A 23 year old HIV-seronegative mother (G2 P2 -1), gave birth to monochorionic, diamniotic twin infants.
The mother had a history of miscarriage at 23 weeks (unknown cause). She was HIV seronegative. She had booked late and was 24 weeks by late ultrasound. The twin pregnancy was treated as an inevitable miscarriage when she went into preterm labour. The mother did not receive intrapartum antibiotics and there was no fetal monitoring.
Twin A was born with Apgars of 8,9 and 9. No resuscitation was necessary. Birth weight was 700g. Liquor was clear. She was assessed as being 27 weeks according to Ballard score and commenced on CPAP. No surfactant was given. Penicillin and gentamicin were commenced according to the protocol for preterm infants. Initial blood tests revealed:
WCC = 5.18 x 109/L; Hb = 15.1 g/dl; plt = 266 x 109/L
C- reactive protein (CRP) = 12 on day 1 and repeat after 12 hours was < 4.
Blood culture was negative after 5 days - Antibiotics were stopped after 3 days.
On day 20 she received ibuprofen to close a patent ductus arteriosus.
On day 22 (gestational age 30 weeks and 1 day) she developed recurrent apnoea.
WCC= 4.27 x 109/L
Neutrophils were 12% with absolute count of 0.51 per mm3
Hb = 11.6 g/dl, nucleated RBCs 18 x 109/L
Plt = 436 x 109 /L
CRP was 114.
She was started on meropenem and vancomycin but was too unstable for lumbar puncture.
Within 6 hours the blood culture grew Gram positive cocci in chains, sensitive to penicillin, ampicillin and erythromycin.
Twin A demised on day 24.
X ray of Twin A
Twin B had Apgar scores of 3, 5 and 8. Birth weight was 820g.
She was estimated to be 29 weeks by Ballard score.
After initial resuscitation she was started on CPAP.
First 2 weeks of life were uneventful. She also received penicillin and gentamicin for the first 3 days. These were stopped after CRP was < 4 and initial blood culture was negative.
On day 17 Twin B started to desaturate.
WCC = 13.8 x 10 9/L
Hb = 13.8 g/dl; platelets =323 x 109/L.
CRP was < 4
Meropenem was started, but stopped after 4 days when the blood culture came back negative.
3 days later a repeat crp was < 4.
On day 25 Twin B developed persistent tachycardia. Penicillin was started. This was just after Twin A had demised.
Penicillin stopped after 2 days as the infant was asymptomatic, CRP was < 4 and blood culture was negative.
On day 33 Twin B again developed desaturations and was admitted to NICU.
WCC= 3.6 x 109/L, neutrophil count = 64%
Hb = 9.2g/dl; Plt = 300 x 109 /L
Blood culture grew Gram positive cocci in chains after 9 hours sensitive to penicillin, ampicillin and erythromycin.
Lumbar puncture : CSF was yellow. P=0; L = 5; RBC= 0. No growth.
Twin B was treated for 14 days with Penicillin. On day 51 Twin B deteriorated again (5 days after stopping penicillin) and was started on meropenem and vancomycin. Blood culture again grew Gram positive cocci in chains sensitive to penicillin, ampicillin and erythromycin. The culture was positive within 4.5 hours suggesting a high bacterial load.
Additional investigations and information: Maternal breast milk was sent twice for culture and was negative. Maternal and Twin B throat swabs were negative for group B streptococcus Mother did not have mastitis.
Xray of Twin B
Both infants had Group B Streptococcus on blood culture.
Question 1: What are the different clinical presentations of Group B Streptococcal infection in infants?
Answer to Q1
Group B Streptococcus or Streptococcus agalactiae can present as early onset disease (EOD) between 0-6 days or as late onset disease (LOD) in young infants between 7-90 days.
EOD is caused by ascending infection; the infant usually aspirates infected amniotic fluid and develops symptoms of pneumonia shortly after birth. Other common presentations are septicaemia and meningitis. GBS can also present with a focal pathology such as cellulitis, adenitis, osteomyelitis or arthritis. Infants with LOD GBS have similar clinical presentations.
Although EOD has a higher mortality, LOD often results in long term sequelae such as cognitive defects, deafness and blindness.
In America and Europe EOD has been reduced by the introduction maternal screening for GBS and intrapartum antibiotic prophylaxis (IAP), but incidence of LOD remains unchanged (1).
African data is limited as GBS is often under reported but is nevertheless a major cause of morbidity and mortality.
Common serotypes reported in South Africa are Ia, Ib and III with serotype III reported as being the most pathogenic strain.(2). A recent systematic review and meta-analysis of GBS found that in low- and high-income countries, the main serotypes are Ia, Ib, II, III and V, thus a vaccine including these serotypes could prevent invasive GBS (3).
Question 2: What are the risk factors and modes of transmission for late onset invasive Group B Streptococcus?
Answer to Q2
Mode of transmission
While EOD GBS is always transmitted vertically, LOD GBS can be acquired from other sources. Infection from maternal colonization with GBS is one mode of transmission; one study showed that 50% of infants that developed LOD GBS were colonized at birth and their mothers were colonized with the identical serotype (4). In infants whose mothers are not colonized, it is often difficult to establish the route of infection. Nosocomial transmission has been reported (5,6). Case reports have identified breast milk as a source of infection and horizontal transmission after the perinatal period may occur (7-10).
Prematurity is the major risk factor for LOD GBS (11).
Although maternal colonization is a risk factor for LOD GBS as described above (11), it is not as strongly associated with risk as is EOD. In the United States African Americans have higher risk of LOD, with black infants having a three times higher incidence of late onset GBS (12). A recent paper showed a high incidence of GBS in HIV-exposed but un-infected infants with more LOD than in unexposed infants (5 out of 6 episodes were LOD compared with 2 out of 16 episodes in unexposed infants)(13). However other studies from Brazil, Zimbabwe and Malawi suggest that maternal colonization by GBS is not increased in those that are HIV-infected(14 - 17). The Brazilian study found no cases of LOD GBS in HIV-infected women, but there was no comparator group, limiting interpretation of the findings (17).
Question 3: What are the possible causes of recurrent invasive Group B streptococcus infection and what can be done to prevent it?
Answer to Q3
Recurrence of GBS disease was first reported in the mid seventies (18,19,20). DNA restriction enzyme analysis has allowed differentiation between infection with a ‘new’ GBS strain and the same strain. In a previous case series it was found that 5 out of 6 infants infected with the same serotypes had genetically identical GBS isolates suggesting persistent mucosal colonization may be more common than infection with a new strain (21).
Rifampicin has been used to clear persistent mucosal colonization but has limited efficacy (22) As seen in our case report penicillin also fails to eradicate persistent colonization (23).
Question 4: Is there evidence that twins are at greater risk of invasive GBS?
Answer to Q4
Twin pregnancy has been reported as an uncommon risk factor for invasive GBS disease (24,25,26) despite vaginal GBS rates having been shown to be similar in twin and singleton pregnancies (25). Some guidelines recommend investigation of the other twin and commencement of empiric antibiotics until cultures become available (27). The relative risk of a twin having invasive GBS if the other twin is infected has been calculated as being as high a 25 times that of an infant without an infected twin (28). Twins are likely to share predisposing factors for LOD such as a low concentration of maternal IgG specific antibody for capsular polysaccharide that is available for placental transport, decreased placental transport of maternal IgG if they are born before 34 weeks gestation and the same bacterial virulence of a particular strain of GBS (if they are infected with the same strain)(29).
GBS can be recurrent and can occur soon after a full course of penicillin. Twins have increased risk of GBS. Prematurity is the major risk factor for LOD.
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