Infection and Immunity Flashcards
What counselling should be given to parents with an unvaccinated children?
- Understand why they have not vaccinated – let them talk for however long they need
- Give examples of how the infections can cause long-term morbidity/mortality
- Mumps → infertile boys, deafness
- Rubella → severe deformities to pregnancy
- Measles → death
- Polio → massive respiratory problems
What are the long-term morbidity/mortality of mumps?
- Infertility in boys
- Deafness
What are the long-term morbidity/mortality of measles?
Death
What are the long-term morbidity/mortality of rubella?
Severe deformities to pregnancy
What are the long-term morbidity/mortality of polio?
Massive respiratory problems
What are the congenital and neonatal infections?
- Toxoplasmosis
- Other - Syphilis, Parvovirus, VZV, HIV, HBV
- Rubella
- CMV
- HSV
What is the management of toxoplasmosis in a child?
- 1st line = Pyrimethamine + Sulfadiazine for 1 year
- Adjunct = Prednisolone
What is the management of syphilis in a child?
- IM benzathine penicillin
What is the management of syphilis in a child?
- IM benzathine penicillin
What is the management of CMV in a child?
- IV ganciclovir
- Oral valganciclovir
What is the management of herpes simplex virus in a child?
-
Aciclovir (400mg, TDS) if neonate exposed on delivery
- If not nothing is needed
What can GBS cause in a neonate?
- Pneumonia
- Meningitis
- Septicaemia
What is the management of sepsis in a neonate?
- Early onset <72 hours = IV cefotaxime + amikacin + ampicillin
- Late onset >72 hours = IV meropenem + amikacin + ampicillin
What is the management of GBS in an adult?
- Only for women in labour → IV benzylpenicillin
How does a mother pass listeria monocytogenes to a child?
- Passes to child in placenta → mother has a mild influenza-like illness
What are the consequences of listeria in a mother?
- Spontaneous abortion
- PTL
- Neonatal sepsis
What are the signs and symptoms of listeria monocytogenes?
- Meconium staining of liquor in pre-term infant
- Widespread rash
- Sepsis
- Pneumonia
- Meningitis
- Mortality 30%
What is the management of listeria monocytogenes?
- IV amoxicillin/ampicillin OR Co-trimoxazole
- If systemic infection = IV benzylpenicillin + gentamicin
Define Kawasaki Disease.
Systemic vasculitis in a child under the age of 4/5 years old.
What are the risk factors for Kawasaki disease?
- Ethnicity - Japanese, Black-Caribbean
- Peak at 1yo
What are the signs and symptoms of Kawasaki disease?
-
Fever for over 5 days +4/5 of the following CRASH symptoms
- Conjunctivitis
- Rash - polymorphous; begins hands/feet
- Adenopathy = Cervical lymphadenopathy
- Strawberry tongue = Mucous membrane changes
- Hands & feet swollen - desquamate/peel
What are the complications of Kawasaki disease?
- Cardiovascular
- Gallop rhythm
- Myocarditis
- Pericarditis
- Coronary aneurysms → require long-term warfarin and close follow-up
- Sudden death
What are the appropriate investigations for suspected Kawasaki disease?
- Diagnosis on clinical findings (no test)
- Bloods - FBC (inc. platelets), CRP, ESR
- Echocardiography - check cardiac function
What is the management of Kawasaki disease?
- Admission
- IVIG (within 10 days)
-
High-dose aspirin - reduce thrombosis risk
- Other = corticosteroids, infliximab/ciclosporin and plasmapheresis if persistent inflammation and fever
What causes malaria?
- Protozoa Plasmodium
- Falciparum most fatal
- Ovale, Malariae and Vivax
- Spread by female Anopheles mosquito
What are the signs and symptoms of malaria?
- Onset 7-10 days after inoculation (<1yr)
- Cyclical fever
- Diahorrea and vomting
- Flu-like symptoms - shaking, chills, night sweats, headache, myalgia
- Jaundice
- Anaemia
- Thrombocytopaenia
What are the appropriate investigations for suspected malaria?
-
3 thick and thin blood films
- Thick = parasite
- Thin = species, parasitaemia
- Malaria rapid antigen detection tests - plasmodial HRP-II, parasite LDH
What is the prevention of malaria?
- Anti-malarial prophylaxis with quinine
- Bite prevention – repellent and nets
What is the management of malaria?
- Arrange immediate admission → Medical emergency
- Notify PHE (can have a RAPID deterioration)
- Treatment
- Non-falciparum = Chloroquinine
- Mild falciparum (not vomiting, parasitaemia <2% and ambulant)
- 1st line = ACT (Artemisinin Combination Therapy)
- 2nd line = Atovaquone-proguanil (cannot give doxycycline to age <12yo)
- Severe/complicated falciparum
- 1st line = IV Artesunate
- 2nd line = IV Quinine
- Primaquine for eradication of hypnozoites - dormant parasites in liver in vivax and ovale
What can anti-malarial drugs precipitate?
G6PDD
What are the causes of typhoid fever?
- Salmonella typhi
- Paratyphoid
- Both via faeco-oral transmission
What are the complications of typhoid fever?
- GI perforation
- Myocarditis
- Hepatitis
- Nephritis
What are the signs and symptoms of typhoid fever?
- Fever
- Bradycardia
- Headache
- Travel history
- Dry cough
- Weight loss/Anorexia
- Malaise
- Myalgia
- GI symptoms - diarrhoea or constipation
- Splenomegaly
- Bradycardia
- Rose-spots on trunk
What are the appropriate investigations for suspected typhoid fever?
- Blood culture = Diagnostic
- Bloods – FBC, LFTs, stool culture
What is the cause of Dengue fever?
Dengue arbovirus
What are the signs and symptoms of dengue fever?
- Primary infection:
- Headache (retro-orbital)
- Fine erythematous sunburn-like rash (50%)
- High fever and myalgia
- Recent ravel history - 5 day incubation period
- Hepatomegaly
- Abdominal distension
- Severe = Haemorrhage
What is Dengue haemorrhagic fever?
-
Secondary infection
- Previously infected child → subsequent infection with a different strain → severe capillary leak, hypotension, haemorrhagic manifestations
- Treatment = fluid resuscitation usually helps a lot
- Due to partially effective host immune response augmenting the severity of the infection
What are the appropriate investigations for suspected dengue fever?
- Gold standard = PCR viral antigen, serology IgM
- bloods
- FBC - low WCC, low platelets, low Hb → espe in severe
- LFTs
- Serum albumin
What is the management of dengue fever?
- Supportive → fluids and monitoring
- ITU - if increased deterioration
How is mumps transmitted?
- Transmission by respiratory secretions
- Long incubation period (15-24 days)
What are the signs and symptoms of mumps?
- Asymptomatic (in 30% of cases)
- Parotid swelling - infectious 5 days before and after
- Headache
- Fever
- Pancreatitis
- Neuritis
- Arthritis
- Mastitis
- Nephritis
- Thyroiditis
- Pericarditis
What are the appropriate investigations for suspected mumps?
- Oral fluid IgM sample
- Amylase is raised in the blood
What is the management of mumps?
- Notify HPU
- Isolate for 5 days from time of parotid swelling
- Supportive care
- Rest
- Analgesia
- Fluids
- Safety net for complications:
- Mumps orchitis → infertility (very rare)
- Viral meningitis → encephalitis (very rare)
- Deafness (unilateral and transient)
What causes mumps?
Mumps paramyxovirus
What are the signs and symptoms of measles?
-
Prodrome = high fever, irritability, conjunctivitis/coryza
- Febrile convulsions
- Maculopapular rash - infectious 4 days before and after
- Koplik spots
- Cough
- No lymphadenopathy
What are the appropriate investigations for suspected measles?
- 1st line = Measles serology (IgM and IgG) from Oral Fluid Test
- 2nd line = PCR of blood or saliva
What is the management of measles?
- Notify HPU
- Isolate for 4 days after development of rash - children in hospital
- Rest and supportive treatment
- Fluids
- Antipyretics
- Rest
- Immunise close contacts and encourage vaccination after acute episode
- Safety net the complications:
- Encephalitis
- Sub-acute Sclerosing Panencephalitis
- Otitis media
- Pneumonia
- Keratoconjunctivitis
What is Sub-acute sclerosing panencephalitis?
Measles dormant in the CNS
- S/S = Dementia and Death
What is the cause of rubella?
Togavirus
What are the signs and symptoms of rubella?
- Prodrome = mild fever or asymptomatic
- Pink maculopapular rash that fades in 3-5 days - infectious 1 week before and 5 days after
- 20% → Forchheimer spots (red spots on soft palate)
- Lymphadenopathy - suboccipital, postauricular
What are the appropriate investigations for suspected rubella?
- 1st line = Rubella serology (IgM and IgG) from Oral Fluid Test
- 2nd line = RT-PCR
What is the management of rubella?
- Notify HPU
- Isolate for 4 days after development of rash
- Supportive
- Fluids
- Analgesia
- Rest
- Safety net the complications – haemorrhagic complications due to thrombocytopenia
What are the signs and symptoms of parvovirus?
- 1st = Asymptomatic or coryzal illness for 2-3 days
- Latent for 7-10 days
- 2nd = Erythema infectiosum
- Red ‘slapped cheek’ rash on face - fever, malaise, headache, myalgia - infectious 10 days before and 1 day after rash
- Progresses (1 week later) to maculopapular like rash in trunk and limbs
What are the appropriate investigations for suspected parvovirus B19?
- 1st line = B19 serology (IgM and IgG)
- 2nd line = RT-PCR
What are the complications of parvovirus B19 in children?
-
Aplastic crisis
- Occurs in children with chronic haemolytic anaemia or immunodeficient
-
Fetal disease
- Maternal transmission → leads to fetal hydrops, death due to severe anaemia
What is the management of parvovirus B19?
- Supportive
- Fluids
- Analgesia
- Rest
- No need to stay off school or avoid pregnant women → not really infectious once the rash develops
- Safety net the complications → anaemia, lethargy, pregnancy
What is the cause of chickenpox?
Varicella zoster virus - HHV-3
What are the signs and symptoms of chickenpox?
- Crops of itchy vesicles appear over 3-5 days
- Head, neck, trunk (less on limbs)
- Papule → vesicle → crust
- Infectious 48 hours before and until rash crusted over
- Pyrexia
- Headache
- Abdominal pain
- Malaise
What are the appropriate investigations for suspected chickenpox?
Clinical diagnosis
What is the management chickenpox?
- Supportive
- Fluids
- Analgesia - not ibuprofen
- Rest
- Advice
- Nails short
- Loose clothing
- Isolate (until rash has crusted over or 5 days from onset) from:
- Immunocompromised
- Neonates (<28d old)
- Pregnant women
- Keep home from school
What are the complications of chickenpox?
- Secondary bacterial superinfection - sudden high fever, toxic shock, necrotising fasciitis
- Encephalitis - ataxic with cerebellar signs
- Purpura fulminans - large necrotic loss of skin from cross-activation of antiviral Abs → inhibit the inhibitory coagulation proteins factors C and S → increased clotting and purpuric skin rash
- Dehydration
- Disseminated haemorrhagic VZV
- Pneumonia
- Myocarditis
- Transient arthritis
- Cerebellar atxia
What is the management of chickenpox in immunocompetent adolescents or adults?
Oral aciclovir - 800mg 5/day for 7 days
What is the management of chickenpox in immunocompromised children?
IV aciclovir → oral aciclovir
- Prophylactic prevention = human VZV IVIG
What is the cause of Hand, Foot and Mouth Disease?
- Most common = Coxsackie A16 virus
- Severe = Enterovirus 71
- Atypical = Coxsackie A6
What are the signs and symptoms of hand, foot and mouth disease?
- Painful, itchy, vesicular lesions on hands, foot, mouth, tongue, buttocks
- Some spots in mouth can develop into ulcers
- Mild systemic features
- Fever
- Sore throat
What is the management of hand, foot and mouth disease?
- Supportive - clears up in 7-10 days
- Fluids
- Analgesia
- Rest
- Safety net/Reassure
- Very common under 10 years old
- Report back if:
- Severely dehydration
- If it doesn’t clear up in 2 weeks
- Pregnancy
What causes Roseola Infantum?
- HHV6
-
HHV7 can present very similarly
- HHV6 is more common = Roseola Infantum
- Most children are infected by 2
What are the signs and symptoms of roseola infantum?
- High fever and malaise (3-4 days)
- Generalised macular rash
- Rash starts on neck/body and spread to arms, lasting 1-2 days, non-itchy, blanching
- Febrile convulsions in 10-15%
- Sore throat
- Lymphadenopathy
- Coryzal symptoms
- Diarrhoea and vomiting
- Nagayama spots (spots on the uvula and soft palate
What are the appropriate investigations for suspected roseola infantum?
- HHV6/7 serology (IgG and IgM)
- Rule out measles and rubella serology (similar presentation)
What is the management of roseola infantum?
- Supportive - clears up in a week
- Fluids
- Analgesia
- Rest
- No need to stay off school
- Safety net the complications – high fever → febrile convulsions (10-15%)
What are the appropriate investigations for suspected HIV in a child?
- >18 months = antibody detection (ELISA)
- <18 months = PCR of virus
- Would still have transplacental anti-HIV IgG from mother
- Measured at birth, on discharge, 6 weeks, 12 weeks and finally, at 18 months if mother is HIV +ve
What is the management of HIV in a child?
- Cord clamped as soon as possible and baby bathed immediately after birth
- Low/medium = Zidovudine monotherapy for 2-4w
- High risk = PEP combination (x2 NRTI + x1 INI) for 4w
- Women not to breastfeed
- Give all immunisations including BCG
- Infant testing for HIV at 6 and 12 weeks (at least 2 and 8 weeks after stopping prophylaxis)
What are the examples of T-cell defects in children?
- SCID
- Wiskott-Aldrich syndrome
- DiGeorge syndrome
- Duncan disease
- Ataxia telangiectasia
- HIV
What are the examples of B-cell defects in children?
- SCID
- Bruton’s a-gammaglobulinaemia
- Hyper IgM
- Common variable ID
- IgA deficiency
What are the signs and symptoms of T-cell defects?
- <1 year old
- Severe viral/fungal infections
What are the signs and symptoms of B-cell defects?
- >6 months but <2 year old - IgG
- Severe bacterial infections
What are the examples of neutrophil defects in children?
Chronic granulomatous disease
What are the examples of NK cell defects in children?
- SCID
- Bruton’s a-gammaglobulinaemia
- Hyper IgM
- Common variable ID
- IgA deficiency
What are the examples of leucocyte function defects in children?
- Leucocyte adhesion deficiency
What are the examples of complement defects in children?
- Early complement deficiency (C1, C2, C4)
- Late complement deficiency (C5-C9)
What are the signs and symptoms of neutrophil defects?
- Recurrent bacterial infections
- Invasive fungal infections
What are the signs and symptoms of neutrophil defects?
- Recurrent bacterial infections
- Invasive fungal infections
What are the signs and symptoms of complement defects?
- Recurrent bacterial infections - especially encapsulated bacteria
- SLE-like illness
What are the signs and symptoms of neutrophil defects?
- Recurrent bacterial infections
- Invasive fungal infections
What are the signs and symptoms of Hyper-IgE (Job/Buckley) syndrome?
- Eczema
- Coarse facial features
- Recurrent RTIs
- Cold abscesses
- Candidiasis
What is Ataxia Telangiectasia?
Defective DNA repair
What is associated with ataxia telangiectasia?
Increased risk of Lymphoma
What are the signs and symptoms of ataxia telangiectasia?
- Cerebellar ataxia
- Developmental delay
- Telangiectasia in the eyes
What is Wiskott-Aldrich syndrome?
- X-linked
- Impaired Wiskott-Aldrich gene
- Rare
What are the signs and symptoms of Wiskott-Aldrich syndrome?
- Present at 7 months
- Eczema
- Recurrent infections
- Thrombocytopenia
- Petechiae
- Bloody diarrhoea
- Wiskott-Aldrich Thrombocytopenia Eczema Recurrent infections → may look like ITP
What is the management of Wiskott-Aldrich syndrome?
IVIG → HSCT
What is Duncan disease?
- X-linked lymphoproliferative disease
- Inability to generate a normal response to EBV
What are the signs and symptoms of Duncan disease?
- Death to initial EBV
- Secondary B-cell lymphoma
Describe X-linked SCID.
- 45% of all SCID
- Mutation of common gamma chain on chromosome Xq13.1
- Shared by cytokine receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21
- Inability to respond to cytokines causes early arrest of T cell and NK cell development and production of immature B cells
- Phenotype
- Very low or absent T cell numbers
- Very low or absent NK cell numbers
- Normal or increased B cell numbers but low Igs
What are the signs of SCID?
- Unwell by 3 months of age
- Infections of all types
- Failure to thrive
- Persistent diarrhoea
- Unusual skin disease
- Colonisation of infant’s empty bone marrow by maternal lymphocytes
- Graft versus host disease
- Family history of early infant death
What is DiGeorge syndrome?
- Deletion at 22q11.2 → TBX1 may be responsible for some features
- Usually sporadic rather than inherited
- Normal numbers B cells
- Reduced numbers T cells
- Homeostatic proliferation with age
- Immune function usually only mildly impaired and improves with age
What are the signs of DiGeorge syndrome?
- High forehead
- Developmental defects in the pharyngeal pouch
- Low set
- Abnormally folded ear
- Cleft palate
- Small mouth and jaw
- Hypocalcaemia
- Oesophaegeal atresia
- Underdeveloped thymus
- Complex congenital heart disease
What is Bruton’s X-linked a-gammaglobulinaemia?
- Abnormal B cell tyrosine kinase (BTK) gene
- Pre B cells cannot develop to mature B cells
- Absence of mature B cells
- No circulating Ig after 3 months
What are the signs of Bruton’s X-linked a-gammaglobulinaemia?
- Boys present in first few years of life
- Recurrent bacterial infections
- Otitis media
- Sinusitis
- Pneumonia
- Osteomyelitis
- Septic arthritis
- Gastroenteritis
- Viral, Fungal and Parasitic infections
- Enterovirus, Pneumocystis
- Failure to thrive
What is Hyper IgM syndrome?
-
Mutation in CD40 ligand gene (CD40L, CD154)
- Member of TNF Receptor family
- Encoded on Xq26
- Involved in T-B cell communication
- Expressed by activated T cells but not B cells
- Normal number circulating B cells
- Normal number of T cells but activated cells do not express CD40 ligand
- No germinal centre development within lymph nodes and spleen
- Failure of isotype switching
- Elevated serum IgM
- Undetectable IgA, IgE, IgG
What are the signs of Hyper IgM syndrome?
- Boys present in first few years of life
- Recurrent infections → particularly bacterial
- Subtle abnormality in T cell function predisposes to:
- Pneumocystis jiroveci infection
- Autoimmune diseas
- Malignancy
- Failure to thrive
What is Common variable immune deficiency?
- Heterogenous group of disorders
- Many different genetic defects → many unidentified
- Failure of full differentiation/function of B lymphocytes
- Defined by
- Marked reduction in IgG, with low IgA or IgM
- Poor/absent response to immunisation
- Absence of other defined immunodeficiency
What are the signs of common variable immune deficiency?
- Recurrent bacterial infections
- Pneumonia
- Persistent sinusitis
- Gastroenteritis
- Often with severe end-organ damage
- Pulmonary disease
- Interstitial lung disease
- Granulomatous interstitial lung disease (also LN, spleen)
- Obstructive airways disease
- Gastrointestinal disease
- Inflammatory bowel like disease
- Sprue like illness
- Bacterial overgrowth
- Autoimmune disease
- Autoimmune haemolytic anaemia or thrombocytopenia
- Rheumatoid arthritis
- Pernicious anaemia
- Thyroiditis
- Vitiligo
- Malignancy
- Non-Hodgkin lymphoma
What is Selective IgA deficiency?
- Genetic condition with unknown cause
- Prevalence = 1:600
- 2/3rd = Asymptomatic
- 1/3rd = Recurrent respiratory tract infections