Infectious disease and immunity

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16 Infectious disease and immunity

Richard Beach, Nandu Thalange

Introduction

The newborn infant is immunologically naive, protected only by its inheritance of maternal antibodies and its inexperienced immune system. Babies and toddlers have to acquire immunity to a whole range of infections which they do by catching one illness after another.

Immunization protects children from a range of deadly infections (see Chapter 1, p. 3 for UK immunization schedule), but a 4-year-old can still expect 6 to 10 illnesses per year – usually viral. Thus, infectious disease is ubiquitous in children. In many countries, diseases such as measles and gastroenteritis remain major causes of death, especially when combined with malnutrition.

The challenge for the doctor is to sort the benign and self-limiting viral infections from those few deadly infections, such as meningitis, septicaemia and pneumonia, which are rightly feared by parents and doctors alike.

History

Symptoms of infection are often non-specific, especially in the early stages. Parents may describe children as not like their normal selves, listless, lethargic or not feeding well. Use direct questions to tease out the timings of fever, rash and other symptoms. Where did the rash start? Has it changed? How did it spread? Reluctance to eat or drink may indicate a sore mouth or throat, and children may rub miserably at a sore ear. Do not forget that these diseases may be infectious so ask about family contacts and friends with similar symptoms.

Examination

Examining the febrile child with an acute illness is always a challenge but with patience and gentleness a full examination is possible. Examining the ears and mouth and throat is essential but best left until last as it often upsets the fractious toddler. Look carefully for a rash and check if it is purpuric.

Rashes are often the reason for seeking medical advice. Most are non-specific, blanching, maculopapular rashes of viral origin, typically varying over time. Rarely, such rashes are the first signs of serious illness, such as meningococcal septicaemia, so always recommend that parents return if they are concerned their child is deteriorating, and show them how to check for non-blanching spots with a glass tumbler.

Non-blanching rashes are highly concerning. Petechiae are less than 1 mm in diameter and may signify bacterial infection but are common in viral illnesses where observation for a minimum of 4 hours is recommended. When present in the distribution of the area drained by the superior vena cava, look for causes of raised intrathoracic pressure – principally prolonged coughing or vomiting. Purpura (spots greater than 1 mm) in a child who is unwell and who has a temperature should be taken as evidence of meningococcal septicaemia and treated as an emergency (see Appendix I, p. 288).

Palpate the lymph nodes and spleen. Check carefully for a stiff neck but do not forget that this sign may not be present in children less than 1 year old. Check vital signs carefully – capillary refill, pulse, blood pressure, temperature and respiratory rate. Septicaemia and shock may complicate acute infections. Remember that falling blood pressure is a late sign. A tachycardia should be a cause for concern – there must always be an explanation.

Investigations

A urine sample is always important but not always easy to collect (see Chapter 11, p. 118). Take swabs from vesicles, purulent lesions and weeping skin. There are different swabs and transport media for bacteria, viruses and Chlamydia – make sure that the right one is used.

A throat swab is sometimes useful in sore throats but always important in meningitis where growth correlates with cerebrospinal fluid (CSF) findings. Lumbar puncture is the gold standard test for diagnosing meningitis and should be considered whenever meningitis remains a possible diagnosis. There is a small but significant risk of coning (see Chapter 14, p. 188) if lumbar puncture is performed in acutely ill infants. In these circumstances, delayed lumbar puncture is safer (see Box 16.1).

Box 16.1

Contraindications to lumbar puncture

• Signs of raised intracranial pressure or depressed or abnormal conscious level

• Abnormal coagulation (platelets below 50 x 10⁹/L)

• Respiratory distress

• Shock or signs of poor perfusion

• Recent seizure (within 30 minutes) or prolonged seizure (over 30 minutes)

• Focal seizures or focal neurological signs

For lumbar puncture results and interpretation see meningitis, below.

Acute fever

It is often hard to be certain of the cause of infection in children who are acutely unwell. Are there signs of a serious infection? Check carefully for pneumonia and meningitis, or other features of sepsis such as impaired capillary refill, tachypnoea or tachycardia. In hospital practice it is usual to screen for any major infection. This septic screen usually includes blood culture, full blood count, ESR (erythrocyte sedimentation rate) or C-reactive protein (CRP), urine culture and a lumbar puncture. Collecting these samples before antibiotic administration improves the chances of growing an organism and clinching the diagnosis. Children screened for serious bacterial sepsis are usually, although not invariably, treated with antibiotics pending CSF and blood cultures.

Is there an upper respiratory tract infection? Otitis media and tonsillitis are very common, and it is crucial to look at the throat and ears carefully. Children with tonsillitis might appear surprisingly unwell. Think of urinary tract infection – collect a clean catch specimen for local and laboratory testing.

Is there a history of foreign travel? Infections such as malaria or viral haemorrhagic fevers may only become manifest after return to the UK.

If the child is not very ill, a wait-and-see approach is an acceptable policy. The rash in many viral infections may follow hours or days of fever.

Possible meningitis

Unconscious or drowsy children should be assumed to have meningitis or encephalitis. Irritability implies cerebral irritation and may be hard to distinguish from children who are simply feverish, frightened and miserable. A smile, some desultory play or even well-organized objection to examination is reassuring. Children with a high-pitched cry or who cannot be comforted are of concern. Seizures with a fever are usually febrile seizures in children aged 6 months to 5 years (see Chapter 14, p. 190) but meningitis, encephalitis and brain abscess may also cause seizures – especially in infants.

Case 16.1

A boy with meningitis

Faisal, a 15-year-old boy, presented with a 2-day history of sore throat, fever and headache. He was brought in by ambulance having suffered a generalized seizure at home. On examination he was drowsy and combative. His temperature was 38.5°C. He was well perfused with normal blood pressure and a pulse of 130 beats per minute. He had marked neck stiffness.

Investigation

In Case 16.1, the clinical diagnosis is meningitis. The likely causes are listed in Table 16.1. Early treatment may be life-saving, and antibiotics should be given as soon as possible. Intramuscular or intravenous penicillin can be given by GPs or paramedics. In hospital, intravenous cannulation will allow blood for blood culture, blood count and clotting studies to be drawn before the first antibiotic dose is given. Lumbar puncture – provided there is no contraindication – can be performed once treatment is underway. Do not wait to give antibiotics in a child who is obviously unwell.

Table 16.1 Organisms causing meningitis

Age	Pathogens	Treatment
Neonatal period (birth-28 days)	Streptococcus group B Escherichia coli Other coliforms Listeria monocytogenes	Amoxicillin and gentamicin or cefotaxime
28 days and older	Meningococcus Haemophilus influenzae Pneumococcus	Ceftriaxone
Any age	Viruses: enterovirus, mumps, influenza	Supportive
Any age	Tuberculosis	Seek specialist advice

Lumbar puncture will confirm the diagnosis of meningitis and help determine the cause (Table 16.2). Even if antibiotics prevent growth from CSF culture, polymerase chain reaction (PCR) will detect bacterial DNA in blood or CSF and enable a diagnosis.

Table 16.2 Cerebrospinal fluid findings in infection

Be sensitive when talking to the family: the word ‘meningitis’ is very powerful and surrounded by much myth in the media. It is important to be honest about the possible diagnosis whether it is a certainty or a suspicion. Most parents worry that an ill child has meningitis whether they say so or not – voice your thoughts and demonstrate that you are serious in investigating and treating this possibility.

Bacterial meningitis still has a mortality of around 5%; meningococcal septicaemia is even more dangerous, with reported mortality very high if the initial presentation is with shock. Of the survivors, 10% have sequelae – most commonly deafness, especially after pneumococcal meningitis. Hearing screening should be performed on all children after meningitis (see also Chapter 14, p. 206).

Do not forget that meningitis is an infectious and notifiable disease. Meningococcal infection, in particular, is recorded as occurring in household contacts of the index case. In the UK, cases should be reported to local public health authorities. Household and other close contacts should be treated with prophylactic antibiotics.

Encephalitis

Case 16.2

A boy with Herpes simplex encephalitis

James, a 4-year-old boy, presented with a 3-day history of fever and lethargy. He had been rather irritable, off his food, and had had some diarrhoea. He then had a flurry of brief tonic-clonic seizures and was admitted unconscious – responding only to painful stimuli. He had no neck stiffness, was not shocked but had a fever of 38.9°C. His mother was noted to have a large cold sore. He was promptly treated with high-dose intravenous antibiotics and aciclovir. An EEG showed diffuse slowing, compatible with encephalitis. PCR testing of CSF later confirmed herpes simplex virus infection.

Diagnosis of encephalitis is a clinical dilemma, as shown in Case 16.2. Why is the boy so drowsy? He could have post-ictal drowsiness following febrile seizures, but the history suggests encephalitis. Lumbar puncture will normally show a CSF lymphocytosis suggesting brain inflammation secondary to encephalitis, tuberculous meningitis, or partially treated bacterial meningitis where there is a history of antibiotic use. Send CSF and stool for virology and seek specialist microbiological advice. Diarrhoea may indicate an enterovirus infection. Most viral encephalitis is self-limiting, but herpes simplex encephalitis is often aggressive and damaging. Children with encephalitis are therefore treated with aciclovir until the diagnosis is clear. Children may also get encephalitis after viral infections as part of the immune response to the original infection. Measles, mumps, varicella and rubella can all do this.