Associate Professor Rohan Ameratunga
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1 Associate Professor Rohan Ameratunga Adult and Paediatric Clinical Immunologist and Allergist Auckland 8:30-9:25 WS #87: Infections in Children - An Immunologist's View 9:35-10:30 WS #99: Infections in Children - An Immunologist's View (Repeated)
2 The child with recurrent infections
3 Recurrent infections in children Too many Too severe Too long Not responding to treatment
4 Recurrent Infections in children Globally
5 Malnutrition in the world
6 Childhood deaths in the world
7 Main categories Normal child 50% Child with atopy 30% Child with chronic disease and/or anatomical problems 10% Immunodeficiency: primary or secondary 10%- detailed features when to suspect
8 Clinical investigation History detailed history incl pregnancy Examination Investigations- identifying PID Lab and imaging studies
9 Pregnancy history Infections Drug use legal or illegal HIV risk factors Tobacco
10 Birth history Length of gestation Neonatal complications Admission to PICU Any complications in hospital
11 Prematurity Increased risk of RSV in the first year Difficult to identify which subgroups are at most risk Palivizumab Immunoglobulins transferred in the last trimester Increased risk of other infections not as well documented
12 Prematurity Bronchopulmonary dysplasia Still an issue with surfactant, reduced oxygen, changes in ventilation strategy etc
13 Cost-effectiveness of palivizumab in New Zealand. Vogel A, McKinlay M, Ashton T, Lennon D, Harding J, Pinnock R, Graham D, Grimwood K, Pattemore P, Schousboe M. J Paediatr Child Health 2002 Aug;38(4):
14 Growth and development Chronic disease- poor growth, some PIDS Heart and lung disease eg CF GI disease eg diarrhoea
15 Reactions to immunisation Adverse reactions to live vaccines eg rotavirus, BCG Polio no longer live
16 Medications Steroids immunosuppressives
17 Family history Recurrent infections Early deaths Unexplained deaths in childhood Consanguinity Ethnicity
18 Normal child 50% 4-8 infections/yr Increased risk: sibling attending daycare Overcrowding no more than 1 pneumonia or 2 OM in the first three years of life. Generally viral infections Complete recovery between infections
19 Socioeconomic factors and recurrent infections in children The worried well Socio-economic status- Overcrowding Attendance at daycare Number of siblings Birth order Access to medical care
20 Socioeconomic factors and recurrent infections in children
21 Normal infections
22 Clinical features of concern More than two severe infections/ yr 3 respiratory infection incl sinusitis Abx > 2 months/yr Failure to respond to antibiotics Need for IV antibiotics Unusual complications eg empyema, mastoiditis, abscesses
23 Parental smoking and other risk factors for wheezing bronchitis in children. Rylander E, Pershagen G, Eriksson M, Nordvall L. Eur J Epidemiol 1993 Sep;9(5): children with wheezing. 309 controls Parental smoking rr 1.8 Strongest association with maternal smoking and children,18/12
24 Parental smoking, bronchial reactivity and peak flow variability in children Cook, Derek G; Strachan, David P Thorax 1998;53(4):
25 Recurrent wheezy bronchitis and viral respiratory infections. Mertsola J, Ziegler T, Ruuskanen O, Vanto T, Koivikko A, Halonen P. Arch Dis Child 1991 Jan;66(1): pts 1-6 yrs recurrent wheezy bronchitis 115 episodes Mycoplasma 52 Rhinovirus 34 Associated with parental smoking
26 Atopic child AR mistaken for sinusitis Bronchitis vs pneumonia PID or anatomical problems can co-exist with atopy Higher risk of atopy with some PIDS May have allergen specific IgE tests in PID
27 Allergy as a cause of recurrent infections in children 5yr old boy with recurrent muco-purulent nasal discharge. Requiring up to 12 Rx antibiotics per year Symptoms worse in winter Frequent sneezing and rhinorrhoea Other family members also atopic Strongly +ve spt tests to HDM, cats
28 Allergy as a cause of recurrent infections in children Allergy treatment HDM prevention measures Combination of Butacort and Loratadine Reduction in frequency of infections and rhinitis symptoms Allergen-specific immunotherapy
29 The prevalence of atopic disorders in children with chronic otitis media with effusion. Alles R, Parikh A, Hawk L, Darby Y, Romero JN, Scadding G Pediatr Allergy Immunol 2001 Apr;12(2): chronic OME cases from an ENT clinic 89% had allergic rhinitis (hx, spts) cf 20% prevalence of allergic rhinitis
30 Child with chronic disease 10% Barrier failure Inadequate respiratory clearance Obstruction CV problems Foreign body Resistant organism Continuous reinfection eg contaminated water
31 Host factors important in defense Skin Mucous membranes Lysozyme Digestive enzymes Respiratory mucous clearance mechanisms
32 Generalised anatomical factors predisposing to recurrent infections in children Skin defects eg burns, eczema Multiple mechanisms: barrier loss, nutritional compromise, secondary immune defects, use of antibiotics, nosocomial infections, immobility Infections in multiple anatomical areas
33
34 Cystic fibrosis Most patients identified by neonatal screening Can present later Children can look relatively well Nasal polyps in children Chronic cough, chronic sputum production, clubbing Sweat testing +/- genetic testing Genetic testing
35 Localised anatomical factors predisposing to recurrent infections in children Localised defects eg Bronchial obstruction Most infections in the same system and same location Infections may be slow to respond to Rx There may be localised complications eg bronchiectasis. Investigations and management focused on correcting the anatomical defect.
36 Lobar pneumonia
37 Localised anatomical factors predisposing to recurrent infections in children Localised defects eg enlarged adenoids Frequent URTIS and OME ENT referral if suspected. Surgery +/- tympanostomy tubes
38 Localised anatomical factors predisposing to recurrent infections in children Localised defects eg chronic tonsillitis ENT referral Removal if indicated Frequent cause of ill health, URTIS, abdominal symptoms etc Foreign bodies- unilateral nasal symptoms
39 The immune response to cancer
40 Infections in cancer Destruction of the immune system esp Leukemia Drugs- chemotherapy Radiotherapy- multiple mechanisms Localised obstruction eg Ca bronchus Malnutrition Probably worse with hematological malignancy
41 Suspected immunodeficiency 10% Family history of immunodeficiency or unexplained early death (eg, before age 30 years) Failure to gain weight or grow normally (failure to thrive) Need for intravenous antibiotics and/or hospitalization to clear infections Six or more ear or respiratory tract infections/ year Two or more serious sinus infections or pneumonias within one year Four or more new ear infections within one year Two or more episodes of sepsis or meningitis in a lifetime Two or more months of antibiotics with little effect
42 Suspected immunodeficiency Recurrent or resistant oral or cutaneous candidiasis Recurrent deep skin or organ abscesses Infection caused by an unusual microbe and/or in an unusual location Complications from a live vaccine (eg, rotavirus, varicella, and BCG vaccines) Chronic diarrhea Nonhealing wounds Extensive skin lesions Persistent lymphopenia (age dependent) Unexplained autoimmunity or fevers Granulomas Hemophagocytic lymphohistiocytosis (HLH) Lymphoma in infancy Features typical of syndromic PIDs
43 Primary immune deficiency Stem cell Hematopoeisis X X Thymus BM X X X X antigen X X Th2 Th1 CD8 CD4 IgA IgG IgM
44 WHO classification of primary immune deficiency B cell defects- Bruton s, CVID, XLA T cell defects- di George Combined defects- SCID, XHIM Other well-defined disorders- WAS Complement defects Phagocytic defects- CGD Disorders of innate immunity- TLRs Autoinflammatory disorders- FMF, TRAPS Disorders of Apoptosis- ALPS Phenocopy
45 Patients with PID by Reported Diagnosis Other Ataxia Wiskott-Aldrich DiGeorge Hyper IgM CGD 1% 1% 2% 2% 4% 12% Severe Combined X-Linked Agamma 4% 8% IgA Subclass IgG Subclass Common Variable 17% 24% 34% 0% 10% 20% 30% 40% Source: IDF Patient Survey N=2815
46 When to suspect primary immune deficiency Increased # of infections Unusual organisms Unusual site of infections Failure to respond as predicted Failure to thrive/ growth retardation Other clinical features Family history
47
48 Times Hospitalized before Diagnosis % 21+ 5% % None 30% % One 17% Source: IDF Patient Survey N=2,708
49 Possible presentations of PID ID: GI: Chest: Bronchiectasis, bronchitis Rheum: SLE (comp), Oligoarthritis ENT: Sinusitis, otitis media Endo: Haem: AIHA, tcp, lymphoma Onc: Lymphoma, SCC Rec bacterial, fungal, viral infections Chronic diarrhea with Giardia, Crypto Mucocutaneous Candidiasis
50
51 Recognition of PIDs Institution of correct therapy Prevention of complications Addressing issues related to chronic disease (marriage, work, school, support IDFNZ) Genetic implications for family members
52 Health Status: Before and 80% After Treatment 70% 60% 50% 40% 30% 29% 28% Good Very Good Excellent 20% 10% 0% 11% 4% 4% Year Before Diagnosis 16% Last Year on IVIG
53 Why Patient was Initially Tested for PID Other Overwhelming Infection Unusual Infection 8% 6% 11% Repeated Infections 66% Routine Checkup Family History 1% 7% 0% 20% 40% 60% 80%
54 PID: Typical history 2yr old boy Recurrent chest infections since 6 mo Frequent OM Family history: 2 uncles died at 1 yr of age OE/ Absent tonsils Inx IgG 1.2 g/l No response to specific vaccines
55 Some examples of primary immune deficiencies T cell B cell Combined (HIV), digeorge Bruton s, CVID SCID, XHIM, Complement C1inh Neutrophil CGD, LAD
56 T cell immune defects T cell immune defects eg digeorge syndrome Infections: viral, fungal, parasitic, protozoal Impaired growth in children
57 B cell immune defects B cell immune defects eg XLA (Brutons) Infections: bacterial, protozoal, (viral) Normal growth in children
58 Chronic sinusitis
59 Chronic sinusitis
60 Bronchiectasis
61
62
63 Giardia
64 IVIG
65 Screening tests for immune deficiency FBC ESR Blood film Immunoglobulins Specific antibodies: proteins eg tetanus toxoid Specific antibodies: carbohydrates blood group HIV test
66 Interpretation of immunoglobulin levels Age of the child Prematurity Concurrent infections Medication Lab-lab variations
67 Interpretation of immunoglobulin levels
68 Advanced tests for PID Vaccine responses Flow cytometry Electron microscopy Molecular diagnosis
69
70 Summary: An approach to the child with recurrent infections Accurately document the numbers of infections Are the infections localised to 1 organ system? Are they localised to one anatomical location? Are there obvious predisposing factors? Incl smk Failure to thrive/ growth retardation? Unusual features of the infections Relevant Family history
71 Main categories Normal child 50% Child with atopy 30% Child with anatomical problems 10% Immunodeficiency: primary or secondary 10%
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