Chapter 10. Infection
Congenital infections with organisms that may have little effect on an adult or older child can have a devastating effect on the fetus and infant, resulting in profound long-term damage. The commonest cause of congenital infection is cytomegalovirus affecting 0.5–3% of live births worldwide. In very low birth weight infants who need prolonged intensive care, rates of culture-proven infection of up to 30% have been quoted, with mortality rates that are equally high. Neonatal units are busy and as they become busier both time and staffing constraints lead to an increase in nosocomial infections.
Questions in this chapter will cover different aspects of congenital infections, the presentation of sepsis, prevention of infection and other common situations such as contact with chickenpox on the neonatal unit.
QUESTION 1
Which of the following statements about cytomegalovirus (CMV) are correct (answer true or false)?
i) CMV is an RNA virus
ii) It is the most common intra-uterine infection
iii) Congenital CMV can be caused by maternal primary infection or reactivation and both are of the same severity
iv) The incidence of primary CMV infection acquired during pregnancy is 5–10%
v) Primary CMV infection is associated with a 40% risk of congenital CMV infection
vi) At least 50% of infected infants will show clinical signs at birth
vii) There is a 20% mortality associated with symptomatic congenital CMV
viii) Infants can become infected by breast feeding if the mother is seropositive.
QUESTION 2
You are called to counsel a mother who is 31 weeks gestation. The baby was noted to be small on scans. Karyotyping from the amniotic fluid is normal and the fluid is positive for CMV by PCR. The fetus is noted to have unilateral ventriculomegaly.
i) What other abnormalities should be looked for on the antenatal scans?
ii) Which of the following symptoms could be present in the newborn period? Choose six correct answers.
a. Seizures
b. Hepatosplenomegaly
c. Thrombocytopenia
d. Unconjugated hyperbilirubinaemia
e. Chorioretinitis
f. Cataracts
g. Defective enamelisation
h. Inguinal hernia.
iii) What is the likely prognosis if the baby shows symptoms at birth?
iv) If the baby is asymptomatic at birth, what is the likely prognosis?
v) Which is the preferred method for testing for congenital CMV? Choose one answer.
a. Detection of pp65 antigen in white blood cells
b. Virus isolation from placenta
c. PCR assay of urine
d. Serology testing for IgG and IgM
e. Histology of skin biopsy.
vi) What action would you take after birth to confirm the diagnosis of congenital CMV and over what time scale?
The baby’s investigations support the diagnosis of congenital CMV. On examination, the baby has a large liver and spleen, thrombocytopenia and imaging reveals intracranial calcification.
vii) What treatment options are available?
QUESTION 3
Regarding parvovirus B19, which of the following statements are correct?
i) It is a large double stranded DNA virus
ii) It is a small single stranded DNA virus
iii) It replicates in rapidly dividing cells
iv) Approximately 25% of adults show evidence of a previous infection
v) A rash and arthralgia occur in the second phase of the illness. At this point, the child is still infectious
vii) If parvovirus B19 infection occurs during pregnancy, the majority of fetuses will be affected
viii) The outcome of the fetus depends on the point at which the infection occurred in pregnancy.
QUESTION 4
The following features are typically associated with which intrauterine infection – hydrocephalus, epilepsy, cerebral calcification and chorioretinitis. Choose the best answer.
i) Congenital CMV
ii) Congenital toxoplasmosis
iii) Congenital Epstein–Barr virus
iv) Congenital varicella
v) Congenital rubella
vi) Congenital herpes
vii) Congenital TB.
QUESTION 5
Which of the following statements are true of toxoplasmosis?
i) The risk of congenital infection remains constant throughout pregnancy
ii) The risk of congenital infection is up to 90% in the third trimester
iii) Congenital infection is more severe if maternal infection is acquired in the third trimester
iv) In the UK, about 60% of women are sero-positive
v) Congenital infection occurs in 1 in 100 exposed babies
vi) Increasing gestational age at seroconversion is associated with an increased risk of mother-to-child transmission
vii) CSF will show a lymphocytosis
viii) Toxoplasmosis cannot be treated
ix) If diagnosed antenatally in the first trimester the mother can be treated with pyrimethamine and sulfadiazine to decrease the risk of fetal infection
x) If there are no eye signs within the first year of birth, the infant is unlikely to develop ocular problems.
QUESTION 6
You are called to the postnatal ward to review a baby who is 8 hours old.
The midwife reports that the baby is not feeding well. His mother says he tried to feed after birth but now is not interested. On examination, the infant looks pale, and feels slightly floppy. He is mottled with cool peripheries and has a heart rate of 160 bpm and mild recession. He has normal heart sounds, and both femoral pulses can be felt.
i) What is your first management step?
ii) What questions if any do you ask the mother?
iii) List five investigations you should carry out.
iv) What other investigations may be useful?
v) What is your next step in managing this baby?
The results of the initial investigations are obtained and shown below:
| Hb | 14.7 g/dL |
| WBC | 21.4×10 9/L |
| Neut | 1.7×10 9/L |
| Platelets | 104 × 10 9/L |
| CRP | 94 mg/L |
Urine SPA sample – no cells, no organisms seen
Chest x-ray shows a diffuse, fine, reticulogranular pattern, much like that seen in RDS.
The infant is breathing without ventilatory support with some low flow oxygen to maintain his saturations. He has had his first dose of antibiotics and is currently on maintenance fluid.
vi) What do you do now?
A lumbar puncture is carried out and the result is below:
| RBC | 18,000/mm 3 |
| WCC | 12/mm 3 |
| Protein | 2.5 g/L |
| Glucose | 1.4 mmol/L |
CSF is moderately blood stained
vii) What does this result mean?
Six hours later the infant is more symptomatic having frequent apnoeas and desaturations. He is intubated and ventilated. Repeat bloods show the following results:
| CRP | 120 mg/L |
| Platelets | 45×10 9/L |
| Neutrophils | 0.8×10 9/L |
There is a phone call from the microbiology department the following day saying the blood cultures are growing Group B Streptococcus. The infant’s CRP is now 40 mg/L, and his platelets have been stable above 100 after the platelet transfusion.
ix)
a. How will you modify your treatment, if at all?
b. How long will you treat the baby?
c. What will you tell the parents?
QUESTION 7
A baby is born at term by normal vaginal delivery with good Apgars requiring no resuscitation. Membranes were ruptured just prior to delivery, and the mother was well throughout pregnancy and labour. The mother is a primigravida. You receive a phone call from the midwife looking after the mother, when the baby is 12 hours old to say group B Streptococcus is growing from a maternal high vaginal swab. The mother wishes to go home.
What do you do? Choose the best answer.
i) Admit the baby to the NICU for observation
ii) Admit the baby to the NICU for observation and routine surface swabs
iii) Admit the baby to the NICU for a septic screen (blood cultures, FBC and CRP) and await results before considering antibiotics
iv) Admit the baby to NICU, perform septic screen and start antibiotics
v) Reassure and discharge home
vi) Allow to go home with instructions if the baby becomes unwell to seek medical advice
vii) Discuss with the mother and say that she must stay in and the baby must be observed for a further 24 hours
viii) Observe the baby for another 12 hours; allow to go home with instructions if the baby becomes unwell to seek medical advice.
QUESTION 8
You are working on the Neonatal Unit when one of the mothers tells you that her other child has been sent home from nursery with suspected chickenpox. The mother is unsure whether she has had chickenpox. The baby is now 5 days old, corrected gestational age 35 weeks and is well. The mother is also well.
What do you do? Choose the correct answer.
i) Reassure the mother that no treatment is needed
ii) Reassure mother but isolate baby in side room
iii) Check the mother and baby’s immune status and then give VZIG to both
v) Check the baby’s immune status and if negative give the baby VZIG
vi) Give the baby and mother VZIG
vii) Give the baby VZIG and aciclovir.
QUESTION 9
Which of the following organisms are known to commonly cause osteomyelitis? Choose four answers.
i) Bacillus fragilis
ii) Bacillus cereus
iii) Bacteroides fragilis
iv) Campylobacter jejuni
v) Haemophilus influenzae
vi) Proteus mirabilis
vii) Salmonella typhi
viii) Group B streptococcus (GBS)
ix) Staphylococcus aureus
x) Klebsiella
xi) Serratia marcescens.
QUESTION 10
Which of the following babies should receive hepatitis B immunoglobulin?
i) Mother is HBsAg negative and HBeAg negative
ii) Mother is HBsAg negative and HBeAg positive
iii) Mother is HBsAg positive and HBeAg negative
iv) Mother is HBsAg positive and HBeAg positive
v) Mother had acute hepatitis during pregnancy
vi) Mother where eAg and eAb status are unknown.
QUESTION 12
Which of the following are true of congenital rubella syndrome?
i) It is a notifiable disease
ii) Causes hydrocephalus
iii) Causes thymic hypoplasia
iv) Causes corneal opacity
v) Causes bony abnormalities
vi) Causes IUGR
vii) Causes microphthalmia
viii) Causes conductive deafness
ix) Causes PDA
x) Causes aortic stenosis
xi) Infection during the first 12 weeks of pregnancy results in congenital infection and/or miscarriage in all cases
xiii) The infant is extremely infectious in the immediate postnatal period but this is no longer a risk after the first 4 weeks of life
xiv) Rubella is increasing in the immigrant population.
QUESTION 13
You are called to see a baby after delivery. The mother has had routine booking bloods and serology. The results are as follows:
RPR reactive
TPHA reactive
Rubella immune
Hepatitis negative
i) What do these test show?
ii) What test do you carry out to confirm this?
The confirmatory test is also reactive.
iii) What do you do now? Name two things.
iv) Which one test would confirm a diagnosis of congenital syphilis?
v) If the test is negative, what does this show?
vi) What information do you need from the mother?
vii) What other test might be helpful in assessing the risk to the baby?
On examination the baby looks normal, the non-treponemal serologic titre is less than four times the maternal titre, and the mother had treatment 2 weeks ago.
viii) What do you do?
QUESTION 14
On your neonatal unit, three babies are found to be growing an Enterobacter with identical antibiotic resistance. It is the opinion of the microbiologists that these must have been transmitted by staff contact. It is their recommendation that the three infants are isolated and barrier nursed and that there is a serious review of infection control procedures.
Which of the following statements are true?
i) Infected infants should remain in the cots they currently occupy; all staff involved in the care of the baby should adopt barrier nursing procedures
ii) Wearing of sterile gloves avoids the need for repeated hand washing
iii) Infected babies may be nursed by the same member of staff as uninfected infants
v) Topical antibiotic ointment should always be used
vi) Use of separate gowns for each baby is an extremely important element of infection control
vii) Screening of all babies and all staff may be implicated
viii) Staffing levels are closely related to the incidence of nosocomial infection, as is the availability of hand washing facilities
ix) Units should be closed to all admissions as soon as the possibility of an outbreak is considered
x) Environmental screening is of no value
xi) Meticulous attention to hand hygiene is by far the most important element in reducing the spread of infection
xii) There is good evidence that standards of hand hygiene are normally very high in neonatal intensive care units
xiii) Soap and water hand wash is more effective than the use of alcohol-based hand rub
xiv) Topical cord care at birth has a major role in reducing the incidence of infection.
ANSWER 1
i) False – CMV is a DNA virus of the herpes virus group.
ii) True – it affects up to 2.5% of live born infants a year worldwide. In the UK the incidence is approximately 0.2%.
iv) False – the incidence is thought to be 1–4%.
v) True.2
vi) False – overall, only 10–15% of infected infants show clinical signs at birth but up to 90% of these will develop long-term sequelae. 3
vii) True – reports state mortality ranges between 10% and 30% although much higher in premature infants.
viii) True – in the postpartum period, mother to infant transmission can occur as up to 88% of seropositive mothers shed the virus into their milk. Approximately 50% of these infants will become infected. CMV excretion is usually the result of reactivation in a seropositive mother; most infants will not develop clinical signs due to the presence of maternally derived transplacental antibodies. This is usually a benign and asymptomatic infection.
ANSWER 2
i) Echogenic bowel, intracranial calcification, cortical dysplasia.
ii) Answers a, b, c, e, g and h are correct. Hepatosplenomegaly and petechiae secondary to thrombocytopenia are relatively common manifestations of congenital CMV in the neonatal period. Jaundice is also common but this is usually a conjugated hyperbilirubinaemia as CMV hepatitis can cause both intrahepatic and extrahepatic bile duct destruction. 4 Intracranial manifestations of congenital CMV are microcephaly and periventricular calcification where the infection has caused brain necrosis. Lissencephaly and polymicrogyria can be present depending on the timing of the infection, lissencephaly occurring with an earlier infection. Defective enamelisation occurs in 40% of symptomatic infants at birth and 5% of asymptomatic infants. Inguinal hernias can occur with congenital CMV in male infants although the reason for this is unclear.
iii) Up to 80% of symptomatic newborns will develop sequelae such as mental retardation, cerebral palsy, visual defects and sensorineural hearing loss. Symptoms at birth are associated with a worse prognosis. 5
iv) Up to 15% of infants who are asymptomatic at birth will have neurodevelopmental problems and sensorineural (SN) deafness. SN deafness is the most common abnormality seen in congenital CMV infection, occurring in 30–65% of symptomatic infants and up to 15% of asymptomatic infants. It usually develops after the newborn period and tends to be progressive. Cochlear implants have been used successfully.
v) Answer c is correct.
a. Detection of the pp65 antigen has been used to detect active infection in immunocompromised people but due to the large quantity of blood required this test is less useful in neonates. However a recent paper showed that high levels of pp65 antigen in the blood were seen in newborns that developed sequelae. 5 This test is very rarely used in the UK as it has been superseded by PCR.
b. High viral load in the urine is highly predictive of audiological impairment. 6
c. PCR is the gold standard for testing for congenital CMV.
d. A positive IgG reflects passage of maternal antibodies and therefore does not diagnose infection in the baby. Maternal IgG can persist up to 12 months. A positive IgM test does suggest congenital infection but both false positive and false negative results can occur. The test has a sensitivity of approximately 75%. With the availability of PCR, viral serology should not be used to diagnose congenital infection.
e. Skin biopsy – this is not used for CMV testing.
vi) PCR testing on a urine sample needs to be done within the first 3 weeks after birth. If the test is carried out after 3 weeks it is difficult to distinguish between a congenital, perinatal or postnatal infection. Infants infected at birth after exposure to infected secretions during delivery may start shedding virus by 3 weeks of age.
vii) There are currently a few antiviral chemotherapeutic agents, such as ganciclovir and foscarnet, that are available for treatment of serious, life-threatening or sight-threatening CMV in the immunocompromised patients. Cidofovir is also licensed for CMV retinitis. A randomised, controlled multicentre clinical trial investigated the use of ganciclovir for the treatment of infants with congenital CMV infection with evidence of CNS involvement. 7 Ganciclovir (or placebo) was given intravenously as an infusion every 12 hours for 6 weeks. The ganciclovir group were significantly more likely to have improved or normal hearing at 6 months of age compared to the placebo group. They also showed improvement in their liver function tests and head circumference. No change in mortality was demonstrated and currently there are no published data on long-term outcome. Ganciclovir is not thought to be beneficial for infants who show severe intracranial pathology antenatally. Several centres in the UK are using a six-week course of intravenous ganciclovir and then switching over to oral valganciclovir, with close monitoring of levels and viral load to assess response. The main side effects of ganciclovir are secondary to bone marrow suppression. Nigro8 described a study using CMV specific hyperimmune globulin and found that pregnant women whose amniotic fluid was CMV positive, and who were given passive immunisation, had a lower rate of congenital CMV when compared to a control group. There are currently no randomised trials looking at this preventative treatment.
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