Lincoln Solomon Severe pertussis infections in children

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Lincoln Solomon Severe pertussis infections in children

BORDETELLA PERTUSSISFastidiousGram-negativeAerobicCoccobacillusHuman ‘respiratory’ pathogenDroplet spreadhttp://children.webmd.com/pertussis-whooping-cough-10/slideshow-prevent-pertussis


PERTUSSIS / WHOOPING COUGHToxin mediated• Adhesins– Filamentous hemagglutinin(FHA)– Pertactin– Fimbriae– Tracheal colonisation factorColonisationCiliated epitheliumProliferationEffects:• Pathogenic• Cilia dysfunction• Airway inflammation• Inhibit chemotaxis• Lymphocytosis• Exotoxins– Pertussis toxin (PTx)– Adenylate cyclase– Type III secretion system– Dermonecrotic toxin– BrkAB– LPS– Tracheal cytotoxin– BvgAS systemADP Ribosylation of hostcell G-ProtensC-AMP synthesis, antiinflammatoryEpithelial cell damagePro-inflammatory• Immunogenic• FHA• Pertactin• Fimbriae• PTxComponentsof acellularpertussisvaccinesAdapted from: Preston A Bordetella pertussis: the intersection of genomics and pathobiology Canadian Medical Association Journal - Volume 173, Issue 1 (July 2005)


CLINICALClassic stages1. Incubation 6 to 21 days2. Catarrhal 1 to 2 weeks – mostinfectious, non-specific3. Paroxysmal 3 to 6 weeks -- lessinfectious, but more ‘toxic’4. Convalescence monthsWHO Case definition– Dr makes diagnosis• Clinical:– cough ≥ 2 weeks AND paroxysms– OR post-tussive vomit– OR whoop• ±Lab Confirmation:– Culture OR Serology OR PCR• WHO-recommended surveillance standard of pertussis• http://www.who.int/immunization_monitoring/diseases/pertussis_surveillance/en/index.html< 3 monthsGagging, GaspingChoking, CyanosisApneaApparent life-threatening eventSIDSLong: Principles and Practice of Pediatric Infectious Diseases, 4th ed


THE PROBLEMResurgence world-wideLaura L. Myers Reuters Jul 20USA:California 2010 …9000 cases 10 infant deaths2012 multistate epidemic … 18 000 casesWashington … > 3000Wisconsin … > 3000New York …970AustraliaUK


THE PROBLEMHighest death rates among < 1 year oldsNot yet or incompletely immunised


SEVERE PERTUSSIS IN PICUUK1998 to 2000• N = 25• 16 < 2 months old• 2 deaths• Cough 92%– DURATION (days) mean 15.2, median 8.5– Paroxysms 58%• Vomit 60%• Fever 44%• Apnoea 68%• Cyanosis 44%• Pneumonia 20%• Conjunctival bleed 4%Crowcroft N S Arch Dis Child 2003;88:802–806Singapore2001 to 2007• N = 45– 8: HCU, 3: ICU• Mean age: 4.1 months• 0 deaths• Cough 51%– DURATION >3 weeks– Paroxysms 47%• Fever 26%• Apnoea 2%• Cyanosis 13.3%• Recurrent desats 6.6%• Poor feeding 4.4%Goh A et.al Vaccine 29 (2011) 2503–2507


SEVERE PERTUSSIS IN PICU• Melbourne– 20 year retrospective• 1985 to 2004– N=49• median age 6 wk• apnea ± cough paroxysms 63%• pneumonia 18%– longer stay– higher wcc– higher mortality n=7• 6 needed circulatory support, 4ECMO• seizures 10%Namachivayam P et.al. Pediatr Crit Care Med 2007; 8:207–211• Aukland– 12 year audit• 1991 to 2003– N=72• 81% < 3months old• Reason for PICU admission– Apnoea 82%– Bradycardia 63%– Pneumonia 28%• Deaths 4– Repeated desaturation 24%– Intubated pre-arrival 13%– Respiratory arrest 11%– Seizures or encephalopathy 10%– Shock 8%– Cardiopulmonary arrest 7%Surridge J et.al. Arch Dis Child 2007;92:970–975


BLOEMFONTEIN• Ongoing prospective case series* of all childrenhospitalised with B.pertussis or B.parapertussisidentified on nasopharyngeal swabs by• PCR detection of gene sequences:– IS481 B.pertussis– IS1001 B.parapertussis*Hallbauer et al. 2011WHOOPING COUGH AND OTHER BORDETELLA INFECTIONSERIK L. HEWLETTDescribe• Clinical picture• ICU Resource Usage• OutcomePCR + for B.pertuss or B.parapertussis admitted to PICUs of Bloemfontein Academic HospitalComplex• 2008 to July 2012


T: 051 401 9111 info@ufs.ac.za www.ufs.ac.zaSeptember 18, 2012


PRESENTATIONSymptoms• Cough 86.8%– Duration (days)• Mean 4.3, Median 3• Range of 1 to >30 (one infant)– Paroxysmal 2• Post-tussive vomiting 34.2%• Apnoea 28.9%• Fever 15.8%• Difficult breathing 12• Diarrhea 4• Convulsions 3• Tachycardia 2• Whoop 1• Stridor 1• Poor feeding 1• Excessive salivation 1Indications for PICU admission• respiratory failure 84%• cardiovascular dysfunction 29%• apnoea 26%• convulsions 13%• air leak syndromes 6%• myocarditis 3– Raised CK and CK MB fractions• hypoglycaemia 2• pneumonia 2• CMV Pneumonitis 1• shock 3• cardiorespiratory arrest 3• severe pre-renal failure 1On admission Mean Median RangeTotal WCC 21.7 17.4 2.2 to 69.4LymphocyteCountNeutrophilcount9.7 6.9 1.4 to 449.4 9.5 0.13 to 8.6


PICU RESOURCE USAGEMechanical ventilation• 71%• Duration (days)– Mean 9.3– median 8– range 2 to 27Inotropic support 21 (55.2%)• dobutamine 7• dopamine 4• both agents 9• adrenaline + dobutamine + dopamine 1• adrenaline + dobutamine 1• dobutamine + dopamine + digoxin 1peritoneal dialysis 1LOS(days)ICUTotal 367 667mean 12 22Median 11 16Hospitalrange 3 to 38 3 to 74partial exchange transfusions 1


COMPLICATIONSSepsis 15– MRSA 1– Coag neg staph 9– Acinetobacter 2– Candida tropicalis 1– Stenotropohmonas 1– Strep viridans 1CVS dysfunction 10Convulsions 6Pneumothorax 5– Pneumomediastinum 3Apnoea 4?Hyperviscocity 2– WCC 72 and 75Anaemia 21– needing ≥1 RBC transfusionMyocarditis 2ARDS 1UTI 1Hyponatraemia 1Pulmonary haemorrhage 1Hyperlactataemia 2Hypocalcaemia 2Lung atelectasis 1Recurrent Pneumothorax 1


DEATHS• 1 male• Ages 10, 11, 12 and 13weeks• HIV negative• ICU LOS:– 3, 6, 13, 20 daysPresenting symptomsCough duration:4 , 2 5 21 daysApnoea 1Whoop 1Difficult breathing 2Fever 1Excessive salivation 1Maximum white cell countTotal Neutro Lympho32 11.97 15.28 175.5 18.04 41.63 151 13.76 22.3 121.66 18.5 2.7 2ICU DayIndications for ICU admissionRespiratory failure 1Resp failure + shock 2Apnoea + convulsions + pre-ICU cardiac arrest 1


DEATHSMechanical ventilation duration(days)Inotropes– 3 in two infants– 11 and 20 (one each).• Dobutamine 5 days• Dobutamine 4 days + dopamine 2days• Dobutamine 20 days + Adrenaline4 days• All three 2 daysComplications• Cardiovascular failure 2• Coag neg Staph sepsis 1• Multiple RBC transfusions 2• UTI 1• ARDS 1• Probable hyperviscocity 1– (WCC 75 with 41.6lymphocytes)• Pre-mortem hyperlactataemia (10),hyperkalaemia and hypocalcaemia. 1Causes of Death• Respiratory failure 2• Refractory shock 1• Nosocomial sepsis + multi-organ failure 1


CONCLUSIONSSevere Pertussis in Bloemfontein26% of hospital diagnosed cases with PCR + for PertussisPresentation on admission atypicalWHO case definitions do not always applyGreatest burden of disease morbidity and mortality among < 16 week age groupIncompletely or not yet vaccinatedProlonged ICU and hospital stayConcomitant morbidities / complications and mortalityPrevention is less costly than cure …1 full vaccine schedule v.s. 1 ICU day: R1330* vs R2200RecommendationsGreater coverage with standard vaccination schedule2009 DPT vaccine coverage Free State: 78.5%*Vaccinate:women of child bearing age / close contacts of newborns / adolescents / elderly / HCWChemoprophylaxis:prevent spread from case contacts*Visser et.al SAMJ, vol.101 no.8 Cape Town Aug. 2011


T: 051 401 9111 info@ufs.ac.za www.ufs.ac.za

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