Infection and immunity Flashcards
When assessing a febrile child, what questions should you consider?
How is fever identified in children? How old is the child? Are there risk factors for infection? How ill is the child? Is there a rash? Is there a focus for infection?
How is fever measured in children in hospital?
The parents will usually know but in hospital:
<4 wks old by an electronic thermometer in the axilla
4 weeks to 5 years by an electronic thermometer in the axilla or infrared tympanic thermometer
What type of infection in febrile infants <3 months old?
Often present with non-specific symptoms and have bacterial infection, uncommon to have viral infection due to passive immunity from their mother. Unless a clear cause is shown, require urgent sepsis screening and IV antibiotics
What are some risk factors for infection>
Illness of other family members
Prevalence of illness in the community
Unimmunised
Recent travel abroad, e.g. malaria, typhoid
Contact with animals e.g. brucellosis
Increased susceptibility due to immunodeficiency
What are some red flags suggesting serious illness in the febrile child?
Fever >38 if under 3 months, >39 if 3-6 months
Colour - pale, mottled, blue
Reduced LOC, neck stiffness, bulging fontanelle, status epileptics, focal neurological signs and symptoms
Significant respiratory distress
Bile-stained vomiting
Severe dehydration/shock
What does it mean if there is no focus for infection?
If no focus is identified, it may be because it is the prodromal phase of a viral illness, but may indicate serious bacterial infection, especially UTI or septicaemia
What is the main cause of a febrile child?
Upper respiratory tract infection (URTI), check for otitis media
How can you confirm meningitis?
Inflammatory cells in the CSF.
Are most meningitis infection bacterial or viral?
Viral, most are self-resolving. Bacterial is more serious (5-10% mortality).
What is the serious pathophysiology of meningitis?
Inflammatory mediators are released and leucocytes are activated, together with endothelial damage, this leads to cerebral oedema, raised ICP and decreased cerebral blood flow. The inflammatory response below the meninges causes a vasculopathy resulting in cerebral cortical infarction, and fibrin deposits may block the resorption of CSF by the arachnoid villi, resulting in hydrocephalus
What bacteria is most likely to cause meningitis in <3 month olds?
Group B strep
E.coli
Listeria monocytogenes
What bacteria is most likely to cause meningitis in 1 months -6 year olds?
Neisseria meningitidis
Strep pneumoniae
Haemophilus influenza
What bacteria is most likely to cause meningitis in > 6 years?
Neisseria meningitidis
Strep pneumoniae
What are some common differential diagnoses for the febrile child?
URTI Otitis media Tonsilitis Stridor Pneumonia Septicaemia Seizure Periorbital cellulitis Rash UTI Meningitis
What may you get in a history of meningitis/encephalitis?
Fever Headache Photophobia Lethargy Poor feeding/vomiting Irritability Hypotonia Drowsiness Loss of consciousness Seizures
What might you get during examination in meningitis/encephalitis?
Fever Purpuric rash Neck stiffness (not always in infants) Bulging fontanelle in infants Opisthotonus (back arching) Positive Brudzinski/Kernig signs Signs of shock Focal neurological signs Altered conscious level Papilloedema
What investigations would you do when thinking of a diagnosis of meningitis?
Bloods: FBC, glucose, blood gas, coagulation screen, CRP, culture of blood, throat, urine, stool
Rapid antigen test of meningitis organisms
LP for CSF unless contraindicated
What is Brudzinski sign?
Flexion of the neck with the child supine causes flexion of the knees and hips
What is Kernig sign?
With the child lying supine and with the hips and knees flexed, there is back pain on extension of the knee
What are some contraindications to lumbar puncture?
Cardiorespiratory instability
Focal neurological signs
Signs of raised ICP (coma, high BP, low heart rate)
Coagulopathy
Thrombocytopaenia
Local infection at the site of LP
If it causes undue delay in starting antibiotics
What is the first thing you do if you suspect meningitis?
There should be no delay in the administration of antibiotics and supportive therapy. A third-generation cephalosporin (cefotaxime or ceftriaxone) is the preferred choice.
What are the cerebral complications of meningitis?
Hearing loss Local vasculitis Subdural effusion Local cerebral infarction Haemophilus influenzae Hydrocephalus Cerebral abscess
How does meningitis cause hearing loss?
Inflammatory damage to the cochlear hair cells
How does meningitis cause hydrocephalus?
It may result from impaired resorption of CSF (communicating hydrocephalus) or blockage of the ventricular outlets by fibrin (non-communicating hydrocephalus)
How is meningitis spread prevented?
Prophylactic treatment with rifampicin to eradicate nasopharyngeal carriage is given to all household contacts for meningococcal meningitis.
What proportion of CNS infections are viral?
2/3rds
What are the main viruses that cause viral meningitis infection?
Enteroviruses, EBV, adenoviruses and mumps
How does viral meningitis compare to bacterial meningitis?
It is usually less severe and a full recovery can be anticipated
How can a diagnosis of viral meningitis be confirmed?
Culture of PCR of CSF; culture of stool, urine, nasopharyngeal aspirate, throat swabs and serology
What are the uncommon pathogens that cause meningitis?
Mycoplasma or Borrelia burgdorferi or fungal infection. More common in immunodeficient children.
What is encephalitis?
Whereas in meningitis there is inflammation of the meninges, in encephalitis there is inflammatory of the brain substance.
In general, what causes encephalitis?
Direct invasion of the cerebrum by a neurotoxic virus (HSV)
Delayed brain swelling following a disordered neuroimmunological response to an antigen, usually a virus (after chickenpox)
A slow virus infection, such as HIV
What are the changes in the CSF during meningitis?
Bacterial: very high polymorphs and protein and very low glucose
Viral: high lymphocytes, normal/high protein, normal/low glucose
What are the changes in the CSF during encephalitis?
Normal/high lymphocytes, normal/high protein, normal/low glucose
How do children with encephalitis often present?
Fever, altered consciousness and often seizures
What are the most common organisms that cause encephalitis?
Enteroviruses, respiratory viruses and HSV.
If HSV has not been excluded as a cause of encephalitis what should be your first step?
Start high-dose aciclovir
What organisms can cause toxic shock syndrome?
Staph aureus and group A strep
What are the clinical features of toxic shock syndrome?
Fever >39 degrees
Hypotension
Diffuse erythematous, macular rash
How do the toxin-producing organisms in toxic shock syndrome cause the syndrome?
The toxin can be released from infection at any site, including small abrasions or burns, which may look minor. The toxin acts as a super antigen and, in addition to the main features of toxic shock syndrome, causes other organ dysfunction
Apart from the main clinical features in toxic shock syndrome what other organ dysfunction can occur?
Mucositis (conjunctivae, oral mucosa, genital mucosa)
GI (vomiting/diarrhoea)
Renal impairment
Liver impairment
Clotting abnormalities and thrombocytopaenia
CNS (altered consciousness)
How would you treat toxic shock syndrome?
Areas of infection should be surgically debrided. Antibiotics often include ceftriaxone together with clindamycin.
What is necrotising fasciitis?
A severe subcutaneous infection, often involving tissue planes from the skin down to fascia and muscle. The area may enlarge rapidly, leaving poorly perfused necrotic areas of tissue, usually at the centre.
What are the clinical features of nec fasc?
There is severe pain and systemic illness, which may require intensive care
What are the main organisms causing nec fasc?
Staph aureus or group A strep
How would you treat nec fasc?
IV antibiotics alone is not enough. Surgical intervention and debridement of necrotic tissue is needed to stop spread of infection. IV immunoglobulin may also be given
What are the characteristic features of the meningococcal rash?
Non-blanching on palpation, irregular in size and outline and have a necrotic centre
What conditions can be caused by Strep pneumoniae?
Pharyngitis, otitis media, conjunctivitis, sinusitis as well as pneumonia, bacterial sepsis and meningitis
What conditions can be caused by haemophilus influenzae type b?
Otitis media, pneumonia, epiglottitis, cellutitis, oestomyelitis and septic arthritis and meningitis
What increases your susceptibility of pneumococcal infection?
Hyposplenism (sickle cell disease and nephrotic syndrome)
What is impetigo?
A localised, highly contagious, staphylococcal and/or streptococcal skin infection, most common in infants and young children.
When is impetigo more common?
Where there is pre-existing skin disease, e.g. atopic eczema.
How does impetigo present?
Lesions are usually on the face, neck and has and begin as erythematous macules, which may become vesicular/pustular or even bullous. Rupture of the vesicles with exudation of fluid leads to the characteristic confluent honey-coloured crusted lesions.
How is impetigo spread around the body?
It is readily spread to adjacent areas and other parts of the body by auto inoculation of the infected exudate.
How do you treat impetigo?
Topical antibiotics (mupirocin) are sometimes effective for mild cases. Narrow-spectrum systemic antibiotics (flucloxacillin) are needed for more severe infections. Affected children should not go to nursery or school until the lesions are dry
What are boils?
Infections of hair follicles or sweat glands, usually caused by staph aureus.
How do you treat boils?
Systemic antibiotics and occasionally surgery.
How does periorbital cellulitis present?
There is fever with erythema, tenderness and oedema of the eyelid. It is almost always unilateral. It may follow local trauma to the skin or spread from a nasal sinus infection or dental abscess
How do you treat periorbital cellulitis?
Promptly with IV antibiotics to prevent posterior spread to orbital cellulitis.
What is orbital cellulitis?
Propotosis, painful or limited ocular movement and reduced visual acuity. It may be complicated by abscess formation, meningitis or cavernous sinus thrombosis
What is scalded skin syndrome?
An exfoliative staphylococcal toxin which causes separation of the epidermal skin throughout the granular cell layers.
How does scalded skin syndrome present?
It affects infants and young children, who develop fever and malaise and may have a purulent, crusting, localised infection around the eyes, nose and mouth with subsequent widespread erythema and tenderness of the skin. Areas of epidermis separate on gentle pressure, leaving denuded areas of skin, which subsequently dry and heal without scarring
How do you treat scalded skin syndrome?
IV anti-staph antibiotic, analgesia and monitoring fluid balance
What are some viral causes of a maculopapular rash?
HHV (human herpes virus) 6 or 7 in < 2yrs Enteroviral rash Parvovirus 'slapped cheek' Measles Rubella
What are some bacterial causes of a maculopapular rash?
Scarlet fever (group A strep) Erythema marginatum (rheumatic fever) Salmonella type (typhoid, classic rose spots) Lyme disease - erythema migrans
What are some non-viral or bacterial causes of a maculopapular rash?
Kawaski disease
Juvenile idiopathic arthritis
What are some viral causes of a vesicular, bullous and pustular rash?
Varicella-zoster (chickenpox, shingles)
HSV
Coxsackie (hand, foot and mouth)
What are some bacterial causes of a vesicular, bullous and pustular rash?
Impetigo (characteristic crusting) Boils (infection of sweat gland) Staphyloccocal bullous impetigo Staphylococcal scalded skin Toxic epidermal necrosis
What are some non-viral or bacterial causes of a vesicular, bullous and pustular rash?
Erythema multiforme
Stevens-Johnson syndrom
What are the bacterial causes of a petechial, purpuric rash?
Meningococcal, other bacterial sepsis
Infective endocarditis
What are some viral causes of a petechial, purpuric rash?
Enterovirus and other viral infections
What are some non-viral or bacterial causes of a petechial, purpuric rash?
HSP
Thromocytopaenia
Vasculitis
Malaria
How does herpes simplex virus enter the body?
Usually through the mucous membranes or skin, at the site of the primary infection may be associated with intense local mucosal damage.
Is HSV1 or HSV2 associated with mouth or genital infection?
HSV1 is usually associated with lip and skin lesions.
HSV2 with genital lesions, but both viruses can cause both types
How do you treat HSV?
Aciclovir, a viral DNA polymerase inhibitor.
What is gingivostomatitis?
The most common form of primary HSV illness in children (usually 10 months to 3 years).
How does gingivostomatitis present?
There are vesicular lesion on the lips, gums and anterior surface of the tongue and hard palate, which often pogress to extensive, painful ulceration with bleeding. There is a high fever and the child is very miserable. It may persist for 2 weeks.
What are the skin manifestations of HSV?
Eczema herpeticum - wide-spread vesicular lesions develop on eczematous skin
Herpetic whitlows - painful, erythematous, oedematous white pustules on the site of broken site on the fingers.
What eye disease can HSV cause?
Blepharitis, conjunctivitis, corneal ulceration and scarring, leading to loss of vision
What CNS disease can HSV cause?
Aseptic meningitis and encephalitis
What are the clinical features of chickenpox (Varicella zoster)?
200-500 lesions start on head and trunk, progress to periphery. Appear as crops of papule, vesicles with surrounding erythema and pustules at different times for up to week.
What are the complications of chickenpox?
Bacterial superinfection - staphylococcal, streptococcal, may lead to toxic shock syndrome or nec fasc
CNS - cerebellitis, generalised encephalitis, aseptic meningitis
Immunocompromised - haemorrhagic lesions, pneumonitis, progressive and disseminated infection, DIC
How would you treat chickenpox?
Treatment is not normally needed, IV aciclovir in immunocompromised children
What is shingles?
It is caused by reactivation of latent varicella-zoster virus, causing vesicular eruption in the dermatomal distribution of sensory nerves (shingles)
Where does shingles most often occur?
Most commonly in the thoracic region, although any dermatome can be affected
In which children, is shingles more common?
In those who had primary infection in the first year of life
What does recurrent or multidermatomal shingles suggest?
A T-cell immune defect
What are the clinical features of Epstein-Barr virus?
Fever, malaise, tonsillopharyngitis (often severe, limiting oral ingestion of fluids and food), lymphadenopathy (prominent cervical lymph nodes), petechiae on the soft palate
How would you diagnose EBV?
Atypical lymphocytes (number large T cells seen on blood film); a positive monospot test; seroconversion with production of IgM and IgG to EBV antigens
How long do symptoms of EBV last?
They may persist for 1-3 months but ultimately resolve.
How do you treat EBV?
Treatment is symptomatic. When the airway is severely compromised, corticosteroids may be considered.
What should you NOT use to treat EBV and why?
Ampicillin or amoxicillin may cause a florid maculopapular rash in children infected with EBV and should be avoided.
How is EBV transmitted?
Usually oral contact
How is cytomegalovirus usually transmitted?
Via saliva, genital secretions or breast milk and more rarely via blood products, organ transplants and transplacentally
How does CMV differ from EBV on investigations?
Patients may have atypical lymphocytes on the blood film but are heterophile antibody-negative.
How can you treat CMV?
You can treat it with ganciclovir or foscarnet, but both have serious side-effects
What can parvovirus cause?
Aplastic crisis in haemolytic anaemias (e.g. sickle cell) or the fetus (causes hydrops)
What are the clinical features of measles?
Fever, cough, runny nose, conjunctivitis, marked malaise, Koplik spots, maculopapular rash
How does the measles rash present?
It spreads downwards from behind the ears, to the whole of the body. Discrete, maculopapular rash initially, becomes blotchy and confluent.
What are Koplik’s spots?
White spots on buccal mucosa, seen against bright red background
What are some respiratory complications of measles?
Pneumonia
Secondary bacterial infection and otitis media
Tracheitis
What are some nerulogical complications of measles?
Febrile convulsions
EEG abnormalities
Encephalitis 8 days after onset
Subacute sclerosing panencephalitis rare but devastating
What are some non-respiratory or neurological complications of measles?
Diarrhoea Hepatitis Appendicitis Corneal ulceration Myocarditis
How do you treat measles?
Symptomatically. Isolate these children in hospital. Ribavirin may be used in immunocompromised children.
What are the clinical features of mumps?
Incubation period - 15-24 days. Onset is with fever, malaise and parotitis (uncomfortable, main complain of earache or pain on eating and drinking). The fever usually disappears with 3-4 days.
What would you find on investigation of mumps?
Plasma amylase level are often elevated.
What are some complications of mumps?
Viral meningitis and encephalitis and orchitis
How does rubella present?
The prodrome is usually mild with a low-grade fever. There is a maculopapular rash , appearing first on the face then spreading centrifugally to cover the whole body, disappears in 3-5 days. In children, it is not itchy. Lymphadenopathy.
What are some complications of rubella?
Arthritis, encephalitis, thrombocytopaenia and myocarditis.
What is Kawasaki disease?
A systemic vasculitis.
What age children does Kawasaki disease usually affect?
6 months to 4 years old, with a peak at the end of the first year.
What are some infective causes of a prolonged fever?
Localised infection Bacterial infections (typhoid) Deep abscesses (intra-abdominal, retro-peritoneal, pelvic) Infective endocarditis TB Viral infections (EBV, CMV, HIV) Parasitic infections (malaria)
What are some non-infective causes of a prolonged fever?
Systemic juvenile idiopathic arthritis Systemic lupus erythematosus Vasculitis (Kawasaki) IBD Sarcoidosis malignancy (leukaemia, lymphoma)
What are the clinical features of Kawasaki disease?
Fever >5 days (possible inflammation of BCG vaccination) 4 of 5 of these: Conjunctival infection Mucous membrane changes Cervical lymphadenopathy Rash (polymorphous) Extremities
What mucous membrane changes may occur during Kawasaki?
Pharyngeal infection; red, dry, cracked lips; strawberry tongue
What would you find on investigating Kawasaki disease?
High CRP, ESR, WCC with a platelet count that rises typically in the second week of the illness
What are the complications of Kawasaki disease?
Coronary artery aneurysms and sudden death
How would you treat Kawasaki disease?
Prompt treatment with IV immunoglobulins. Aspirin. Potentially even long-term warfarin. Persisten inflammation and fever may require treatment with infliximab (anti-TNF alpha monoclonal antibodies), steroids or ciclosporin
What are the clinical features of TB?
Prolonged fever, malaise, anorexia, weight loss or focal signs of infection, CXR changes
What test is performed if TB is suspected?
Mantoux test, a history of BCG immunisation needs to be taken into account. Also a Interferon-gamma release assay (IGRA)
How would you treat TB?
Triple or quadruple therapy (rifampicin, isoniazid, pyrazinamide, ethambutol). After puberty, pyridoxine is given weekly to prevent the peripheral neuropathy associated with isoniazid therapy.
Where can post-primary TB present?
Bones, joints, kidneys, pericardium and CNS
