Although many bacteria are still susceptible to long-established treatments, antibiotic resistance is an increasing problem worldwide. Examples of particular clinical concern include:

• Penicillin (and cephalosporin)-resistant Streptococcus pneumoniae (PRP).
  
• Methicillin (multidrug)-resistant Staphylococcus aureus (MRSA).
  
• Community-acquired non-multiresistant MRSA (CA-MRSA).
  
• Glycopeptide (vancomycin and teicoplanin) intermediate-resistant Staphylococcus aureus (GISA).
  
• Vancomycin-resistant Enterococcus (VRE).
  
• Multidrug-resistant Mycobacterium tuberculosis (MDRTB) and extensively drug-resistant tuberculosis (XDRTB).
  
• Bacteria that produce inducible b-lactamases (IBL) which are always present in bacteria of the ‘ESCHAPPM’ group comprising Enterobacter spp., Serratia marscesens, Citrobacter freundii, Hafnia spp., Aeromonas spp., Providencia spp., Proteus vulgaris and Morganella morganii.
  
• Bacteria that produce extended-spectrum â-lactamases (ESBL), e.g. some E. coli and Klebsiella spp. which are associated with cephalosporin (and often gentamicin resistance).
  
• Multidrug-resistant Salmonella spp.
  
• Macrolide-resistant Streptococcus pyogenes.

Infections with resistant organisms should be considered in patients who have had prolonged hospitalisation, known exposure to resistant organisms or failed response to initial empiric therapy. Strategies to deal with infections caused by these organisms include using new or broader-spectrum antibiotics, or alternatively using two or more antibiotics concurrently. The choice of empiric therapy becomes increasingly difficult. Specialist consultation is strongly advised.

Fever is the most common presenting symptom in children in the primary care setting. Although there is no universally accepted definition, fever is generally considered to be present if core temperature (rectal or tympanic) is >38 °C. Axillary and oral temperatures may underestimate body temperature by at least 0.5 °C.

Although tympanic thermometers provide certain advantages over other thermometers (ease of use, rapid results and convenience), several studies have found that they are not as accurate nor sensitive for the detection of fever, particularly in infants <3 months of age. Rectal (neonates), oral and axillary (neutropenic patients) temperatures are preferable for accurate fever detection.

Self-limiting viral infections are the most common cause of fever in children. However, the challenge to the clinician is to identify those children with a more serious cause. Fever in children may be classified into three groups:

• Fever with localising signs.
  
• Fever without focus.
  
• Fever (or pyrexia) of unknown origin.

Fever with localising signs

A careful history and examination will identify the source of infection in most patients. These children should be managed according to the individual condition and its severity.

Fever without focus

In a small number of children presenting with fever, no focus is found. Most will have a viral infection, but a more serious illness such as a urinary tract infection (5–8%), occult bacteraemia (<1%) or meningitis may be present. Infants (<12 months old) with rectal temperature >38.0 °C have a higher risk of occult bacteraemia (up to 15%).

Most children who present with fever and no identifiable focus appear otherwise well. History should include details about immunisation status, infectious contacts, travel, diet and contact with animals. A thorough physical examination should be carried out, paying particular attention to:

• General appearance: the level of activity and social interaction; peripheral perfusion and colour.
  
• Vital signs: pulse; respiration; blood pressure.
  
• Possible clues to source: full fontanelle, neck stiffness, photophobia; respiratory distress (tachypnoea; grunt; nasal flare; retractions), abnormal chest signs; rhinitis, pharyngitis, otitis or mastoiditis; lymphadenopathy; abdominal distension, tenderness or masses; hepatosplenomegaly; bone and joint tenderness or swelling; skin rashes, petechiae or purpura, or skin infection.
  
• Always consider Kawasaki disease in any child with a persistent fever. It is the only rare cause of persistent fever that requires urgent treatment.

Patients with unexplained fever with a higher likelihood for serious infection include the following patient groups or conditions:

• Neonates and infants <3 months of age.
  
• Immunocompromised (e.g. congenital immunodeficiency, HIV, neutropenic and other oncology patients, cytotoxic drugs and steroids).
  
• Asplenic children (congenital, post splenectomy or functional, e.g. sickle cell disease).
  
• Patients who have received prior oral antibiotics. Many of these patients have a viral infection, but meningitis or other serious bacterial infection must be considered.
  
• Children with central venous or arterial catheters, or other foreign bodies, including shunts.
  
• Multiple congenital abnormalities.
  
• Other specific illnesses (e.g. sickle cell disease, cystic fibrosis or structural cardiac defects (endocarditis)).
  
• Toxic-appearing children (e.g. those with an altered conscious state, decreased peripheral perfusion (check capillary refill centrally) or purpuric rash).
  
• Children <6 months of age (higher chance of UTI).
  
• Children <12 months of age with febrile convulsion, or any children with febrile convulsion lasting longer than 10 min (consider lumbar puncture to exclude meningitis).

These children require admission to hospital, with culture of blood, urine and CSF (‘full septic screen’) and a chest radiograph if indicated. Antimicrobial therapy should be based on the patient’s clinical illness and the local epidemiology of potential pathogens and their antibiotic susceptibility (see Antimicrobial guidelines).

Group A streptococcus

Group A â-haemolytic streptococci (GABHS or Streptococcus pyogenes) cause a variety of diseases including pharyngotonsillitis (see chapter 24, Ear, nose and throat conditions), impetigo, cellulitis, scarlet fever, otitis media, streptococcal toxic shock syndrome, necrotising fasciitis, glomerulonephritis and rheumatic fever. Group A streptococcal pharyngitis is extremely uncommon in children <5 years of age. S. pyogenes is currently always sensitive to penicillin.

Scarlet fever

• Transmission: droplet, direct contact.
  
• Incubation period: 2–5 days.
  
• Infectious period: 10–21 days (24–48 h, if adequate treatment).

Clinical features

• Prodrome: sudden-onset high fever, vomiting, malaise, headache and abdominal pain.
  
• Rash: appears within 2 h of prodrome, diffuse red flush involving torso and skin folds, blanches, circumoral pallor, strawberry tongue (initially white, then red day 4–5), pharyngotonsillitis, tender cervical/submaxillary nodes.

Complications: otitis media, retropharyngeal abscess, quinsy, rheumatic fever, glomerulonephritis.

Diagnosis: culture of throat swab may confirm clinical impression

Treatment:

• phenoxymethylpenicillin (penicillin V) 250 mg p.o. (<10 years), 500 mg p.o. (>10 years) 12 hourly for 10 days.
  
• Control of case: exclude from school until treated for 24 h.
  
• Differential diagnosis: Kawasaki disease, streptococcal or staphylococcal toxic shock syndrome, viral infection

Acute rheumatic fever

• Incubation period: 7–28 days after group A streptococcal infection.

Clinical features

Jones criteria (1992) for initial diagnosis: two major, or one major plus two minor manifestations, plus evidence of antecedent group A streptococcal infection by culture or serology.

• Major manifestations:
  

  – Carditis (usually mitral regurgitation murmur).

  
  

  – Polyarthritis.

  
  

  – Erythema marginatum.

  
  

  – Subcutaneous nodules.

  
  

  – Chorea (does not require evidence of recent GAS infection).

  
  
• Minor manifestations:
  

  – Fever.

  
  

  – Polyarthralgia or aseptic mono-arthritis.

  
  

  – Raised inflammatory markers (ESR ≥30 mm/h or CRP ≥30 mg/L).

  
  

  – Prolonged PR interval on ECG.

Recurrences may be diagnosed with three minor manifestations plus evidence of antecedent group A streptococcal infection without major manifestations, if there are no other more likely diagnoses.

Complications

Increased risk of recurrent disease, particularly for first 5 years after an attack. Heart valve damage may be permanent, especially after severe or recurrent disease, leading to rheumatic heart disease.

Diagnosis

Clinical features (Jones criteria) + culture/serology. Echocardiography may be useful in detecting subclinical lesions or typical rheumatic valvular involvement.

Treatment

• Admission to hospital.
  
• Phenoxymethylpenicillin (penicillin V): 250 mg p.o. (<10 years), 500 mg p.o. (>10 years) 12 hourly for 10 days or a single i.m. injection of benzathine penicillin G (900 mg, or 450 mg if <30 kg).
  
• Aspirin:
  

  – Weeks 1 and 2: 25 mg/kg p.o. 6 hourly (4–8 g/day total in adults) initially. – Weeks 3 and 4: Reduce to 15 mg/kg p.o. 6 hourly.

  
  

  – May be used to relieve arthritis or fever and leads to resolution of symptoms within 1–2 days (sometimes this response is diagnostic of rheumatic fever).

  
  

  – There is no evidence that aspirin affects the long-term outcome.

  
  
• Corticosteroids (usually prednisolone 2 mg/kg per day, tapering after 2 weeks) are often used when carditis with cardiac failure is present, although there is no definitive evidence that they improve long-term outcome.
  
• For severe chorea, haloperidol, sodium valproate or other major tranquillisers have been used with mixed success.

Follow-up

Secondary prophylaxis is essential to prevent subsequent group A streptococcal infections, which may cause recurrences. Phenoxymethylpenicillin (penicillin V) 250 mg p.o. twice daily, or benzathine penicillin G 900 mg i.m. every 3 or 4 weeks. Duration is until 21 years of age or 5 years after last attack (whichever is later) or to age 35 years if moderate or severe carditis present. Prophylaxis may be lifelong if severe carditis or if patient has required cardiac surgery. Long-term clinical and echocardiographic follow-up is essential.

Post-infectious glomerulonephritis

See chapter 35, Renal conditions.

Streptococcus pneumoniae

Streptococcus pneumoniae (pneumococcus) is a Gram-positive coccus (usually appearing as diplococci) that causes a wide variety of infections including severe, invasive disease (e.g. meningitis, septicaemia, septic arthritis, peritonitis), or mild, often self-limited, invasive disease (occult bacteraemia), pneumonia, otitis media and sinusitis.

Transmission

Droplet.

Epidemiology

The epidemiology of pneumococcal disease in children is changing as a result of the routine use of conjugate pneumococcal vaccine. In trials, the vaccine provided ∼70% protection against invasive disease (meningitis, septicaemia), ∼50% protection against radiographically proven pneumonia, and <5% protection against otitis media caused by Pneumococcus. Routine use of this vaccine in the USA has led to a large decrease in invasive pneumococcal disease in children, particularly in disease caused by penicillin-resistant strains. The incidence of pneumococcal disease is likely to fall in Australia but there remains concern about the possibility of a rise in disease caused by non-vaccine serotypes (‘serotype replacement’). Despite the decreasing incidence of pneumococcal disease, this bacterium remains the most common cause of pneumonia, otitis media and meningitis in children.

Most human disease caused by 23 serotypes (of the 90 serotypes that have been described). 7 serotypes (those in the conjugate vaccine) cause about 85% of invasive disease in non-Aboriginal Australian children. Incidence of invasive disease is about 50–100 cases per 100 000 children aged <5 years. Incidence in central Australian Aboriginal children is the highest in the world (∼1000–2000 per 100,000 aged <5 years, before the introduction of pneumococcal vaccine). Antibiotic resistance is becoming a problem worldwide – organisms are classified as penicillin susceptible, penicillin-non-susceptible (PNSP), and cefotaxime/ ceftriaxone susceptible or resistant. Resistance may be intermediate or high-level.

Clinical features

Pneumonia and otitis media are the most common presentations, followed by septicaemia and meningitis. Soft tissue, bone and joint infections are less common manifestations.

Diagnosis

Meningitis, septicaemia or other sterile site infection is confirmed by culture/Gram stain of appropriate specimen (blood, CSF, joint fluid, peritoneal fluid, etc.). Pneumococcal pneumonia is blood culture positive in only about 10–20% of cases. PCR-based testing of blood and CSF is available and useful when antibiotics have been initiated before collection of specimens. Pneumococcal urinary antigen has poor specificity in children due to frequent pharyngeal carriage of pneumococcus.

Treatment

Penicillin or amoxicillin is the drug of choice, except in CNS infection with PNSP.

• If non-CNS infection with PNSP, treat with high-dose penicillin (benzylpenicillin 60 mg/kg (max. 2 g) i.v. 4 hourly for invasive disease including pneumonia, or amoxicillin 90– 120 mg/kg per day p.o. divided into three or four doses for otitis media or sinusitis).
  
• If CNS infection with cefotaxime/ceftriaxone-non-susceptible pneumococci, use vancomycin plus rifampicin or, for PNSP with cefotaxime MIC ≤ 2.0 mcg/mL, use high-dose cefotaxime (300 mg/kg per day) as an alternative (see Bacterial meningitis, p. 407). Duration of treatment is 10 days for meningitis and usually 5–7 days for other infections.

Vaccines

The 7-valent conjugate pneumococcal vaccine (7PCV, Prevenar®) has been part of the routine immunisation schedule in Australia since 2005 (2001 for indigenous children). 7PCV is given at 2, 4 and 6 months of age. A fourth dose in the second year of life is recommended for children at high risk of invasive pneumococcal disease, including those with hyposplenism. 9- and 13-valent conjugate vaccines are likely to be available in the near future.

The 23-valent polysaccharide vaccine provides protection against a broader range of serotypes but is not immunogenic in children <18–24 months of age, and protection is not long-lasting (2–3 years). The vaccine is routinely recommended in risk groups such as indigenous Australians, those with respiratory or cardiac co-morbidities, and patients with hyposplenia or certain immuno deficiencies.

Neisseria meningitidis

Neisseria meningitidis (meningococcus) is a Gram-negative diplococcus that mainly causes meningitis or septicaemia, or both. Less commonly, it may cause other infections including conjunctivitis, septic arthritis, pharyngitis, pneumonia, occult bacteraemia. For recommendations specific to meningitis see Bacterial meningitis, p. 407.

• Transmission: droplet.
  
• Incubation period: usually hours to 3 days.
  
• Infectious period: as long as carried – may be months. Most virulent within days of acquisition.

Epidemiology

• Peak age groups <2 years and 15–24 years.
  
• Serogroups B and C are most common in Australia (A, Y and W135 usually confined to travellers).
  
• Traditionally, group B is most common in young children and group C more common in adolescents.
  
• Incidence of group C meningococcal infection, which had been steadily rising in Victoria until 2003, has fallen rapidly since the introduction of routine conjugate group C vaccine.
  
• The case fatality rate has been reported as 5% for group B and 14% for group C infection.

Clinical features

• Meningitis – see below, p. 407.
  
• Septicaemia: often non-specific prodrome suggestive of viral illness.
  
• Rapid progression with any or all of the following: fever, rash (classically purpuric or petechial, but can be less specific), malaise, myalgia, arthralgia, vomiting, headache, reduced conscious state.
  
• Chronic meningococcaemia occurs rarely (consider terminal complement deficiency), and may be associated with progressive purpuric rash.

Diagnosis

Initially based on clinical features. Confirmation by culture of blood and/or CSF, preferably collected before first dose of antibiotics, although treatment should not be delayed. Additional tests may include shave biopsy of skin lesions (for Gram stain and culture), PCR on blood, CSF or skin sample.

Treatment

• Shock must be managed appropriately (see chapter 1, Medical emergencies).
  
• Discuss with Intensive Care for all cases of meningococcaemia and those with meningitis <2 years or very unwell.
  
• Immediate i.v. antibiotics (cefotaxime 50 mg/kg per dose (max. 2 g) 6 hourly, or if unavailable, benzylpenicillin 60 mg/kg per dose (max. 2 g) 4 hourly).
  
• Duration of antibiotics usually 7 days. Can change to i.v. benzylpenicillin when isolate identified as meningococcus. All cases should be notified immediately to statutory health authorities.
  
• Steroids
  

  – Meningococcaemia: Consider corticosteroids (hydrocortisone 1 mg/kg i.v. 6 hourly) in severe cases.

  
  

  – Meningitis: (Children > 4 weeks old) give dexamethasone 0.15 mg/kg i.v. 6 hourly.

  
  
• Immunoglobulin 0.5 g/kg i.v. over 4 hours, is considered in those requiring ICU.

Clearance antibiotics for contacts

Cytomegalovirus

Cytomegalovirus (CMV) is a ubiquitous herpes virus. It persists in latent form after primary infection and reactivation can occur years later, particularly with immunosuppression.

Transmission

• Horizontal: salivary contamination or sexual transmission; blood transfusion/organ transplantation.
  
• Vertical: transplacental, intrapartum via passage through infected genital tract and postnatal via ingestion of CMV-positive breast milk.

Incubation period

Unknown; infection usually manifests 3 weeks to 3 months after blood transfusion and 4 weeks to 4 months after tissue transplantation.

Clinical features

Vary with age and immunocompetence of child; asymptomatic infection is most common. Cytomegalovirus mononucleosis: cervical lymphadenopathy; hepatosplenomegaly in children, fever in adults. Note, clinical signs of CMV infection are similar to graft rejection in transplant patients. Both events peak 30–90 days after transplantation.

Diagnosis

Identification of the virus by culture or PCR of urine or saliva in the first 3 weeks of life is diagnostic of congenital disease; after this period, positive results may represent postnatally acquired infection. PCR of stored dried blood spots taken for the neonatal screening test may aid the diagnosis.

Distinguishing past from active infection can be difficult. Viral culture (rapid enhanced tissue culture immunofluorescence) or PCR of urine, saliva and even blood may be misleading as CMV can be excreted intermittently for life after primary infection, especially in immunocompromised patients. Leucocyte antigenaemia assay (degree of antigenaemia) correlates with the severity of CMV disease and is therefore a good means of predicting disease and monitoring progression in immunocompromised patients.

Complications

• Encephalitis, myocarditis, pneumonia, haemolytic anaemia, thrombocytopenia are rare manifestations.
  
• Primary CMV infection has been described in conjunction with Guillain–Barré syndrome and other peripheral neuropathies.
  
• Pneumonia, retinitis, hepatitis and colitis in immunocompromised.
  
• Congenital infection: >90% appear normal at birth: CNS sequelae in 10–20% of these (mainly sensorineural hearing loss); 5% present early with petechiae, hepatosplenomegaly, microcephaly and thrombocytopenia and have high rates of neurological sequelae.

Treatment

• Ganciclovir or valacyclovir for active CMV disease in the immunocompromised. Cytomegalovirus hyperimmune globulin is also sometimes used in these patients.
  
• Ganciclovir therapy should be considered in any neonate with symptomatic congenital CMV to reduce the risk of hearing loss and other neurological sequelae.

Enterovirus (non-polio)

Coxsackie A, B and echoviruses are important causes of childhood infections, especially in the summer months. These include a wide range of clinical presentations, including nonspecific febrile illness; pharyngitis; herpangina; hand, foot and mouth disease; gastroenteritis; aseptic meningitis; encephalitis; myocarditis; pericarditis and several forms of viral exanthem (maculopapular, vesicular, petechial). Infection in agammaglobulinaemic patients can cause particularly severe or persistent meningoencephalitis. In neonates, enteroviral infection may be difficult to distinguish clinically from bacterial sepsis.

Hand, foot and mouth disease

• Cause: coxsackie A virus (usually A16).
  
• Transmission: direct contact/droplet.
  
• Incubation period: 3–6 days.
  
• Infectious period: until blisters have gone.

Clinical features

Vesicles on cheeks, gums, sides of the tongue; papulovesicular lesions of palms, fingers, toes, soles, buttocks, genitals, limbs (may look haemorrhagic); sore throat; fever and anorexia.

Diagnosis

Tests are usually unnecessary as the clinical picture is sufficient for diagnosis.

Control of case

Exclusion is unnecessary (as virus is excreted in faeces for weeks).

Treatment

Symptomatic.

Epstein–Barr virus (infectious mononucleosis)

• Incubation period: 30–50 days.
  
• Infectious period: unknown, viral excretion from oropharynx for months.

Clinical features

Glandular fever: Fever, malaise, exudative tonsillopharyngitis, generalised lymphadenopathy and hepatosplenomegaly. Highly variable clinical course: acute phase lasts 2–4 weeks and convalescence may take weeks to months. May be associated with hepatitis or CNS involvement. In immunocompromised (particularly transplant patients), can cause severe lymphoproliferative disease.

Diagnosis

Atypical lymphocytes in the peripheral blood. Monospot test in blood for heterophile antibody identifies 90% of cases in older children and adults, but lacks sensitivity in children under 4–5 years of age. Serology is the gold standard. PCR of blood or tissue may be helpful in transplant patients.

Complications

Upper airway obstruction; dehydration from poor oral intake (uncommon). An unknown minority may develop symptoms of chronic fatigue syndrome. See also chapter 15, Adolescent health.

Treatment

Symptomatic: prednisolone 1 mg/kg (max. 50 mg) oral, daily may be considered in patients hospitalised for airway obstruction. Amoxicillin and ampicillin cause florid rash in up to 90% of children with EBV infection.

In patients with splenomegaly, avoidance of contact sports is recommended for 3–4 weeks after the onset of the illness to prevent splenic rupture.

Herpes simplex virus (HSV)

Manifestations of HSV infection include skin and mucous membrane involvement, gingivostomatitis (mainly HSV-1), genital herpes (mainly HSV-2), eczema herpeticum (see chapter 23, Dermatologic conditions), herpetic whitlow and eye involvement. HSV encephalitis is an important treatable condition that must not be missed (see p. 413 and chapter 33, Neurologic conditions, p. 461). Pneumonia and disseminated infection occur in the immunocompromised. Congenital infection also occurs. Infection can be primary (e.g. gingivostomatitis) or from a reactivation of the latent virus (e.g.cold sores).

Primary herpes gingivostomatitis

• Transmission: droplet, direct contact.
  
• Incubation period: 2–14 days
  
• Infectious period: indeterminate; virus can be excreted for at least 1 week, occasionally months. Shed intermittently with or without symptoms (including cold sores) for years afterwards.

Clinical features

Fever, irritability, cervical lymphadenopathy, halitosis, diffuse erythema and ulceration within the oral cavity (buccal mucosa, palate, gingiva and tongue) and mucocutaneous junction. Duration 7–14 days.

Diagnosis

Immunofluorescence or culture of vesicular scrapings.

Complications

Poor oral intake; autoinoculation resulting in herpetic whitlow, keratitis or genital herpes; eczema herpeticum; dissemination (particularly in immunocompromised).

Treatment

Symptomatic: topical anaesthesia (e.g. 1–2% lignocaine [lidocaine] gel, xylocaine viscous), analgesia (paracetamol), fluids and a soft diet. Aciclovir, valaciclovir or famciclovir should be considered if immunocompromised.

HSV in pregnancy

Primary infection during the first 20 weeks of gestation is associated with an increased risk of spontaneous abortion, stillbirth and congenital disease. Beyond 20 weeks, premature labour and growth retardation are more common. Primary infection after 34 weeks is associated with high rates of neonatal disease.

Neonatal HSV

Transmission

• Intrapartum (70–85%): perinatal acquisition from maternal genital tract; usually presents day 5–19.
  
• Postnatal (10%): usually presents day 5–19.
  
• Intrauterine (5%): transplacental; usually presents within 48 h of birth.

to infants with neonatal HSV infection give no history of genital HSV in themselves or their partners. The risk of infection to a baby of an asymptomatic woman with a history of recurrent genital herpes is <3%.

Clinical features

Neonatal infection presents in three ways:

• Localised skin, eye and/or mouth (‘SEM’) disease (45%). Onset 7–14 days. Death is rare; 30% or more of patients eventually develop evidence of neurological impairment.
  
• CNS disease (50%). Onset 14–21 days, in the form of encephalitis or a more disseminated disease. Mortality is 15%; 50–60% of survivors have psychomotor retardation, with or without microcephaly, spasticity, blindness, etc.
  
• Disseminated disease (20%). Onset 5–10 days. Involves any organ but primarily liver and adrenals; encephalitis occurs in 70% or more of patients. Presentation includes irritability, seizures, respiratory distress, jaundice, coagulopathy, shock and characteristic vesicular rash. Note: About 20% of babies never have skin lesions. Mortality is 50–60% (in spite of treatment) and neurological sequelae in 40%.

Diagnosis

Viral isolation from neonatal vesicular fluid, mouth or conjunctival swabs, stool, urine, leucocytes and maternal genital tract swabs. HSV antigens are detected by immunofluorescence. Serology is not always helpful, as maternally acquired IgG confounds interpretation in the neonate and IgM may not be produced until 2 weeks after the onset of illness. Detection of viral DNA by PCR (especially in CSF to detect subclinical CNS disease) is helpful. Changes on EEG, CT and MRI may all provide supporting evidence of HSV infection.

Complications

Overall mortality (following treatment) is 15–20% and 40–50% of infants have some neurological impairment.

Treatment

Aciclovir 20 mg/kg i.v. 8 hourly (see Antimicrobial guidelines, Appendix 3) for at least 14 days (SEM disease) or 21 days (CNS or disseminated disease). Suppressive treatment with aciclovir, for 6–12 months, should be considered for CNS or disseminated disease.

Prevention

20% of newborns born to women with primary HSV will be infected, even if delivered by Caesarean section.

HSV encephalitis

See Encephalitis, p. 413 and chapter 33, Neurologic conditions, p. 461.

Human herpes virus 6 (roseola infantum)

95% of children are infected with human herpes virus 6 (HHV-6) by the age of 2 years. Up to 30% will present with the clinical features of roseola. HHV-7 has also been shown to be the cause in a small number of children. HHV-6 infection may also present as an acute febrile illness without a rash.

• Transmission: direct contact/droplet (asymptomatically shed).
  
• Incubation period: 9–10 days.
  
• Infectious period: unknown (greatest during period of the rash).

Clinical features

Roseola: fever with occipital lymphadenopathy; then rapid defervescence corresponding with appearance of a red, maculopapular rash over trunk and arms lasting 1–2 days.

Note: Many children are started on antibiotics for the fever and then misdiagnosed as having a drug reaction when the rash appears.

Diagnosis

Investigations do not usually alter management, but serology and PCR are available.

Complications

Febrile convulsions (HHV-6 is thought to be the cause of up to 1/3 of febrile convulsions in children <2 years of age), aseptic meningitis, encephalitis (rare), hepatitis.

Treatment

Symptomatic.

Influenza virus

• Cause: influenza A or B virus.
  
• Transmission: direct contact/droplet.
  
• Incubation period: 1–4 days
  
• Infectious period: 3–7 days after onset of symptoms. Longer in immunocompromised.

Epidemiology

Continuous genetic re-assortment of influenza A viruses can lead to epidemics; the degree of cross-immunity from previously circulating strains and vaccines determines whether this occurs. Large-scale epidemics (pandemics) occur when there is no protection from previous exposure. Although the virus may cause disease at any time, seasonal epidemics occur during the winter months.

Clinical features

Variable. Severity of illness is dependent on partial immunity from previous exposure to related influenza viruses and vaccines. Asymptomatic infection occurs. Commonly presents with fever and rigors; respiratory symptoms including coryza, pharyngitis, cough, pneumonia, wheeze or croup; headache, myalgias, fatigue. Vomiting and diarrhoea are less common.

Complications

Important complications include bacterial superinfection with pneumonia (especially S. aureus), otitis media or sinusitis; neurological: encephalitis, meningitis, encephalopathy; myositis and cardiomyopathy. Death occurs in ∼1% of hospitalised children.

Diagnosis

• Rapid diagnosis by immunofluorescence or PCR on respiratory specimens (nasal swab or NPA) may lead to early treatment.
  
• Viral culture is also important for epidemiology.

Control of case

Exclude from school until resolution of symptoms.

Treatment

• Neuraminidase inhibitors (zanamavir, oseltamivir) reduce the severity and length of illness by up to 36 h if started within 48 h, but earlier initiation is associated with the best outcome. Routine treatment of influenza in immunocompetent patients is not recommended.
  
• Neuraminidase inhibitors (oseltamivir ≥1 year of age, zanamavir ≥7 years of age) should be considered in children with laboratory-confirmed influenza, who are immunocompromised or who have chronic medical conditions.

Prevention

Vaccines can be used to prevent influenza in children.

• Trivalent inactivated intramuscular vaccine is ∼65% protective against influenza and prevents ∼30% of influenza-like illnesses, but efficacy varies from year to year. Annual vaccination with vaccine containing the most recent strains is necessary to provide continued protection. Two doses at least one month apart are recommended for children <9 years who are receiving influenza vaccine for the first time.
  
• Live attenuated vaccine is more effective (∼79% protective) but is not yet available in Australia.

Neuraminidase inhibitors may be used to prevent influenza in children at risk of complications.

Measles virus (rubeola)

As a result of widespread measles immunisation, this disease is now seen infrequently. However, outbreaks continue to occur in most parts of the world.

• Transmission: droplet, direct contact.
  
• Incubation period: 7–18 days (usually 14 days) to the appearance of a rash.
  
• Infectious period: 1–2 days before the onset of symptoms to 4 days after the onset of the rash.

Clinical features

• Prodrome: fever, conjunctivitis, coryza, cough and Koplik spots (white spots on a bright red buccal mucosa).
  
• Rash: appears 3–4 days later; erythematous and blotchy; starts at hairline and moves down the body, then becomes confluent; lasts 4–7 days; may desquamate in the second week.

Diagnosis

Serology (IgM is usually detectable 1–2 days after onset of rash, and almost always 4 days after), immunofluorescence and culture or PCR on nasopharyngeal aspirate.

Complications

Otitis media (1/4), pneumonia (1/25), encephalitis (1/2000), subacute sclerosing panencephalitis (SSPE) (1/25 000).

Treatment

Symptomatic: vitamin A should be considered for young infants with severe measles, the immunocompromised and those with vitamin A deficiency.

Control of case

Exclude from school for at least 5 days from the appearance of the rash.

Contacts

• Measles, mumps, rubella (MMR) vaccine should be given within 72 h of exposure, to unimmunised children >9 months of age (another dose should be given at 12 months of age or 4 weeks after the first dose, whichever is the later).
  
• If MMR is contraindicated, or if >72 h since exposure, normal human immunoglobulin should be given i.m. within 7 days (see chapter 29, Haematologic conditions and oncology).
  
• Exclude from school for 2 weeks if unimmunised.

Parvovirus B19 (erythema infectiosum, slapped cheek disease, fifth disease)

• Transmission: droplet, direct contact.
  
• Incubation period: 4–21 days.
  
• Infectious period: highly infectious until rash appears (50% of adults are immune).

Clinical features

Fever in 15–30%; non-specific prodrome. The rash has three stages:

• Slapped cheek appearance (1–3 days).
  
• Maculopapular rash: on proximal extensor surfaces, flexor surfaces and trunk; fades over next few days, then central clearing, forming a reticular pattern (after 7 days).
  
• Reticular rash: reappears with heat, cold and friction (weeks/months).

Diagnosis

Mainly clinical. PCR on blood and serology.

Arthritis; aplastic crisis in children with chronic haemolytic anaemia; bone marrow suppression; fetal hydrops.

Treatment

Symptomatic.

Control of case

School exclusion is inappropriate as the patient is no longer infectious once the rash appears.

Contacts

Pregnant contacts should seek advice regarding the unlikely possibility of intrauterine infection as treatment of fetal infection may prevent sequelae.

Rubella virus

• Transmission: droplet, direct contact.
  
• Incubation period: 14–21 days.
  
• Infectious period: 5 days before to 7 days after rash.

Clinical features

• 25–50% have no symptoms.
  
• Rash: small, fine, discrete pink maculopapules; starts on face and spreads to chest and upper arms, abdomen and thighs, all within 24 h.
  
• Prodrome: (1–5 days) low-grade fever, malaise, headache, coryza, conjunctivitis (more common in adults), postauricular/occipital/posterior triangle lymphadenopathy precedes rash by 5–10 days.

Diagnosis

Serology.

Complications

Congenital rubella syndrome: >25% affected if mother infected during 1st trimester; 10–20% have single congenital defect if infection occurs at 16–40 days.

Control of case

Exclude from school for at least 5 days from the onset of the rash.

Contacts

Check serology if pregnant. Immunoglobulin given after exposure in early pregnancy may not prevent infection or viraemia, but may modify risk of abnormalities in the baby.

Varicella zoster virus (chickenpox, shingles)

• Incubation period: 10–21 days. Shorter incubation in the immunocompromised. Zoster immune globulin (ZIG) may prolong incubation to 28 days.
  
• Infectious period: 1–2 days before appearance of the rash until the rash is fully crusted.

Clinical features

Fever, irritability, anorexia and lymphadenopathy. A pruritic rash develops over the next 3–5 days, which progresses from maculopapular to vesicular, followed by crusting by 5–10 days. Lesions appear in crops with a central distribution. Affects scalp, face, trunk, mouth, conjunctivae and extremities.

Diagnosis

Clinical diagnosis is usually sufficient. Immunofluorescence and culture or PCR of vesicular scrapings, or serology.

Complications

Secondary bacterial infection of skin lesions (most commonly group A streptococcus or S. aureus) or bacterial pneumonia; neurological (cerebellitis, transverse myelitis, Guillain–Barré syndrome); dissemination (pneumonitis, hepatitis, encephalitis) in patients with abnormal T-cell immunity. Herpes zoster (‘shingles’), resulting from a reactivation of the latent virus, is more common in children who have had chickenpox in infancy or who have been exposed in utero.

Treatment

• Aciclovir, famciclovir or valaciclovir in patients with impaired T-cell immunity. Antiviral treatment is not indicated in the immunocompetent child.
  
• Antibiotics for secondary bacterial skin infection (e.g. flucloxacillin).
  
• Aspirin is contraindicated because of the association with Reye’s syndrome.
  
• Other NSAIDs (including ibuprofen) should be avoided because of possible increased risk of invasive group A streptococcal disease.
  
• Paracetamol can be used.

Prevention

ZIG within 96 h of exposure (6 mL for adults, 4 mL for children 6–12 years of age, 2 mL for children up to 5 years of age). Indicated in the following patients in contact with varicella (or direct contact with shingles):

• Immunocompromised children (e.g. HIV, immunosuppressive therapy (including high-dose steroids; prednisolone 2 mg/kg or more per day) and patients with transplants, lymphoma, leukaemia or severe combined immune deficiency).
  
• Newborn infants whose mothers have varicella onset from within 7 days before delivery to 2 days after delivery.
  
• Infants under 28 days of age with non-immune mothers exposed to varicella.
  
• Hospitalised premature infants with no maternal history of varicella.
  
• Hospitalised premature infants <28 weeks gestation or <1000 g, regardless of maternal history.

Varicella vaccine

See chapter 9, Immunisation.

See also chapter 27, Gastrointestinal conditions.

Infectious diarrhoea continues to cause significant morbidity in children from developed and developing countries. In Australia, approximately 20 000 children (15/1000) <5 years of age are admitted to hospital each year with acute gastroenteritis. Rotavirus is the causal agent in up to 2/3 of hospitalised children where a pathogen is identified. Other important pathogens in hospitalised children include caliciviruses, enteric adenoviruses, astroviruses, Salmonella spp., Campylobacter jejuni, Giardia intestinalis (lamblia), Cryptosporidium parvum, enteropathogenic (and other) Escherichia coli, Shigella spp. and Yersinia enterocolitica.

• Children <5 years of age with rotavirus-positive gastroenteritis are unlikely to have another pathogen isolated from their faeces.
  
• It is unusual to find a protozoal parasite in the setting of acute diarrhoea.
  
• Repeat stool investigations are not helpful except in patients with chronic diarrhoea, suspected Salmonella carriage or parasitic infection.
  
• The cause of infectious diarrhoea can often be identified by simple laboratory studies but rarely alters management.
  
• Most bacterial causes of diarrhoea are self-limiting and do not usually require antibiotic therapy, even if blood or mucus is present. As with viral gastroenteritis, the primary aim of treatment is to achieve and maintain adequate hydration. Antibiotics should be considered for the immunocompromised and neonates.
  
• Nosocomial infection is common. Hence, adequate infection control measures established by the hospital are essential in preventing spread.

Rotavirus

• Incubation period: illness usually begins 12 h–4 days after exposure.
  
• Infectious period: most children shed the virus in the stools for up to 10 days; however, about 1/3 with severe primary rotavirus infection continue shedding for >21 days.

Clinical features

Major cause of severe diarrhoea in children causing over 50% of hospitalisations for acute gastroenteritis in children <5 years. Also a common cause of nosocomial infection. Annual peak period of infection occurs in the winter–spring period. Presents with diarrhoea, vomiting (may precede diarrhoea) and fever lasting for up to 1 week. Respiratory symptoms are common. May be complicated by dehydration, electrolyte imbalance and acidosis.

• Diagnosis: enzyme immunoassay and latex agglutination assay.
  
• Treatment: supportive, with particular attention to hydration.
  
• Vaccine: two safe and efficacious rotavirus vaccines are available. There is reasonable evidence that intussusception is not associated with these new vaccines (a concern with previous vaccines).

Adenovirus

Similar presentation to rotavirus, but there is no seasonality. It is more common under 12 months of age. Diarrhoea and vomiting may last longer and high fever is less common.

Salmonella (non typhi)

Clinical features

Broad spectrum of clinical syndromes including asymptomatic carriage, gastroenteritis, bacteraemia and focal infections (e.g. bone and joint). Age-specific attack rates are highest in children <5 years of age (peak at <1 year of age) and the elderly. Invasive infections and mortality are more common in infants, the elderly and those with underlying diseases.

Diagnosis

Does not usually alter management, but serology and PCR are available.

Treatment

Antibiotic treatment is not usually indicated for uncomplicated gastroenteritis as it may prolong excretion. Antibiotic treatment is indicated for bacteraemia, systemic involvement or infection in infants <3 months of age, those with underlying disease (e.g. immunocompromised) and elderly people. The choice and duration of treatment depends on the clinical manifestation and antibiotic susceptibility.

Campylobacter jejuni

More common >5 years of age. Causes diarrhoea with visible or occult blood, abdominal pain, malaise and fever. Antibiotic treatment is not usually necessary, except in special circumstances where the elimination of the carrier state is important, such as infection in food handlers.

Giardia intestinalis (lamblia)

Transmission

The most common parasite identified in stool specimens from children. More common in children (and staff) in childcare centres and returned travellers. The major reservoir and means of spread is contaminated water and, to a lesser extent, food. Person-to-person spread also occurs.

Clinical features

There is a broad spectrum of clinical manifestations, but the most common are: diarrhoea (usually persistent), abdominal distension, flatulence, abdominal cramps and weight loss/ failure to thrive.

Diagnosis

Confirmed by microscopy of stool specimens. These do not usually contain blood, mucus or leucocytes. Repeat specimens may be necessary.

Metronidazole 30 mg/kg (max. 2 g) p.o. daily for 3 days or tinidazole 50 mg/kg (max. 2 g) p.o. as a single dose are effective treatments for symptomatic giardiasis.

Dientamoeba fragilis

Transmission

This parasite is thought to be transmitted with the eggs of Enterobius vermicularis (pinworm).

Clinical features

Symptoms include acute or chronic diarrhoea and abdominal pain, although many infected children are asymptomatic. May be associated with eosinophilia.

Treatment

May be treated with metronidazole (dose as above) although treatment is unnecessary in asymptomatic patients where the organism is found incidentally.

Escherichia coli

There are at least five categories of diarrhoea-producing E. coli:

• Enterohaemorrhagic E. coli (EHEC): haemolytic uraemic syndrome (HUS), haemorrhagic colitis.
  
• Enteropathogenic E. coli (EPEC): watery diarrhoea in children <2 years of age in developing countries.
  
• Enterotoxigenic E. coli (ETEC): the major cause of traveller’s diarrhoea (usually self-limiting).
  
• Enteroinvasive E. coli (EIEC): usually watery diarrhoea, but may cause dysentery.
  
• Enteroaggregative E. coli (EAEC): chronic diarrhoea in infants and young children.

Antibiotic treatment is not usually indicated for diarrhoea caused by E. coli and may be associated with increased rates of HUS in EHEC infection.

Clostridium difficile

Transmission

Acquired from the environment or by faecal–oral transmission from a colonised host. Up to 50% of healthy neonates and infants <2 years of age are colonised, in contrast to 5% of those >2 years of age.

Clinical features

Rare cause of diarrhoea in those <12 months of age. Only clinically significant diarrhoea or colitis should be considered to be caused by Clostridium difficile. Pseudomembranous colitis usually occurs in patients on antibiotics (particularly penicillins, clindamycin and cephalosporins).

Treatment

• Cessation of antibiotics, and
  
• Oral metronidazole 7.5 mg/kg (max. 400 mg) p.o. 8 hourly for 10 days, and
  
• Consider probiotics – Saccharomyces spp. (baker’s or brewer’s yeast) or Lactobacillus spp.

Failure of treatment or recurrence may be due to reinfection, non-compliance, continued antibiotic use, or, rarely, a metronidazole-resistant organism. Options in this context include repeat metronidazole, oral vancomycin (not i.v.) or probiotics.

The most common worm infection in Australia. The highest rates of infection occurs in school age children, followed by preschoolers. In some groups, nearly 50% of children are infected.

Transmission

Eggs survive up to 2 weeks on clothing, bedding or other objects. Eggs often remain under the fingernails. Reinfection by autoinfection is common. Infection often occurs in more than one family member.

Incubation period

At least 1–2 months from the ingestion of eggs until the adult female migrates to the perianal region to deposit eggs.

Infectious period

Eggs are infective within a few hours of being deposited on the perianal skin.

Clinical features

Causes pruritus ani and vulvae.

Diagnosis

Visualisation of worms in the perianal region (at night) or microscopy of eggs collected on sticky tape briefly applied to perianal skin in the morning.

Treatment

Mebendazole 50 mg (<10 kg), 100 mg (>10 kg) p.o. (not in pregnancy or in those <6 months of age) or pyrantel 10 mg/kg (max. 750 mg) p.o. as a single dose, followed by a second dose 2 weeks later. All family members should be treated.

See also chapter 27, Gastrointestinal conditions.

Hepatitis A

Hepatitis A virus (HAV) is the most common viral hepatitis; it is particularly prevalent in developing countries.

• Transmission: faecal–oral route.
  
• Incubation period: usually about 4 weeks (2–7 weeks).
  
• Infectious period: viral shedding lasts 1–3 weeks; the highest titres in stool occur 1–2 weeks before the onset of illness, corresponding to the highest risk of transmission; lowest risk after onset of jaundice.

Clinical features

Usually an acute self-limited illness; mild, non-specific symptoms without jaundice in infants and preschoolers; fever, malaise, jaundice, anorexia and nausea in older children and adults.

Complications

Relapse (unusual), fulminant hepatitis (rare).

Diagnosis

Serology for HAV-specific IgM and IgG.

Treatment

Supportive.

Control of case

Children should be excluded from childcare or school for 7 days from the onset of illness, although the virus is excreted for many weeks.

Prevention

Inactivated HAV vaccine is recommended for travellers to endemic areas and patients with chronic liver disease (e.g. hepatitis B or C infection) or transfusion dependent illness.

Hepatitis B

Hepatitis B virus (HBV) infection is endemic worldwide. The prevalence of HBV and carriage rates vary in different parts of the world. The carriage rate is about 0.2% in Australians of European origin, and >10% in some indigenous populations. Rates are highest in those born in Asian or Mediterranean countries.

Transmission

Blood or body fluids that are HBsAg positive; vertical transmission occurs in infants born to HBsAg-positive mothers; there is a high risk of horizontal transmission in the first 5 years of life.

• Incubation period: 7 weeks–6 months.
  
• Infectious period: from several weeks before the onset until documented clearance of virus.

Clinical features

Symptomatic acute hepatitis (jaundice, anorexia, malaise and nausea) in adults; usually asymptomatic in young children, particularly in those <1 year of age.

Complications

The carrier state is associated with 25% mortality from hepatocellular carcinoma or chronic liver disease; lifelong follow-up is indicated. Those infected as infants or young children are more likely to become carriers and develop fatal complications as adults: 70–90% of infants infected at birth become chronic HBV carriers (particularly if the mother is HBeAg positive), in contrast to only 5% of adults. The remainder eliminate the virus and have no long-term effects.

Diagnosis

Test for:

• HBsAg (active disease).
  
• HBsAb (protection by vaccine or natural infection).
  
• HBeAg or HBV PCR (increased infectivity and risk of sequelae).
  
• HBcAb (past or present HBV infection).

Treatment

No specific therapy for HBV is available; á-interferon and nucleoside analogues may resolve chronic infection but are less effective if infection is acquired during childhood. Hepatitis A vaccination is recommended.

Prevention

• In Australia, recombinant HBV vaccine is currently recommended for all infants from birth, pre-adolescents, as well as those at high risk. Infants born to HBsAg-positive mothers should be given HBV-specific immunoglobulin plus a full course of HBV vaccination. They should be tested at 12–18 months with HBsAg and HBsAb.
  
• See needle-stick injuries (p. 419) for management of exposure to infected blood or body fluid.

Hepatitis C

Hepatitis C virus (HCV) causes acute and chronic hepatitis. The carriage rate is about 0.3% in apparently healthy new blood donors in Australia, but this probably underestimates the prevalence in the population, which may be around 1%.

Transmission

Parenteral exposure to HCV-infected blood and blood products; vertical transmission occurs from about 6% of HCV-positive mothers (higher if the mother is co-infected with HIV). Avoid use of fetal scalp electrodes; breast-feeding is not contraindicated but temporary avoidance is recommended if bleeding or cracked nipples; sexual transmission is rare.

• Incubation period: 6–7 weeks (range 2 weeks–6 months).
  
• Clinical features: mild, insidious hepatitis; usually asymptomatic in children.
  
• Complications: persistent infection in >85% (most children with chronic infection are asymptomatic); 65–70% develop chronic hepatitis, 20% develop cirrhosis. Uncommonly, hepatocellular carcinoma can develop in the absence of chronic hepatitis.
  
• Diagnosis: current or past infection is detected by serology (anti-HCV antibodies); current infection is confirmed by PCR for HCV RNA.
  
• Treatment:
  

  – Patients must be screened for chronic hepatitis, cirrhosis and hepatocellular carcinoma.

  
  

  – Optimal treatment regimens are under investigation. Hepatitis A and B vaccination is recommended.

Hepatitis E

Hepatitis E virus (HEV) is an uncommon cause of hepatitis, which occurs predominantly in tropical countries, especially in parts of India. Cases have been reported in travellers returning from these regions.

• Transmission: faecal–oral route, by contamination of water.
  
• Incubation period: 2–10 weeks.
  
• Infectious period: excreted in stool for 2 weeks after the onset of symptoms.
  
• Clinical features:
  

  – Similar to HAV infection. Most infected children have asymptomatic infection or mild gastrointestinal symptoms.

  
  

  – Mortality is rare, except in pregnant women.

  
  
• Diagnosis:
  

  – HEV-specific IgM.

  
  

  – PCR of stool and serum.

  
  
• Prevention: food and water safety in endemic countries.

Bacterial meningitis is a medical emergency.

Clinical features

• In infants, non-specific e.g. fever, lethargy, irritability or vomiting.
  
• In older children, headache, vomiting, drowsiness, photophobia and neck stiffness may be present. Kernig sign (inability to extend the knee when the leg is flexed at the hip) and Brudzinski sign (bending the head forward produces flexion of the legs) may be positive.

Diagnosis

Diagnosis is confirmed by examination of the cerebrospinal fluid (CSF), unless lumbar puncture (LP) is contraindicated (see chapter 3, Procedures). If LP is deferred or reveals no organism, identification of the pathogen may still be possible through:

• Blood cultures – often positive.
  
• PCR on blood or CSF for enterovirus, HSV and other viruses, TB, N. meningitidis and S. pneumoniae.
  
• Blood smear for Gram stain.
  
• Skin scraping or aspirate of purpuric lesions for N. meningitidis on Gram stain, PCR or (less likely) culture.
  
• Throat swab.

Antibiotics must be given immediately after the collection of appropriate cultures, but should not be delayed if the LP is to be deferred. Antibiotics should be rationalised to more specific treatment based only on final CSF or blood culture results.

Interpretation of cerebrospinal fliuid findings

Viral meningitis

The most common causes of viral meningitis or meningoencephalitis are enteroviruses (Coxsackie and echoviruses) and HHV-6 (see p. 396). Most cases are self-limiting; however, their clinical presentation can mimic bacterial meningitis. Enterovirus may be isolated from throat swabs and stools, and PCR of the CSF may be positive. Treatment is symptomatic except in the rare instance of infection in the immunocompromised where i.v. immunoglobulin (IVIG) may be used. Positive enteroviral PCR on CSF in a child with a consistent clinical presentation can allow for early cessation of antibiotics and discharge from hospital.

Tuberculous meningitis

Tuberculous meningitis is uncommon in Australia. It often presents in an insidious manner and can be difficult to recognise. Large volumes of CSF are required (at least 10 mL) for diagnosis by microscopy and culture of mycobacteria, or mycobacterial PCR (which is not necessarily more sensitive). Treatment with combination antitubercular antibiotics plus corticosteroids should be started early and requires specialist advice.

Encephalitis

Kawasaki disease (KD) is a systemic vasculitis that predominantly affects children under 5 years of age. Although the specific causal agent remains unknown, it is believed that KD is initiated by an infectious agent, although it is not transmitted from person to person. Early recognition and treatment are essential to reduce the risk of life-threatening complications.

Diagnosis

Diagnosis is often delayed because the features are similar to those of many viral exanthems. The diagnostic criteria for KD are:

• Fever for 5 days or more; plus
  
• Four of the following five features:
  

  – Polymorphous rash.

  
  

  – Bilateral (non-purulent) conjunctivitis.

  
  

  – Mucous membrane changes; e.g. reddened or dry cracked lips, strawberry tongue, or a diffuse redness of oral or pharyngeal mucosa.

  
  

  – Peripheral changes; e.g. erythema of the palms or soles, oedema of the hands or feet and desquamation in convalescence, particularly involving skin of hands, feet or perineal region.

  
  

  – Cervical lymphadenopathy (>15 mm in diameter, usually unilateral, single, non-purulent and painful).

  
  
• Exclusion of diseases with a similar presentation: staphylococcal infection (e.g. scalded skin syndrome and toxic shock syndrome), streptococcal infection (e.g. scarlet fever and toxic shock-like syndrome, but not just isolation from throat), measles, adenovirus and other viral exanthems, leptospirosis, rickettsial disease, Stevens–Johnson syndrome, drug reaction and juvenile chronic arthritis.

Particular clinical vigilance is needed to recognise patients with ‘incomplete’ or ‘atypical’ KD. Such patients do not fulfill the formal diagnostic criteria, but are still at risk of developing coronary artery aneurysms. Other relatively common features include arthritis, diarrhoea and vomiting, coryza and cough, and hydropic gallbladder.

Investigations

Laboratory features may include neutrophilia, raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), mild normochromic, normocytic anaemia, raised transaminases, hypoalbuminaemia and marked thrombocytosis in the second week.

Complications

Up to 30% of untreated children develop coronary artery dilation or aneurysm formation. This can occur up to 6–8 weeks after the onset of the illness. Echocardiography should therefore be done at least twice: at presentation and, if negative, again at 6–8 weeks to exclude coronary artery involvement. Coronary artery aneurysms can be associated with severe early ischaemic heart disease.

Management

Management includes early (preferably within the first 10 days of the illness) administration of IVIG (single dose of 2 g/kg i.v. over 10 h) and aspirin (3–5 mg/kg p.o. once a day (anti-platelet dose) for at least 6–8 weeks; maximum dose 150 mg). There is no evidence that using high (anti-inflammatory) dose aspirin decreases the risk of aneurysm development over and above that prevented by IVIG. However, some guidelines suggest using high dose aspirin (10 mg/kg p.o. 8 hourly) until defervescence. Paracetamol can be used for symptomatic relief.

A repeat dose of IVIG (2 g/kg) should be given to patients who fail to defervesce within 24 h after the completion of the first dose. Refractory cases with continuing fever and other signs of inflammation subsequent to this need specialist advice for further treatment that may include high-dose steroids (e.g. methylprednisolone 30 mg/kg i.v.).

Treatment with IVIG is highly effective in preventing the potentially devastating complication of coronary artery involvement. Treatment should still be undertaken in patients presenting after 10 days of illness if they have evidence of ongoing inflammation (fever, raised acute phase markers).

This is usually caused by an infection or inflammation of the lymph nodes. Malignancy is much less common.

Infectious causes

Acute bilateral lymphadenitis

• Viral upper respiratory tract infections.
  
• Systemic viral infections (e.g. EBV and CMV: may have generalised lymphadenopathy and hepatosplenomegaly).
  
• Kawasaki disease: may present initially as cervical lymphadenitis alone (see p. 414 above).

Acute unilateral lymphadenitis

• Group A streptococcus or Staphylococcus aureus: 40–80% of acute unilateral lymphadenitis; occurs at 1–4 years of age; fever, tenderness, overlying erythema; may be associated with cellulitis.
  
• Anaerobic bacteria: older children with dental caries or periodontal disease.
  
• Group B streptococcus may have overlying cellulitis (neonates).

Subacute/chronic unilateral lymphadenitis

• Bartonella henselae (cat-scratch disease): occurs about 2 weeks after a scratch or lick from a kitten or dog, usually involves axillary nodes, tender nodes; there may be a papule at infection site.
  
• Mycobacterium avium complex (MAC – formerly known as MAIS): patient usually 1–4 years of age, afebrile, systemically well and not immunocompromised; node usually unilateral, slightly fluctuant, non-tender, sometimes tethered to underlying structures and with violaceous hue to overlying skin.
  
• Toxoplasma gondii: systemic features (fatigue, myalgia), there may be generalised lymphadenopathy.
  
• Mycobacterium tuberculosis: usually a contact history; affects older children; systemic symptoms (e.g. fever, malaise, weight loss), non-tender nodes.
  
• HIV.

Management

Acute bilateral lymphadenitis without other signs (e.g. pallor, bruising or hepatosplenomegaly) is usually of viral cause and needs no specific treatment or investigation. Acute unilateral lymphadenitis with a fluctuant node needs incision and drainage (contra-indicated in suspected TB as may result in sinus formation). Otherwise, acute unilateral lymphadenitis is treated with oral flucloxacillin 25 mg/kg (max. 500 mg) p.o. 6 hourly for 10 days (see Antimicrobial guidelines, Appendix 3), with review in 48 h.

Clinical features

• An infection of cutaneous and subcutaneous tissue characterised by erythema, warmth, oedema and tenderness.
  
• Predisposing factors include a break in the skin (e.g. insect bite, trauma) or a pre-existing skin lesion.
  
• May be associated with regional lymphadenopathy, fever, chills and malaise.
  
• It may be associated with deeper involvement including necrotising fasciitis, osteo myelitis and septic arthritis.
  
• Usually caused by Streptococcus pyogenes or Staphylococcus aureus.
  
• Haemophilus influenzae type b (Hib) is uncommon but should be considered in non-immunised children <5 years. It is often accompanied by bacteraemia or meningitis, or both.

Diagnosis

Cultures of blood, skin aspirate or skin biopsy are positive in about 25% of cases.

Management

• Flucloxacillin 25 mg/kg (max. 500 mg) p.o. 6 hourly.
  
• Parenteral therapy is needed if there is fever, rapid progression, lymphangitis or lymphadenitis. Non-immunised children <5 years with facial cellulitis should be treated with cefotaxime 50 mg/kg (max. 2 g) i.v. 6 hourly, and flucloxacillin.

Gram-positive bacteria (group A â-haemolytic streptococci and Staphylococcus aureus) can cause disease as a result of production of protein (superantigen) toxins.

Clinical features

Fever, erythematous rash, conjunctivitis, reddened mucous membranes, strawberry tongue and prolonged capillary refill time. A range of clinical presentations may be seen. At the most severe end of the spectrum, capillary leak leads to hypotension, shock and multi-organ failure (toxic shock syndrome).

This condition may also be associated with the use of tampons and specific information should be sought.

Diagnosis

Early diagnosis depends on recognition of clinical features. Culture results may help to confirm the diagnosis later.

Management

A critical part of early management is to remove any possible focus of infection (including retained tampon if appropriate).

Early recognition of shock with appropriate fluid management and intensive care is important. Antibiotics should include an anti-staphylococcal agent (e.g. flucloxacillin 50 mg/ kg (max. 2 g) i.v. 4 h, see Antimicrobial guidelines). Treatment should also include clindamycin (to inhibit bacterial toxin and host cytokine production) and i.v. immunoglobulin (as an immunomodulatory agent).

Cause

Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV).

Transmission

Perinatal (vertical) transmission is the most common mechanism of paediatric HIV infection.

Incubation period

It is important to distinguish between infection with HIV, which may be asymptomatic during a variable latent period, and the progressive immunological derangement that leads to AIDS. Perinatally infected infants may be asymptomatic for several months or years.

Risk groups

• Infants of mothers who are known to be HIV positive or who are members of a high-risk group (e.g. sex workers, i.v. drug users and those with bisexual partners).
  
• I.v. drug users.
  
• Men who have sex with men.
  
• Sexual contacts (including sexually abused children) of individuals with HIV.
  
• Transfusion recipients, particularly patients with congenital bleeding disorders who received blood products before 1985.
  
• Individuals from countries with a high prevalence of HIV infection.

Clinical features

Clinical presentations of HIV infection include prolonged fever, failure to thrive or weight loss, generalised lymphadenopathy, hepatosplenomegaly, parotitis, chronic or recurrent diarrhoea, recurrent otitis, chronic candidiasis and chronic eczematous rash.

The indicator diseases for the diagnosis of AIDS in children include candidiasis, lymphoid interstitial pneumonitis, recurrent episodes of serious bacterial infection, opportunistic infection (e.g. Pneumocystis carinii pneumonia and disseminated Mycobacterium avium complex disease), CMV retinitis, cerebral toxoplasmosis, progressive neurological disease and malignancy (e.g. primary brain lymphoma).

Diagnosis

Patients (± their families) require counselling and informed consent before testing for HIV, which should be done on a confidential basis. Specific antibody detection is a sensitive indicator of HIV infection in adults and children, but passively transferred maternal antibodies may persist for up to 18 months in infants. Prior to 18 months, ultra sensitive HIV PCR is the best available test to confirm the diagnosis of HIV infection. The disease is monitored using a combination of CD4+ T-cell count and quantification of HIV RNA (viral load). Patients may also have lymphopaenia, abnormal T-cell subsets and hypergammaglobulinaemia.

Management

A multidisciplinary approach by a specialised team is vital for the unique needs of these patients and their families. Medical management of HIV-positive patients includes:

• Antiretroviral drugs (highly active antiretroviral treatment, HAART).
  
• Prevention of opportunistic and other infections (immunisation and prophylactic antimicrobials).
  
• The early diagnosis and aggressive management of opportunistic infections.

Control

Antiretroviral therapy given to the HIV-infected woman during pregnancy and delivery, and to the newborn, complete avoidance of breast-feeding (where formula is available and safe) and with other measures can decrease the rate of transmission to the child from 25–35% to <2%. Recognition of HIV-infected pregnant women is therefore critical.

Antiretroviral therapy and other interventions (e.g. immunisation, Pneumocystis prophylaxis) can have a significant impact on disease progression.

Community acquired needle-stick injuries

The risk of sero conversion to HIV, HBV or HCV from a community-acquired needle-stick injury is very low. Exposed individuals should be reassured. Immunity to hepatitis B should be confirmed, and if incomplete, hepatitis B vaccine should be given. Unless the injury is considered to be particularly high risk, no further management is required at the time. Follow-up should be arranged for counselling and serology if required. Tetanus toxoid ± immunoglobulin should be considered.

Occupational needle-stick injuries

Standard precautions

• All sharp objects and body fluids should be considered as potentially contaminated.
  
• Avoid contact with blood and other body fluids by:
  

  – Using protective barriers (e.g. gloves) if contact is likely.

  
  

  – Immediately cleaning up accidental spills.

Managing needle-stick injury or exposure to blood/blood-stained body fluid