analogous case, that of a w o m a n with low levels of pneumococcal antibodies whose two successive pregnancies ended with p r e m a t u r e labour associated with genital tract colonisation with S. pneumoniae type 8 and early-onset neonatal pneumococcal infection.
Case report T h e patient was a 3o-year-old w o m a n with a history of cervical cone biopsy for carcinoma in situ ( C I N ii-iii) 2 years earlier. She was otherwise fit and well. H e r first pregnancy was uneventful until 31 weeks w h e n she complained of a vaginal discharge. N o abnormality was seen on examination and a swab was Address correspondence to: Dr E. D. Wright, Department of Microbiology, Worthing Hospital, Park Avenue, Worthing, West Sussex B N I I 2DH, U.K. oI63-4453/90/010o59+o5 $02.00/0
© I99o The British Society for the Study of Infection
E.D. W R I G H T E T A L .
not taken at that time. She was treated with topical clotrimazole because yeasts had been seen in a cervical smear taken at 17 weeks. At 33 weeks she was admitted following a spontaneous rupture of membranes (SROM) and a high vaginal swab (HVS) taken before delivery revealed a heavy pure growth of S. pneumoniae type 8 with many pus cells. T h e liquor was not noted to be foul or purulent and she was apyrexial during labour. Because of a history of penicillin allergy she was given erythromycin for 7 days after delivery. Her postnatal examination revealed a chronically inflamed endocervical polyp which was treated surgically. First neonatal history Two days after admission for SROM, a male infant weighing 1"73 kg was delivered by Andersens forceps after a 5 h 45 min labour. At birth his condition was poor and intubation was necessary for recurrent apnoea. Clinical dysmorphism was noted and trisomy 21 later confirmed. Blood cultures taken at delivery grew S. pneumoniae type 8 and the same organism was isolated from umbilical, ear and throat swabs taken immediately after delivery. Gastric aspirate and CSF samples were sterile. He was treated with intravenous penicillin 20o m g / k g / d a y and gentamicin 5 m g / k g / d a y for 7 days with clinical improvement. In the second week of life a pansystolic precordial m u r m u r was heard and atrio-ventricular septal defect was diagnosed. He developed refractory cardiac and respiratory failure and died 43 days after birth. Second pregnancy
Amniocentesis performed at 16 weeks revealed a foetal karyotype of 46XY. At 36 weeks spontaneous rupture of membranes again occurred and labour commenced 14 h later. After 4 h of labour foetal tachycardia was noted with T y p e 2 decelerations and an emergency Caesarian section was performed. Swabs from the endocervix and liquor taken prior to delivery grew S. pneumoniae type 8. T h e liquor did not appear purulent and she remained apyrexial throughout the peripartum period. Erythromycin and metronidazole were given during labour and continued for 8 days. T h e postnatal period was uneventful. Second neonatal history
T h e infant was a 2"5 kg male of 36 weeks maturity. Apgar scores were 6 at i min and 9 at 5 rain. Nose, throat and ear swabs taken from the infant at birth all grew S. pneumoniae type 8 but blood cultures and CSF were sterile. T h e baby developed a pyrexia of 38 °C on the second day after birth and his respiratory rate increased to 78 per minute. He was treated with intravenous penicillin 20o m g / k g / d a y and gentamicin 5 m g / k g / d a y for 7 days and made a good recovery. No abnormalities were detected on examination I week after discharge. Laboratory investigations
All S. pneumoniae isolates were serotyped at the Streptococcal Reference Laboratory, Central Public Health Laboratory, London. All were sensitive to
Neonatal pneumococcal sepsis in siblings
Table I Antibody titres in maternal serum to polyvalent pneumococcal vaccine Titres 14 m o n t h s post partum 2 n d delivery
Pneumococcal A n t i b o d y type IgA IgM IgGI IgG2 IgG3 IgG4
i week post partum 2nd delivery 8 > Io24 < 8 r6 < 8 < 8
Before Pneumovax < 8 512 < 8 64 < 8 < 8
i month after Pneumovax 8 > IO24 32 I28 < 8 < 8
Pooled n o r m a l human serum 32 256 i28 256 < 8 < 8
penicillin, tetracycline and erythromycin by the Stokes' method. 7 Maternal immunoglobulin levels (IgG, IgA, IgM, I g G I - 4 . ) were within the normal range. T h e titres of specific antibodies to pooled pneumococcal carbohydrate antigen (Pneumovax, T h o m a s M o r s o n Pharmaceuticals, which includes pneumococcal polysaccharide type 8) were measured by E L I SA and the results are shown in Table I together with those of pooled normal h u m a n serum. Most of the anti-pneumococcal antibodies present immediately following the second delivery were of the I g M class with very little IgG, particularly IgG2, detected. T h e m o t h e r was vaccinated with ' P n e u m o v a x ' to determine whether she could m o u n t an adequate I g G antibody response which might prevent recurrence of neonatal sepsis in further pregnancies. Titres before and after vaccination (Table I) indicate that she responded to immunisation, although the IgG2 titre did not reach that of pooled normal h u m a n serum by I m o n t h post-vaccination. Discussion
Streptococcus pneumoniae is a relatively rare cause of early-onset neonatal sepsis but, like the Group B streptococcus, it has the potential to cause lifethreatening infection. Neonatal infections caused by these organisms have c o m m o n clinical and epidemiological features. Both are acquired from the colonised maternal genital tract, and prematurity and prolonged rupture of membranes are risk factors for neonatal infection. T h e IgG2 subclass of immunoglobulins is involved in the response to carbohydrate antigen 8 and it has been shown that mothers of GBS-infected infants have a poor IgG2 response to various bacterial carbohydrate antigens including those of pneumococci. 5 It is not therefore unexpected to find such a deficiency in this case of early-onset pneumococcal infection affecting two successive pregnancies. T h e basis for the defect is not understood, although genetic factors are
E. D. W R I G H T E T A L .
clearly important. In mice the i m m u n e response to pneumococcal polysaccharide type x4 is controlled by loci closely linked to the Ig allotype loci. 9 G r u b b e t al. *° have shown an abnormal distribution of G m allotypes in mothers of infants with GBS sepsis. As with early-onset GBS sepsis, the subsequent pregnancies of mothers of infants affected by early-onset pneumococcal sepsis should be monitored carefully and intrapartum penicillin or ampicillin given if prenatal cultures are positive and prolonged labour a n d / o r premature rupture of membranes occur. In such cases where maternal pneumococcal antibody levels can be shown to be low, vaccination with ' P n e u m o v a x ' should be considered in an attempt to prevent recurrent sepsis in subsequent pregnancies. Post-vaccination titres especially of IgGz subclass should be estimated to assess immunity. T h e patient described here produced both I g M and IgG2 responses to vaccination. Further information is required to determine if the IgG2 response m o u n t e d by susceptible mothers, such as described here, is sustained and is protective in later pregnancies. Clinical pneumococcal infection in a m o t h e r should alert clinicians to the likelihood of inadequate immunity and possible late-onset sepsis in the infant. Shaw et al.** have described fatal pneumococcal infection in both m o t h e r and 6-week-old son, and suggested that in such cases the infant should receive penicillin prophylaxis followed by a period of microbiological surveillance. Since early-onset sepsis caused by both GBS and S. pneumoniae have similar risk factors including maternal IgGz deficiency, it is possible that a susceptible m o t h e r might have pregnancies affected by either or both organisms. Maternal genital tract colonisation is a major factor in the aetiology of earlyonset neonatal sepsis and it is of interest that this patient was colouised with the same serotype of pneumococcus in both pregnancies. Endocervical and high vaginal swabs taken 9 weeks after her second delivery failed to grow S. pneumoniae. Streptococcus pneumoniae is a rare vaginal commensal; the normal vaginal flora and hormonal environment, the adhesive capacity of pneumococci to genital tract epithelial cells and immunological mucosal defence mechanisms are all likely to influence colonisation. Studies of pneumococcal adherence in otitis media indicate that nasopharyngeal isolates from patients with otitis media adhere more strongly to oropharyngeal epithelial cells than isolates from patients with septicaemia or meningitis. 12 Adhesion of pneumococci to genital tract epithelial cells in non-pregnant and pregnant women has not been examined. Absence of mucosal antibody in patients with hypogammaglobulinaemia could contribute to persistent colonisation and predisposition to pneumococcal infection. This patient had neither I g G nor IgA deficiency and her medical history indicated no tendency for either systemic or surface-related recurrent infections. A rare case of secretory IgA deficiency has been described in which the serum IgA concentration was normal but IgA was absent from secretions. .3 This patient had suffered from chronic diarrhoea and intestinal candidiasis since ceasing to breast feed. Microbiologists, obstetricians and paediatricians must be aware of the potential of S. pneumoniae to cause serious early-onset infection in susceptible infants. T h e finding of this organism in peripartum HVS, liquor or neonatal
Neonatal pneumococcal sepsis in siblings
screening specimens should alert clinicians to the possibility of sepsis and appropriate monitoring and therapeutic measures should be taken. (We wish to thank D r R. Ballard and D r B o m m e n for p e r m i s s i o n to r e p o r t this case and M r s K. W i l s o n for t y p i n g the m a n u s c r i p t . )
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