After reading this chapter you should:
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be able to assess, diagnose and manage infections acquired in the UK and overseas
Infections acquired in the UK
Infections present at all ages, in any organs and can cause mild or life-threatening illness. They can present with symptoms that are nonspecific, particularly in younger infants, where it can be difficult to distinguish between viral and bacterial infection. Clinical presentation may be the direct result of the causative infection or the sequelae of that infection. The management, therefore, should aim to address the presenting clinical problem of the patient, identify the responsible organism and anticipate the possible consequences of that infection.
Bacterial Infections
Bacterial Septicaemia
Sepsis is caused by the immune response of the body to an infecting organism—usually bacterial—although it can be caused by viral or fungal infections. The normal body response to sepsis leads to inappropriate vasodilatation of vessels, increased vascular permeability, white cell proliferation and abnormal cell signalling. If left untreated, it can develop into septic shock, with a significant morbidity and mortality from multiorgan failure.
Children with an isolated bacteraemia will usually present with a pyrexia of unknown focus along with nonspecific malaise. Those with meningococcal disease will often develop a rash that may initially be morbilliform before rapidly becoming petechial and purpuric. Signs of severe sepsis may develop rapidly and include:
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hypotension and shock with cool or mottled extremities
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weak pulse; delayed capillary refill
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confusion
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rigors
The most common organisms are Staphylococcus aureus including methicillin-resistant strains (MRSA), Streptococcus pneumoniae , Streptococcus pyogenes and Escherichia coli . Children who have asplenia are at risk of overwhelming infection from encapsulated bacteria including pneumococcus, meningococcus, H. influenzae and salmonella.
Investigations
It is important to obtain full blood count, C- reactive protein, blood cultures (obtained prior to starting antibiotics), renal function tests, liver function tests, clotting studies, glucose and lactate.
Treatment and management
Bacterial sepsis requires prompt treatment with urgent resuscitation. Antibiotics must be administered as soon as possible and certainly within one hour from attending the clinical area as delays beyond this time period will lead to a significant increase in mortality. Patients are likely to need significant fluid volumes, blood products and intensive care (with ventilatory support) if in septic shock. The monitoring of patients once admitted should follow a structured approach using a Paediatric Early Warning System (PEWS) to identify any potential deterioration.
If subsequent culture results isolate a specific organism, then a full investigation should be undertaken to identify the source including unusual sites such as mastoid area, sinuses, bones and heart. Secondary seeding of distant sites may cause infections such as septic arthritis, meningitis and endocarditis.
Potential complications
These include:
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high mortality rate
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hypoxic seizures and brain injury leading to disability
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extremity loss (limbs, ears, nose tips) from initial coagulopathy and poor perfusions
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adrenal haemorrhage (Waterhouse-Friderichsen syndrome)
Bacterial meningitis
Meningitis is a medical emergency and any children or young person with symptoms and signs suggestive of the diagnosis need immediate treatment. The recognised findings are fever, headache, photophobia, confusion and nuchal rigidity. In younger children, symptoms can be nonspecific with irritability, reduced conscious level, poor feeding and apnoea.
Signs of raised intracranial pressure include a bulging fontanelle, hypertension with bradycardia, papilloedema, abnormal posturing and localised neurological signs and these indicate the need for an urgent response.
The most common organisms are identified in children are:
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Streptococcus pneumoniae
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Neisseria meningitidis
Immunisation programmes in many countries have seen a marked reduction in meningitis caused by Haemophilus influenzae type b (Hib) and pneumococcal disease.
The common organisms in those under 3 months of age are:
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Escherichia coli
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Group B streptococcus
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Listeria monocytogenes
Those patients with an identified CSF leak (basal skull fractures, those with indwelling shunts or cochlear implants) are at risk of pneumococcal meningitis ( Table 12.1 ).
| Appearance | WCC | PMN | Lymph | Protein g/l | Glucose mmol/l | |
|---|---|---|---|---|---|---|
| Normal | Clear | 0–5 10 6 /l | 0–2 10 6 /l | 0–5 10 6 /l | 0.15–0.45 | 2.2–4.4 |
| Bacterial | Cloudy | >500 | 90% | Low initially | Raised | <2.2 |
| Viral | Clear | <1000 | Rise later | raised | <1 | Normal |
| Tubercular | Fibrin web | 100–500 | Normal | raised | 0.1–0.5 | low |
Investigations
The diagnosis is made by CSF microscopy and culture ( Table 12.1 ) and there should be a low threshold for performing a lumbar puncture particularly in the younger age group where there is a lack of localising signs. The procedure would not be needed if the classical meningococcal rash and signs of sepsis were present, and there are also clinical situations where a lumbar puncture would be contraindicated. Microscopy of CSF fluid would usually show bacteria, although these may not be evident if there was partial treatment with antibiotics. In this situation, subsequent CSF culture may be negative and PCR may offer further information. Full blood count, CRP, blood culture, coagulation screen, glucose, electrolytes and liver function tests are necessary initial investigations. Should it be necessary to delay the lumbar puncture for imaging, then antibiotics must be given after the blood culture is obtained.
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signs of raised intracranial pressure
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GCS less than 9 or acute deterioration in GCS
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shocked patient
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suspected meningococcal septicaemia with spreading petechial rash
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within 30 minutes of a seizure
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following focal seizures and a persistent focal neurology
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severe coagulopathies
Treatment and management
Patients with a possible meningitis need prompt treatment with IV antibiotics and the current UK guideline advises ceftriaxone for those over 3 months whilst those under this age should have cefotaxime plus amoxicillin or ampicillin to cover a potential Listeria infection. The administration of intravenous dexamethasone is advised if:
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purulent CSF
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high CSF white count (greater than 1000/microlitre)
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bacteria on gram stain
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high protein count (greater than 1gm/litre)
The administration of fluids and the monitoring of electrolytes are important and require frequent review and those with features suggestive of raised intracranial pressure will need a fluid-restricted plan. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a recognised complication and can make fluid management challenging.
Many children will make a full recovery but some may develop deafness, seizures, neurodevelopmental disability and hydrocephalus. Sadly, some may die. A follow-up review should be made and a hearing assessment requested within 4 weeks of discharge.
Pneumococcal infections
Streptococcus pneumoniae is a capsulated, gram-positive diplococcus and multiple serotypes exist. Carriage in school-age children is up to 60% and even higher during winter months.
Overwhelming pneumococcal infection can occur in those with:
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functional or anatomical asplenia
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B-cell and complement deficiency
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immunosuppression
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cochlear implants
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base of skull fracture
There is an increased risk of disease with intercurrent viral respiratory infection such as influenza, parainfluenza, human metapneumovirus, respiratory syncytial virus or adenovirus, with peaks during winter months. There are few contraindications to vaccination with the conjugate vaccine and its introduction has led to a significant reduction on incidence of invasive disease.
Pneumococcus causes four main clinical problems:
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pneumonia (see Chapter 17 Respiratory)
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meningitis
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bacteraemia
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otitis media (see Chapter 18 ENT and Hearing)
Invasive disease usually follows a bacteraemia, but occasionally local spread can occur. Invasive pneumococcus and acute meningitis are both notifiable diseases.
Meningococcal disease
There are 12 capsular serotypes and the commonest serotype in the UK is type B (up to 80%), with C, W135 and Y the source of less common disease. Asymptomatic carriage is between 5% to 11% in adults and up to 25% in adolescents. This figure increases dramatically in outbreaks, particularly in crowded close contact environments such as university accommodation or residential schools. Spread is by close contact with infected respiratory secretions. Certain travel destinations are considered a high-risk source for meningococcal disease and include Mecca for the Hajj pilgrimage and sub-Saharan Africa. Vaccination against Serotypes A, B, C, W and Y is given in the UK immunisation schedule.
Meningococcal disease typically presents with meningitis, septicaemia ( Figure 12.1 ) or both although other sites can lead to myocarditis, endocarditis, arthritis, pneumonia and chronic meningococcaemia. Meningitis and septicaemia are discussed above.
Streptococcal disease
Streptococci are divided into those which produce in vitro haemolysis (alpha, beta or gamma) and Lancefield groups. The organism produces tissue damaging factors such as streptolysins, hyaluronidase, DNase and exotoxin. Activated cytokines lead to shock, organ failure and death and are responsible for many of the manifestations of severe invasive streptococcal disease. Group A streptococcus is the most significant pathogen and is a normal inhabitant of the nasopharynx. Incidence is highest in school-age individuals, in winter and in areas of crowding and close contact but asymptomatic carriage of streptococci is common as it tends to colonise throat and skin ( Table 12.2 ).
| Classification | Example | Commonly associated diseases |
|---|---|---|
| Group A (beta haemolytic) | S. pyogenes | pharyngitis, tonsillitis, wound and skin infections, septicaemia, scarlet fever, pneumonia, rheumatic fever, glomerulonephritis, necrotising fasciitis |
| Group B (beta haemolytic) | S. agalactiae | sepsis, postpartum or neonatal sepsis, meningitis, skin infections, endocarditis, septic arthritis, UTIs |
| Group C, G (beta haemolytic) | S. equi and S. canis | pharyngitis, pneumonia, cellulitis, pyoderma, erysipelas, impetigo, wound infections, puerperal sepsis, neonatal sepsis, endocarditis, septic arthritis |
| Viridans (alpha or gamma) | many including S. anginosus | endocarditis, bacteraemia, meningitis, localized infection, abscesses |
Streptococci produce disease by local invasion, toxin production and nonsuppurative sequelae. The commonest presentations are pharyngitis, skin infections and scarlet fever.
Pharyngitis is a common condition and fever and sore throat may be caused by both bacterial and viral infections. Those with a streptococcal pharyngitis will usually present with:
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acute sore throat and tonsillar exudates
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fever
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cervical lymphadenitis
These findings can also be seen in Epstein-Barr virus which can lead to difficulties in diagnosis. Local spread of streptococcus may lead to sinusitis, mastoiditis or pharyngeal and peritonsillar abscesses. However, a throat swab that is positive for streptococcus may simply reflect carriage rather than invasive disease.
Scarlet fever occurs secondary to toxin production and usually presents with pharyngitis followed, within 48 hours, by a rash which starts in the groin, neck and axillae and spreads over the trunk before fading after 3–4 days. On close inspection, the rash has small papules and is often described as ‘sandpaper-like’ and is the result of a delayed skin reaction to the exotoxin. Circumoral pallor, a white coated ‘strawberry tongue’ and desquamation of palms and fingers are all common findings. On clinical grounds, the condition may be indistinguishable from Kawasaki disease but a shorter duration of pyrexia and the lack of mucous membrane involvement will be more suggestive of streptococcal infection.
Investigations
Streptolysin O is produced by Group A streptococci and antibody titres (ASOT) can be measured in blood but this does not help with diagnosis of acute infection. It is only some weeks later when a rise of greater than twofold between samples taken in the acute phase (week 1) are compared with those taken in the convalescent phase (weeks 2–4) that is considered diagnostic of recent infection. Confirmation of a current infection will come from blood culture or tissue samples of infected sites.
Treatment and management
Management of acute pharyngitis is usually conservative and antibiotics are not given as most infections are due to a viral cause. Children with a proven streptococcal pharyngitis or with classical scarlet fever are treated with phenoxymethylpenicillin or clarithromycin. Treatment of pregnant women is aimed at preventing early Group B streptococcal disease (GBS) but has no effect on late GBS morbidity and mortality.
Potential complications
These can be suppurative or nonsuppurative in nature. Suppurative complications include otitis media, tonsillar abscess, pneumonia, meningitis, cerebral abscess, endocarditis and osteomyelitis. Nonsuppurative complications are delayed effects and immunologically mediated and include acute rheumatic fever and poststreptococcal glomerulonephritis.
Staphylococcal infections
Staphylococcus aureus is a gram-positive aerobic organism and its marked pathogenicity is due to its virulence, potential toxin production and its ability to develop antibiotic resistance.
Transmission is usually by hand-to-hand contact or nasal discharge. Neonates are particularly susceptible due to the umbilical stump, thin epidermis and poor defences. Handwashing is the most effective preventative measure whilst topical antibiotics (mupirocin) and topical washes can be used to decrease carriage rates.
Common sites of infections include blood, skin, bones, joints and heart whilst less common sites are lung and meninges. Exotoxin production is responsible for staphylococcal scalded skin syndrome ( Figure 12.2 ), toxic shock syndrome and acute gastroenteritis.
Septic arthritis presents with a hot, swollen joint with restricted movement and decreased function. It is unusual to have infection in more than one joint, so multiple joint involvement should suggest a reactive or inflammatory arthritis. Direct sampling from the joint is necessary to confirm diagnosis and guide antibiotic treatment.
Osteomyelitis usually presents with localised bony pain, tenderness and redness over the affected area. Initial plain films may be normal and a periosteal reaction may only become evident at a later stage and so MRI usually provides more immediate information.
A preseptal orbital cellulitis presents with pain, redness and swelling of the eyelid and anterior soft tissues. An ophthalmology opinion would be important to exclude a more deep-seated infection which may produce restricted eye movements or severe proptosis. MRI should be performed if any doubt about orbital involvement.
Endocarditis is presented in Chapter 16 Cardiology.
A 5-year-old girl was admitted with a 2 day history of fever, malaise and vomiting. She was previously well. No other family members had a febrile illness. On admission, her temperature was 38.3 o C, BP 110/65 and GCS was 13. There was no obvious rash. Photophobia and neck stiffness were confirmed.
A clinical diagnosis of meningitis was made and a full infection screen was undertaken including lumbar puncture. She was started on intravenous antibiotics. Initial CSF results showed raised white cell and protein values and low glucose compared with plasma glucose. CSF culture results became available at 12 hours and showed E. coli and S. millerii .
The microbiology team was clear that this was not a contaminant and advised more detailed investigations to identify a possible route of entry for the organisms. Repeat examination noted a ‘sacral pit’.
Further investigations were undertaken to identify possible entry sites including ENT review for potential sinus defects and MRI of spine and sacrum. The MRI identified a dermal sinus—a type of spinal dysraphism. She was referred to colleagues in paediatric neurosurgery for surgical correction.
Pertussis
Bordetella pertussis and Bordetella parapertussis are gram-negative bacilli that remove the cilia in the major airways. It is this loss of the ‘ciliary escalator’ and the dependence on coughing to clear the airway which accounts for the symptoms and protracted nature of the illness.
A mild prodrome of fever, coryza, and occasional cough occurs early in the clinical picture but progresses to the paroxysmal cough followed by a whoop or a vomit whilst infants may also present with apnoea. The cough may persist for up to 10 weeks and is typically worse at night. Illness caused by Bordetella parapertussis is usually less severe than that of Bordetella pertussis.
Alternative diagnoses and differing features
In younger infants, bronchiolitis may initially be mistaken for whooping cough although the coughs are very different in each. In older children, a viral (adenovirus) or bacterial pneumonia can produce similar symptoms whilst inhalation of a foreign body, thoracic lymphadenopathy and poorly controlled asthma with nighttime cough should be considered.
Investigations
Diagnosis is made by culture from a nasal swab and although this is the gold standard investigation, it is typically not reported in time to be clinically useful. A marked lymphocytosis may support the clinical diagnosis and is known to be an independent predictor of fatality from the infection. PCR and serological testing may be used although IgG to Bordetella may simply indicate either a past infection or vaccination.
Treatment and management
This is primarily supportive as an infant may become exhausted and fail to maintain respiratory effort or adequate oral intake. Antibiotics will only decrease infectivity and not reduce the duration of the paroxysmal phase of the disease.
Potential complications
These include subconjunctival haemorrhage, pneumonia, pneumothorax, seizures and alkalosis secondary to tussive vomiting. In overwhelming infection with extensive symptoms, there is the potential for hypoxic brain injury and death.
Important sequelae
Pertussis is part of the routine vaccination schedule and now offers an acellular vaccine produced from fragmented organisms. There are few contraindications. Due to concerns raised in the 1970s about a possible link between cellular vaccines and neurodevelopmental problems, the parents of children with an emerging neurological condition are still advised to consider a delay to immunisation until the neurological problem has been fully investigated. Immunisation in pregnancy has been introduced recently due to a number of outbreaks with the aim of increasing maternal IgG and placental transfer.
Lyme disease
Ticks transfer the causative organism of Lyme disease, Borrelia burgdorferi , when they bite the host. The prompt removal of the tick reduces the risk of transmission of the bacteria although removal of the embedded tick requires a specific technique to ensure all parts of the insect are removed. Infected ticks are found throughout the UK and high-risk areas include wooded areas in Scotland, New Forest and the Lake District.
Children and young people present with:
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fever, fatigue, lymphadenopathy
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muscle aches, migratory arthralgia
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unexplained cranial nerve palsies
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cognitive impairment—memory problems and difficulty concentrating
Erythema migrans, often at the site of a tick bite ( Figure 12.3 ), is the pathognomonic rash of Lyme disease and, if identified, no further investigations are needed. It can appear between 1 to 4 weeks after a tick bite and can last for several weeks.
Investigations
There is no gold standard diagnostic test to confirm Lyme disease although serological testing may be recommended by the local microbiology team.
Treatment and management
The choice of antibiotic depends on the age of the child and clinical features but either oral doxycycline or amoxicillin are recommended as the first-line treatment. If CNS disease identified then the patient should receive intravenous ceftriaxone. There is a potential for long-term problem with chronic arthritis in infected individuals.
Pharmacological agents used
Doxycycline causes staining and dental hypoplasia in growing teeth and should only be given to children over the age of 12 years.
Tuberculosis
Mycobacterium tuberculosis (TB) is spread from person to person through the air and primarily affects the lungs leading to pulmonary TB. Most infected individuals remain asymptomatic although most have a latent infection which becomes active within the first two years after exposure.
The individual with latent TB is usually detected by contact tracing from a known infected individual. Those with pulmonary TB will present with:
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malaise
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cough
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loss of appetite
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weight loss
Examination of the chest may show signs of parenchymal (reduced breath sounds, crackles) and pleural (effusion) involvement. Extrapulmonary TB could include any system and the symptoms at presentation would vary. TB meningitis is one such site and individuals would have the same symptoms and signs of someone with bacterial meningitis.
Investigations
A range of investigations are used to clarify the possible diagnosis of TB.
Mantoux test is an indirect assessment to show immunity against Mycobacterium TB but it does not differentiate between active and latent TB and a negative test does not rule out the active disease. The test site on the skin needs a follow-up examination to interpret the response.
Interferon Gamma Release Assay (IGRA) has the advantage that there is no need for the child to return for the review of the test but, again, does not differentiate between active and latent TB. The assay is less accurate in those under 2 years of age and hence Mantoux is preferred in this group. The test is also useful in the assessment in patients who had previously received a BCG immunisation.
Chest radiograph will show hilar or mediastinal lymphadenopathy along with a peripheral focus that are indicative of active infection whilst other radiological findings include patchy consolidation, pleural effusion, nodular infiltration and less commonly cavitating lesions and miliary dissemination.
Early morning sputum samples and gastric aspirates can be obtained and stained for acid fast bacilli before being cultured. A positive culture is only seen in around 30% to 40% and can take up to 40 days to be available and so would not be helpful in the early stages of management.
GeneXpert MTBRIF® is a PCR-based assay which gives information within a few hours on positive samples. It can also detect the main genetic mutation for rifampicin resistance.
Diagnosis of latent TB infection is based on a positive Mantoux or IGRA in an asymptomatic child with a normal CXR. The diagnosis of pulmonary TB usually comes from clinical suspicion and hilar lymphadenopathy on the chest radiograph whilst a diagnosis of extrapulmonary TB requires a high index of suspicion and investigations tailored according to the site. CNS infection will require neuroimaging and CSF analysis.
Treatment and management
An asymptomatic child with a positive Mantoux and a normal CXR would receive a 12-week course of isoniazid and rifampicin.
A symptomatic child or one who has an abnormal CXR should be assumed to have active TB and further investigations are warranted. It is imperative that all the diagnostic samples are collected before starting TB treatment although treatment can start before culture results are available. The standard TB regime is for a total 6 months (26 weeks) with four drugs for the first 2 months (isoniazid, rifampicin, pyrazinamide, ethambutol) followed by 4 months of isoniazid and rifampicin.
TB meningitis requires a 12 month course with 2 months of quadruple therapy and 10 months of isoniazid and rifampicin. Steroids should be added in CNS TB and pericardial TB.
Relevant pharmacological agents used
Isoniazid —may cause hepatoxicity, peripheral neuritis or Stevens Johnson Syndrome.
Rifampicin —may cause hepatoxicity, turns urine and all body fluids red (must inform patient), induces liver enzymes and can increase metabolism of oestrogens and anticoagulants.
Pyrazinamide —good meningeal penetration
Ethambutol —can affect visual acuity which corrects if drug stopped
Non tuberculous mycobacterium
Atypical mycobacterial disease is the result of infection from mycobacteria other than Mycobacterium tuberculosis or Mycobacterium leprae . The most common type seen in well children would be Mycobacterium avium which may lead to a cervical lymphadenitis ( Figure 12.4 ). The patient is usually well and presents with an erythematous cervical mass which is usually nonpainful. Surgical excision alone usually leads to full resolution.
