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.

Fever and a rash

This is a common presentation. It may help to sort these cases out using the following scheme:

1. Could the child be seriously ill? Many viral infections produce a non-specific rash and fever. It is often not possible to make an accurate diagnosis, in which case the trick is to sort out those who are worryingly ill from those who are not.

2. Has the child been given antibiotics? You could be observing a sensitivity reaction or a modified presentation of a bacterial infection.

3. What is the appearance and distribution of the rash?

Non-blanching rash

If the rash does not blanch on pressure, it could be meningococcal infection. A purpuric rash may also occur with Henoch–Schönlein purpura (see Chapter 6, p. 55), but the child does not appear markedly unwell, and the distribution of the rash over the buttocks, extensor forearms and lower limbs is characteristic (so-called ‘gravitational’ distribution of rash).

Meningococcal septicaemia

The cause of meningococcal infection – Neisseria meningitidis (meningococcus) – may present with meningitis, or, as is the case in Case 16.3, an overwhelming septicaemic illness. This occurs at any age and may progress with frightening speed.

Case 16.3

A baby with meningococcal septicaemia

Jasper, a 3-month-old baby, presented with a 6-hour history of being unsettled, off feeds and with a fever. On assessment he looked pale and unwell. The fontanelle was tense and he had persistent, high-pitched crying. His pulse was 160 beats per minute, capillary refill 5 seconds, and respiratory rate 40 breaths per minute. On examination he had a rapidly spreading purple rash that did not blanch on pressure, which is characteristic of meningococcal septicaemia.

He was immediately given a bolus of 20 mL/kg of normal saline, and high-dose intravenous antibiotics.

Antibiotic therapy is imperative, and shock and multiorgan failure are likely with such a presentation (for management, see Appendix I, p. 288). High dependency or intensive care is imperative. Lumbar puncture to confirm meningitis is deferred until the child is stable. The initial rash in meningococcal septicaemia may be a blanching, maculopapular rash, but it quickly changes character to become petechial or purpuric.

Generalized maculopapular rash

The principal differential diagnosis lies between measles, rubella, roseola infantum, slapped-cheek disease and drug/allergic reactions, particularly following aminopenicillin use in glandular fever (see below). Kawasaki’s disease (see below) is distinguished by the presence of other features.

Measles

Case 16.4

A boy with measles

Sammy, a 2-year-old, presented with a rash which followed 48 hours of fever and coryza. The rash started behind the ears and spread rapidly to involve the whole body. He had a widespread maculopapular rash and was miserable and very unwell with a high fever and conjunctivitis. He had not received any immunizations.

Measles is uncommon where immunization rates are high. A decline in measles immunization rates in the UK lead to the reappearance of this previously rare, but highly infectious disease (as in Case 16.4). As public confidence in the MMR immunization has increased, so immunization rates nationally have risen (in April 2011, the Department of Health reported that 88.9% of children under 2 years had received at least one MMR immunization) but they remain too low to prevent measles outbreaks, particularly in urban areas. At the time of writing, a large measles outbreak was underway in France, (under 2 year immunization rate 87.0%), with nearly 5000 cases reported in the first quarter of 2011.

Measles is always a nasty illness and may be complicated by pneumonia, encephalitis and otitis media, leaving a significant morbidity and mortality, especially in the very young, and in adults. Koplik spots, which can make the diagnosis (described as like grains of white salt on a red background inside the mouth), are seen only in the first couple of days – usually before the rash. The period of infectivity ranges from about 4 days before the onset of the rash, to about 4 days after its appearance.

Rubella

Rubella is a relatively trivial illness. The rash typically lasts about 3 days, and comprises fine 1–4 mm pink maculopapules (as in Case 16.5). Particularly in adolescents, it may be preceded by an upper respiratory tract prodrome – painful eye movements are characteristic. A troublesome post-viral arthropathy may follow. Rubella is important because it causes significant damage to the fetus if acquired by a pregnant mother. Rubella embryopathy comprises the triad of deafness, cataracts and retinopathy, and congenital heart disease, coupled with other features. It is entirely preventable. Women found not to be rubella-immune in pregnancy are offered immunization after pregnancy.

Case 16.5

A girl with rubella

Julie, a 5-year-old girl, was under the weather one day with a slight fever. She developed a fine pinkish maculopapular rash over her body. Examination revealed tender, enlarged, occipital lymph nodes.

Roseola infantum

Case 16.6

A toddler with roseola infantum

Ryan, a 1-year-old, presented with a febrile convulsion, associated with a 2-day history of very high fever (>40°C), and malaise. There were no specific findings on examination. He had a neutropenia on his blood count. He was treated with intravenous antibiotics, pending blood cultures, but as the fever subsided on day 3 a rose-pink maculopapular rash appeared.

Roseola infantum is a harmless infection caused by human herpes virus 6B (HHV6B). Febrile seizures occur with it quite commonly, as in Case 16.6. The characteristic feature is the appearance of the rash, concurrent with remission of fever. The rash is a diffuse maculopapular, rose-pink rash, readily distinguished from measles by the remission of fever. Neutropenia, as in Case 16.6, is characteristically found.

Slapped-cheek disease

Case 16.7 gives an example of a condition that is caused by parvovirus B19. Children with sickle-cell anaemia or other haemolytic anaemias may develop a severe aplastic crisis (see Chapter 7, p. 61). The fetus may develop hydrops fetalis if a mother catches this infection while pregnant.

Case 16.7

An outbreak of parvovirus

There was an outbreak of illness in a local primary school one December. Several children developed a bright red rash over their cheeks with pallor around the mouth. The fever and the facial rash settled in a few days, although some children had a more generalized rash which might have fluctuated for a week or more. A few children developed arthritis in the following days.

Urticaria

Some of the most dramatic rashes you will ever see are urticarial. Large red wheals usually with an irregular, raised edge are found on the trunk. The rash may come and go within a few hours, sometimes leaving a slightly bruised appearance. Symptomatic treatment with antihistamines and prednisolone is effective. (see Chapter 8, p. 83).

Generalized vesicular rash

Chicken pox

Case 16.8

A boy with chicken pox

Thomas, a 5-year-old boy, had come into contact with chicken pox in his cousin 3 weeks previously. After a short prodrome with fever he developed scattered discrete spots. These were initially red papules but rapidly developed into small vesicles. These spots were very itchy and healed within a few days by crusting over only to be replaced by a fresh crop.

Case 16.8 is an example of chicken pox (varicella) which is caused by varicella zoster, a herpes group virus. In most children the systemic upset and the rash are mild but a few children are covered with spots and are thoroughly miserable. Following exposure, viraemia develops about 6 days after infection, with fever. Subsequently, fever, malaise and abdominal pain develop, before the onset of the rash about 10–14 days after initial contact (though it may be as late as 21 days).

Secondary infection is the commonest complication. Around 5–10% of children get secondary bacterial infection – usually from scratching. A small number get super-infection with group A Streptococcus, which may produce toxic shock, necrotizing fasciitis, or septicaemia, with a very high mortality rate. Viral pneumonia, typically about 3–4 days after onset of rash, is a serious complication in the immunocompromised, in older children and adults, with progressive respiratory failure necessitating intensive care. Chest pain, wheezing and tachypnoea, with diffuse lung involvement on X-ray, are characteristic. Acute encephalitis, with depressed conscious level, affects 1.7/100 000 cases, and has a mortality rate of 5–10%. Post-infectious cerebellar ataxia, typically ocurring 2–4 weeks after initial infection, is much more commonly seen and is benign. Cerebral vasculitis resulting in stroke may occur months after initial infection.

Although chicken pox is relatively harmless in most children, it represents a major threat to those with reduced immunity. Children on steroids, those being treated for leukaemia and other malignancies, and the newborn, are at high risk and may develop lethal systemic or encephalitic infection. The parents and children in these cases should be warned of the risk and report any possible contact with chicken pox (or shingles). Oral or systemic aciclovir taken as soon as possible after exposure will attenuate disease severity. In very high-risk patients, zoster immune globulin may be required. Specialist advice is required in all cases. The herpes zoster virus may lie dormant for years but re-emerge as shingles. This acutely painful vesicular eruption along one dermatome is rare in childhood.

Rash restricted to one site

Impetigo, erysipelas and cellulitis are cutaneous infections caused by staphylococci or streptococci (see Chapter 8, p. 84). Impetigo and erysipelas usually affect the face. There are obvious local inflammatory changes, sometimes with regional lymphadenopathy. Cellulitis may overlie osteomyelitis (see Chapter 6, p. 51). Treatment is with oral or intravenous antibiotics. Red, painful raised lesions over the shins, erythema nodosum, may occur with drug reactions and a variety of infections or inflammatory disorders (see Chapter 8, p. 84).

Fever and rash associated with sore throat or oral lesions

Pharyngitis or tonsillitis with rash occurs in scarlet fever, glandular fever and Kawasaki’s disease. Cervical lymphadenopathy is often marked, especially in Kawasaki’s disease. Mumps is characteristically associated with parotid enlargement, which is often unilateral at first.

Sore throat

Glandular fever

Case 16.9

A teenager with glandular fever

Alan, a 15-year-old boy, presented with a 4-day history of fever and a terrible sore throat. On examination he had enlarged tonsils covered with a white exudate and petechiae on his palate. His breathing was partially obstructed and sounded noisy. He had enlarged tonsils and cervical and axillary lymphadenopathy. His spleen tip was palpable. He had a fine maculopapular rash. Alan was advised to avoid contact sports until the splenomegaly had resolved, due to increased risk of splenic rupture.

Case 16.9 is an example of glandular fever, a condition that has an ominous reputation among adolescents for causing prolonged illness. This reputation is offset to some extent by the kudos of catching a disease thought to be spread by kissing! The incubation period is about 6 weeks. Glandular fever can be very unpleasant in the acute stage but most children make a prompt recovery. Typical symptoms include sore throat, flu-like symptoms, malaise, swelling around the eyes (20%) and a diffuse maculopapular rash (10%). Subclinical hepatitis is usual, with derangement of liver function tests, but overt jaundice is uncommon. The causative agent – Epstein–Barr virus – may be detected on paired antibody titres. Cytomegalovirus and toxoplasmosis may cause a similar illness. A glandular fever-like illness accompanies seroconversion in some HIV-infected patients. The monospot and Paul Bunnell screening tests are useful for Epstein–Barr virus, but false positives and false negatives occur. Ampicillin or amoxicillin must be avoided in the empirical treatment of sore throat – as a florid maculopapular rash occurs, typically 10–14 days later – and may be complicated by Stevens–Johnson syndrome (Chapter 8, p. 84). Treatment is usually supportive. Steroids may be used to reduce airway obstruction or swallowing difficulty secondary to severe tonsillar enlargement.

Scarlet fever

Case 16.10

A girl with scarlet fever

Gemma, aged 6 years, became febrile with a sore throat. After 48 hours a bright red rash appeared initially in the axillae and groins, and spread rapidly. Her face was red but the area around the mouth remained pale (circumoral pallor). The tongue was white and furred (strawberry tongue). As the rash faded the surface layer of skin peeled away – desquamation.

The girl in Case 16.10 has scarlet fever. The primary cause is usually a toxin-producing beta-haemolytic group A Streptococcus, although staphylococcal scarlet fever may also occur. The toxin produces generalized erythema. Treatment is with a 10-day course of penicillin or a macrolide antibiotic such as azithromycin. Late complications include pneumonia, rheumatic fever (see Chapter 6, p. 57) and acute nephritis (see Chapter 11, p. 129). Kawasaki’s disease may present similarly (see below).

Kawasaki’s disease

Kawasaki’s disease is a vasculitic disorder of unknown aetiology. The key feature is an unremitting high fever lasting for 5 days or more in a child who is irritable and unwell. It is rare but is serious and treatable. The principal differential diagnosis is scarlet fever (see above) (see Figure 16.1).

Figure 16.1 Features of Kawasaki’s disease.

The rash can take many forms but typically it is a maculopapular rash that begins in the groin or perineum. Other features include conjunctivitis, a sore mouth (stomatitis) with strawberry tongue and lymph node enlargement. There may be swelling of the hands and feet and later in the illness the peripheral skin may peel, particularly around the nails. A chronic symmetrical arthritis affecting knees, hips and ankles may occur.

About 5% of children, especially young boys, develop coronary artery aneurysms. Follow-up echocardiography is necessary to monitor for this complication. Sudden cardiac death (see also Chapter 9, p. 98) is a rare complication of coronary artery aneurysms, or other cardiac complications.

Treatment with high-dose aspirin and immunoglobulins produces symptomatic relief and reduces the risk of coronary aneurysms. Recent evidence suggests that the addition of pulsed methylprednisolone may improve outcome.

Fever and rash associated with mouth ulcers and lesions on the lips

Herpes simplex

Herpes simplex virus may cause cold sores in older children and adults. These are acutely painful red swollen lesions of the lips with a pus-filled centre. Younger children who acquire herpes for the first time may get herpetic gingivostomatitis. This produces an acutely painful ulcerated mouth, tongue and lips. Children may be unable to swallow and need intravenous fluids. Oral aciclovir treatment speeds recovery. Mouth ulcers also occur with enteroviral infections, particularly coxsackie virus (see also Chapter 8, p. 85).

Fever and rash affecting the palms or soles

The commonest infectious cause is hand, foot and mouth disease, caused by coxsackie viruses, which also produces vesicles on the skin and mouth ulcers. Erythema multiforme with its characteristic target lesions may also affect the hands and feet. Mucosal involvement may signify Stevens–Johnson syndrome (see Chapter 8, p. 84).

Fever and specific symptoms

Specific symptoms accompany many infections:

• Dyspnoea and respiratory distress in pneumonia and bronchiolitis

• Intractable cough in pertussis

• Diarrhoea and vomiting in gastroenteritis

• Loin pain or dysuria in urinary tract infection

• Limp and pain in septic arthritis or osteomyelitis

• Jaundice in hepatitis

• Ear ache in middle-ear infection.

These conditions are discussed in the relevant chapters.

Parotid swelling

Parotitis may occur with mumps (see below), HIV, parainfluenza and enteroviruses, or bacterial infections, and may be recurrent or chronic. Parotid swelling causes the pinna to be angled outwards, which is readily visualized from behind.

Mumps

Mumps is uncommon in the UK, thanks to immunization. The parotid swelling is usually unilateral at onset, but in 70–80% of cases both glands are affected. A truncal maculopapular rash occurs infrequently. Meningo-encephalitis occurs in 10%, but is usually benign. Deafness – usually unilateral – may ensue. Orchitis affects 35–40% of adolescents and adult males.

Fever of unknown origin

A persistent, unexplained high fever (fever of unknown origin, FUO) is rare and is a difficult diagnostic challenge. A logical approach is helpful, with severe symptoms prompting more invasive investigations. Clinical evaluation must be regularly repeated to detect new signs, such as heart murmurs.

Infection must be sought assiduously with repeated blood, urine and stool cultures. Viral studies should include glandular fever organisms. A chest X-ray, abdominal and pelvic ultrasound, and bone scan may be indicated if the fever is persistent and associated with significant symptoms. A tuberculin skin test may indicate underlying tuberculosis. Bone marrow aspirate for culture and to exclude leukaemia should be considered in protracted FUO. Neuroblastoma or lymphoma may also underlie FUO.

Inflammatory disorders such as Kawasaki’s disease, systemic onset juvenile idiopathic arthritis (Still’s disease), inflammatory bowel disease and polyarteritis nodosa may be responsible.

A history of foreign travel or insect bites should prompt appropriate investigations for malaria, Lyme disease, leptospirosis and rickettsial diseases.

Malaria

Worldwide, malaria is a very common cause of high fever and is seen from time to time in the UK. Think of it in children who have travelled recently to malarial zones. Thick and thin blood films will confirm the diagnosis, and indicate the parasite count. The most serious malarial infection is due to Plasmodium falciparum, which accounts for nearly all malarial deaths.

Classic symptoms are swinging fever, headaches, chills, rigors and night-sweats. Cerebral malaria results from occlusion of the cerebral microvasculature by infected red cells. Severe haemolysis may complicate P. falciparum infection, potentially leading to blackwater fever with acute renal failure. Artenusate is now recommended as optimum treatment for acute malaria. Quinine is no longer advised.

Lyme disease

Lyme disease is uncommon in the UK – there are about 2000 cases each year in the UK. It is caused by the spirochaete Borrelia burgdorferi, transmitted by the bite of the deer tick. A red macule or papule forms and progressively enlarges up to 30 cm in diameter, with partial central clearing. This rash – erythema chronicum migrans – is pathognomonic. This initial infection is followed months later by a mono- or pauciarticular arthritis of the knees and other large joints. Uncommonly, neurological and cardiac complications occur. Diagnosis is made on serological testing. Treatment is with tetracyclines or penicillins.

Immune deficiency

The immune system comprises physical barriers to infection – skin and epithelial surfaces, and humoral and cell-mediated immunity. In practice, impaired immunity is most commonly seen with steroid therapy (supraphysiological) or other immunosuppressant or cytotoxic drugs. It is imperative that these patients and their physicians are aware of the risk and have a management plan for possible infection. In particular, they must be warned of the risk posed by chicken pox and measles infection.

Patients without a functioning spleen (e.g. following splenectomy, or in sickle-cell anaemia, where progressive splenic infarction occurs) are at increased risk of infection with polysaccharide encapsulated organisms – notably pneumococcus, Haemophilus influenzae B and meningococcus. Prophylactic penicillin V and targeted immunization based on antibody levels is recommended post-splenectomy.

Diseases causing immunodeficiency – congenital or acquired – most often present with frequent and/or unusually severe infections, failure-to-thrive and chronic diarrhoea. In older children, malignant disease, particularly non-Hodgkin’s lymphoma, may supervene.

See Box 16.2 for investigation of suspected immunodeficiency.

Box 16.2

Investigation of suspected immunodeficiency

• Full blood count and blood film

• Lymphocyte subsets

• HIV test

• Immunoglobulins (including IgE) and IgG subclasses

• Specific antibodies to tetanus, Haemophilus influenzae, Pneumococcus (if immunized)

• Complement CH50, C2–C6 levels

• Alpha-fetoprotein, calcium, skin-prick tests

Disorders impairing antibody-producing B-lymphocytes or granulocytes result in impaired bacterial killing with recurrent upper and lower respiratory tract, skin and bone infections. Complete antibody deficiency is usually an X-linked disorder – Bruton’s agammaglobulinaemia. The commonest disorder of bacterial killing, chronic granulomatous disease, is additionally complicated by development of multiple granulomas leading to lymphadenopathy and hepatosplenomegaly. Partial antibody deficiencies are less severe. In common variable immunodeficiency, there is deficiency of IgG, and to a lesser extent IgA and IgM. IgG₂, IgG₄ and IgA deficiencies predispose to chest infections, particularly with Pneumococcus. Secondary antibody deficiency occurs in nephrotic syndrome.

Antibody deficiency may be treated with regular infusions of immunoglobulin.

Some immune deficiency disorders are associated with elevated immunoglobulins – notably Job’s syndrome (elevated IgE with red hair, severe eczema and frequent bacterial skin and sinopulmonary infections).

Complement deficiencies are rare, but lead to increased bacterial infections, especially with Meningococcus if the terminal complement pathway is affected (C5–C9).

Defective cell-mediated immunity is seen with Di George syndrome (see Chapter 18, p. 272) due to thymic hypoplasia, but normally a degree of recovery takes place. Thymus transplantation may be performed if necessary. More severe disorders of cell-mediated immunity include severe combined immunodeficiency (SCID) and HIV/AIDS.

SCID presents with severe and protracted infections with failure-to-thrive. Treatment is with bone marrow transplantation, although experimental gene therapy has been used for one variety – adenosine deaminase deficiency.

See Box 16.3 for the management of immune deficiency.