Part 12
INFECTIONS IN CHILDHOOD
12.1
Infectious diseases of childhood
D. Isaacs
Infectious diseases of childhood are still a significant cause of illness in children, especially in the first years of life. Although immunization has resulted in a very marked reduction in many of the childhood infections that in previous times caused significant morbidity and mortality (Ch. 3.5), some of these infections are still seen and others have yet to have effective vaccines developed. This chapter describes the features of some of these infections.
Measles (rubeola, morbilli)
Measles virus is a paramyxovirus, one of the RNA viruses. It causes measles, one of the most important of the childhood exanthems, due to its high infectivity and virulence. At the end of the twentieth century measles still caused a million childhood deaths a year worldwide.
The rash of measles is mediated by T cells: infected subjects with defective T cells (cellular immunity) get little or no rash, but classically develop a giant cell pneumonia. Measles infection also causes significant suppression of host T cell immunity, resulting in anergy to tuberculin (negative Mantoux test) and increased susceptibility to diarrhoeal and respiratory illness.
Epidemiology
•Respiratory droplet spread, highly infectious, causing outbreaks every 2 years in unimmunized populations
•From 1978–1992 in Australia over 10 children a year died from measles, as a result of acute encephalitis or pneumonia
•As immunization levels improved, the number of deaths fell to 1–2 per year from 1992, and there have been none since 1995, when a second dose of measles vaccine was introduced at 4–5 years of age
•In developing countries, the high mortality is mainly due to pneumonia, often with bacterial (staphylococcal or pneumococcal) superinfection
•Children in developing countries who recover from measles have increased mortality for a year afterwards because of the resultant suppression of cellular immunity
•Measles is highly contagious and over 98% of adults in unimmunized communities are seropositive.
Clinical features (Figs 12.1.1, 12.1.2)
•Incubation period 10–14 days
•Prodromal period (symptoms before rash) 3–5 days, with high fever, irritability, cough, exudative conjunctivitis, otitis media, and white spots on buccal mucosa (Koplik spots)
•Rash starts behind ears and descends: blotchy, raised rash, confluent in places
•Child miserable and febrile when rash present
•Cervical lymphadenopathy, conjunctivitis, otitis media and wheeze commonly accompany rash.
Complications
See Table 12.1.1.
Differential diagnosis
•In roseola infantum (see below) the rash can be identical to measles but appears as the fever subsides, and the child looks well
•Other viruses causing morbilliform (measles-like) rash on occasions: enteroviruses, Epstein–Barr virus (EBV), influenza, parinfluenza
•Antibiotics, especially amoxicillin or ampicillin, may cause a rash
•Kawasaki disease
•Scarlet fever.
Laboratory diagnosis
•Rapid antigen detection: immunofluorescent antibody stain on nasopharyngeal secretions
•Serology: measles-specific IgM or fourfold or greater rise in IgG titre.
Treatment
•Mainly symptomatic in industrialized countries
•Vitamin A therapy recommended for severe cases and malnourished children
•Antibiotics for bacterial complications, particularly pneumonia.
Prevention
•Measles is a vaccine-preventable disease
•There are effective live, attenuated vaccines
•There is only one serotype of measles
•Humans are the only host
•It should be possible to eradicate measles from the world by immunization
•In developing countries, routine vitamin A supplementation reduces the mortality of measles. In Australia measles–mumps–rubella (MMR) vaccine is given at 1 year of age and a second dose at 4–5 years of age (note that maternal antibody is generally protective before 1 year and interferes with immunogenicity if vaccine is given earlier)
•Measles vaccine is contraindicated for immunosuppressed children. If exposed to measles, they should be given normal human immunoglobulin, as ‘passive’ protection.
Clinical example
Harriet, 3 years old, was in preschool with a friend who 2 weeks earlier (1) had a cough and fever (2) and later came out in a rash. Neither had been immunized against measles (3). Harriet developed a high fever, runny nose and cough (4) and was irritable. Her eyes became red and weepy (5) and her ears were sore (6). After 3 days (2) her doctor found bilateral otitis media (6) and white spots on a red background on her buccal mucosa (7). Next day she remained miserable and hot, and developed a rash behind her ears, which spread over the next 2 days to her face, trunk and limbs, and was pink to red and blotchy (8). In some areas the rash joined up and was raised. She had scattered wheezes bilaterally (4). She remained febrile and unwell for 3 days, then the rash faded, leaving a brown discoloration of the skin with desquamation of the fingers and toes (9).
The following are features typical of measles infection:
•Incubation period 10–14 days (1)
•Infectious during the prodromal period, which lasts 3–5 days (2)
•Immunization over 95% protective (3)
•Bronchitis (4), exudative conjunctivitis (5) and otitis media (6) almost invariable features
•Enanthem called Koplik spots (7)
•Rash is classically descending, blotchy to confluent, papular (8), with desquamation, often more marked in children from developing countries (9).
Roseola infantum (exanthem subitum)
•Caused by infection with human herpesvirus 6 (HHV-6) and occasionally HHV-7
•Affects infants aged 6–18 months
•Morbilliform (measles-like) rash appears as high fever subsides
•Child well and afebrile when rash appears (in contrast to measles)
•May get febrile convulsions in acute phase
Clinical example
Mark, a 9-month-old baby who was previously well, developed a runny nose, fever and irritability (1) and went off his feeds. After 2 days, he had a generalized, tonic–clonic seizure (2), which stopped after 2 minutes. He was admitted to hospital, where he was found to have a fever of 40°C, cervical lymphadenopathy (3) but no rash or enanthem (4). A lumbar puncture was normal. After 24 hours observation in hospital his fever subsided but he developed a diffuse papular rash on his trunk, thought at first to be measles (5). He was well and was discharged home. Serology for HHV-6 revealed positive specific IgM.
The following are features typical of roseola infantum. (1), (3) Usual presenting features, lasting 2–3 days. Febrile convulsion (2) is a recognized complication. No enanthem (4). Rash often misdiagnosed as measles but the child with roseola is well and the fever falls as the rash appears (5), in contrast to measles.
Rubella (German measles)
The main importance of rubella virus is its teratogenic effect on the fetus, causing congenital rubella syndrome.
Epidemiology
•Respiratory droplet spread
•Causes spring and summer epidemics in unimmunized communities
•Mainly affects children aged 5–10 years but also non-immune pregnant women
•Less infectious than measles: 15–20% of adults in unimmunized populations (including south-east Asia) are non-immune
•Most rubella infections are subclinical.
Clinical features (Figs 12.1.3, 12.1.4)
•Incubation period 14–21 days
•Rash much fainter and less florid than measles, not raised
•Rash often starts on face in young children, spreads to neck, trunk and extremities
•Lymphadenopathy usual, particularly suboccipital, postauricular and cervical
•Adolescents and adults often get more constitutional symptoms: conjunctivitis, arthralgia or arthritis, malaise, fever
•Encephalitis, purpura are rare complications
•Congenital rubella syndrome results from first-trimester rubella infection (Ch. 11.4).
Diagnosis
Non-immune pregnant woman exposed to possible rubella: send acute serum for rubella-specific IgM and IgG (usually measured by enzyme-linked immunosorbent assay (ELISA)) and a convalescent serum 2–4 weeks later, looking for rubella IgM and/or a rising IgG titre.
Clinical example
Rosie, 7 years old, was off colour for 2 days with headache and low grade fever to 38°C (1). Several of her school-friends had been unwell with fever and rash in the past few weeks, including her best friend 2 weeks ago (2). Rosie then developed a fine rash on her body, a sore throat and a cough, but no joint symptoms (3). Her neck was sore on the day the rash appeared and lymph nodes could be seen in her neck, behind her ear and at the back of her head. Her eyes were slightly red (3). The next day she felt better, and the day after was almost back to normal (4). A clinical diagnosis of rubella was made.
Her mother was 10 weeks pregnant and went to see the doctor (5). The doctor found she had been rubella-seronegative when she booked for her pregnancy with Rosie (her only child), but had not been immunized against rubella after delivery (6). The doctor took blood from Rosie’s mother for rubella IgM and IgG and made an appointment for 2 weeks for repeat serology (7).
(1) The prodromal period of rubella is short for children aged 5–9 years (the peak age), who may have no symptoms prior to the rash. Adolescents and adults, in contrast, may have a preceding 1–5 days of fever, headache, sore throat, cough, and often arthralgia or arthritis. The incubation period is 14–21 days (2). The rash and lymphadenopathy (3) are characteristic but not diagnostic and other infections such as erythema infectiosum (slapped cheek disease) can cause clinically similar outbreaks in schoolchildren. The symptoms improve rapidly (4). The major concern is close contact with women in the first trimester of pregnancy (5). In most countries, women are screened for rubella antibodies at booking (6). If they are seronegative, they should be immunized with rubella vaccine (usually in the form of MMR vaccine) after delivery (6). A non-immune pregnant woman in contact with a child with clinical rubella should have serology performed, because women may develop asymptomatic rubella (7). The serology should be repeated 2 weeks later, to look for seroconversion, i.e. the appearance of rubella IgM or a fourfold or greater rise in IgG (7).
Differential diagnosis
•Many other viruses cause rubelliform rashes
•Clinical diagnosis of rubella is notoriously unreliable
•Rubella is very rare in infancy: other viruses, e.g. enteroviruses, HHV-6 are much more likely to cause infantile rashes.
Prevention
•Live attenuated rubella vaccine is usually given universally as MMR in industrialized countries
•Congenital rubella syndrome is rare in industrialized countries such as Australia but common in developing countries.
Erythema infectiosum (slapped cheek disease, fifth disease)
•Caused by human parvovirus B19 (parvo small)
•Spread by respiratory route
•Causes epidemics in school aged children, which mimic rubella outbreaks
•Initial presentation is with fever, cervical lymphadenopathy and facial rash resembling sunburned cheeks (viraemic phase)
•Subsequently develop lacy, reticular rash on limbs and trunk, sometimes with arthralgia or arthritis (immune-complex-mediated) (Figs 12.1.5, 12.1.6)
•The virus infects red cell precursors in the bone marrow, causing no effect in normals (haemoglobin drops by 1g/dl) but severe anaemia in those with shortened red cell survival (e.g. children with abnormal haemoglobin or fetus)
•In sickle cell disease and other hereditary anaemias, infection causes aplastic crises due to red cell aplasia
•Infection during the second or third trimester of pregnancy can cause fetal hydrops due to fetal anaemia.
Varicella (chickenpox)
Chickenpox (Figs 12.1.7, 12.1.8) is a highly infectious disease causing a bullous (pox-like) rash. The DNA virus responsible, varicella-zoster virus (VZV), is a herpesvirus and has the ability to remain dormant in the dorsal root ganglia and reactivate as herpes zoster (shingles).
Epidemiology
•Occurs worldwide, although spreads less readily in tropical countries
•Highly infectious, spread by respiratory route, due to infectious particles from burst vesicles and from respiratory tract
•Incubation period 10–21 days, short prodromal period of 1–2 days
•Peak age incidence is 2–8 years.
Complications
•Bacterial superinfection of skin
•Pneumonia/pneumonitis:
•varicella pneumonitis occurs in immunocompromised children but also in pregnant women and normal adults
•bacterial pneumonia (pneumococcal or staphylococcal) can rarely complicate varicella pneumonitis
•Encephalitis:
•incidence about 1 in 1000 cases
•most common form is pure cerebellar ataxia, with complete recovery over days to weeks
•severe form is acute disseminated encephalomyelitis (ADEM), a postinfectious demyelinating illness with high morbidity and mortality
•Haemorrhagic chickenpox – severe illness in subjects with profound defect in cellular immunity (e.g. oncology patients), indicating importance of T cells in recovery from VZV infection
•Congenital varicella syndrome – affects up to 2% of babies whose mothers develop chickenpox in pregnancy.
Diagnosis
•Usually clinical
•Can grow virus from blister fluid in tissue culture or detect antigen by immunofluorescence on vesicle fluid
•Can use serology (IgG, IgM).
Prevention
•Live attenuated VZV vaccines are now available and are highly protective
•Varicella zoster immune globulin (ZIG or VZIG) is an immunoglobulin preparation with a high titre of anti-VZV IgG antibodies. It is used for passive prophylaxis of immunocompromised patients (e.g. oncology patients, neonates) exposed to VZV.
Treatment
The antiviral drug acyclovir inhibits viral thymidine kinase and can be used to treat children with severe varicella.
Clinical example
Charles, aged 6, had been in contact with a schoolfriend who was off school 2 weeks ago with chickenpox. Charles had a sore throat and fever of 38°C but no spots. Next day, a few small red spots like mosquito stings appeared on his trunk and limbs and on his scalp under the hair. These became raised, then developed into small, fluid-filled blisters surrounded by a small area of erythema. They were intensely itchy and when scratched readily became superinfected and left a scar. These spots crusted over within hours but fresh crops of vesicles kept appearing on Charles’s face, trunk and limbs. He had difficulty swallowing and his eyes were red and sore. He was miserable but not unwell and was troubled by the intense pruritus. After a week, the last spot had crusted and the scabs disappeared over the next 2 weeks.
The following are features typical of varicella. Incubation period 10–21 days. Short 1–2 day prodrome during which infectious (not infectious during the incubation period). Spots under hairline characteristic and distinguish from insect bites. Start as macules, then progress to papules, vesicles or pustules. If scratched they may become infected, the commonest complication, and leave a scar or pockmark. They come in crops, and can infect the pharynx, palate and conjunctivae of the lids. The child is infectious until the last spot crusts.
Zoster (herpes zoster, shingles)
•VZV can remain dormant in the dorsal root ganglia of sensory nerves after primary infection and reactivate many years later as zoster. Zoster follows a dermatome distribution and was the means by which the distribution of the sensory nerves was mapped. Vesicles form a band and do not usually cross the midline. They can occur on the trunk and limbs or follow cranial nerves. The Ramsay Hunt syndrome presents with vesicles on the pinna of one ear and facial nerve palsy due to zoster of the geniculate ganglion.
•Zoster infection in a previously well child is almost always benign and not suggestive of underlying malignancy.
•About 10% of children whose mothers developed chickenpox during pregnancy will develop zoster in early childhood: if a young child gets zoster, ask about chickenpox in pregnancy.
•Immunocompromised children are at increased risk of zoster.
•Neuralgia before, during and after zoster is very uncommon in children, in contrast to adults.
•Most childhood zoster does not need specific treatment but intravenous acyclovir is indicated for ophthalmic zoster (to prevent eye damage) or if the child is immunocompromised (to prevent life-threatening disseminated infection).
Mumps (epidemic parotitis)
•Infectious disease of childhood, 90% before adolescence
•Preventable by immunization with live attenuated virus (usually given as MMR vaccine)
•Causes swelling, pain and tenderness of the parotid glands
•Can rarely be unilateral but unilateral neck swelling more suggestive of alternative diagnoses (e.g. lymphadenopathy, autoimmune parotitis)
•Other salivary glands, sublingual and submandibular, may be involved
•Complications include viral meningitis (symptomatic in 10% of children with mumps, asymptomatic in over 50%), encephalitis, orchitis, oophoritis, pancreatitis, thyroiditis, deafness and rarely ophthalmitis, arthritis, myocarditis and nephritis.
Scarlet fever and scarlatina
•Scarlet fever (Figs 12.1.9, 12.1.10) is a toxin-mediated disease caused by exotoxins elaborated by group A streptococcus (Streptococcus pyogenes) and coded by plasmids
•These toxins act as ‘superantigens’, causing widespread T-cell activation because they can bind to the edge of the T-cell receptor and bypass its usual highly specific recognition of antigens
•Analogous superantigen-mediated diseases include toxic shock syndrome and Kawasaki disease.
Scarlatina is a mild form of scarlet fever, often affecting preschool age children, whereas scarlet fever is commonest at age 5–10 years.
In both, the primary site of group A streptococcal infection is the throat, causing exudative tonsillitis and/or pharyngitis.
In preantibiotic days, scarlet fever, and the related erysipelas, was a quarantinable disease, highly contagious and with a high mortality. Although scarlet fever became less common after the 1940s, it has re-emerged, perhaps due to the re-emergence of strains producing virulent exotoxins.
Diagnosis
Positive throat swab or positive serology: high or rising titre to streptolysin O (ASOT) or deoxyribonuclease B (anti-DNAase B).
Clinical example
Anna, 7 years old, presented with fever and sore throat for 2 days, followed by a rash. Her tonsils were red and covered in spots of white exudate. Her tongue had prominent red papillae. Her face looked red but was white around the mouth, like a clown. The rash was red, patchy and rough to the touch, and covered her whole body. In the axillae and groins there were lines of petechiae. Her cervical lymph nodes were enlarged and tender. She was treated with penicillin and rapidly improved. Two weeks later she had extensive peeling of her hands and feet.
The following are features typical of scarlet fever. Exudative tonsillitis; strawberry tongue; circumoral pallor; sandpaper rash; Pastia’s lines; tender cervical lymphadenitis; peripheral desquamation.