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PERTUSSIS. Pathogenesis,Clinical picture,Lab ∆, treatment & Prophylaxis. By Syed Nafeez. Pathogenesis :. B.Pertussis is an obligate human parasite, surviving only for brief periods outside the host. Source : Early cases,particularly in catarrhal stage Carriers Fomites
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PERTUSSIS Pathogenesis,Clinicalpicture,Lab ∆,treatment & Prophylaxis By Syed Nafeez
Pathogenesis: B.Pertussisis an obligatehuman parasite, survivingonly for briefperiodsoutside the host. Source: Early cases,particularly in catarrhal stage Carriers Fomites Mode of transmission: Inhalation of infectedaerosols (droplet infection) Habit:localized in cilia of resp.epitelium,doesn’tinvade the bloodstream
cilia bacillus Infectedcilia by B.pertussisbacilli
Mechanism: DropletnucleicontainingB.pertussis are inhaled Adherence & rapid multiplication on cilia of resp.epithelium of nasopharynx,trachea & bronchi Liberation of toxins(PT,TCT)& other substances…(FHA,AC) Paralyse ciliacausinginsituΘ of natural defences of resp.tract secondary infections Irritate cells excessive secretions cough & catarrhal sympt Necrosis with polymorphonuclear obstruction of bronchioles ATELECTASIS infiltration diminished oxygenation Interstitial pneumonia,bronchopneumonia contributes to↑frequency of convulsions in infants
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Host response: Humoral response by the production of IgA & pertussistoxinantibodiesis effective. Thesepreventattachment of the bacillus.
Clinicalpicture: Pertussis has an insidiousonsetafter an IP of 1-2 weeks & a protracted course comprising of 3 stages: • Catarrhal stage • Paroxysmal stage • Convalescent stage Each lasting for an approximate of 2 weeks
Catarrhal stage: There’s -low grade fever,malaise -catarrhal symptoms-sneezing, rhinorrhoea & lacrimation -dry,irritatingcough • Duringthis stage the personishighlyinfectious as large number of bacilli are sprayed in the droplets • The diseasecanbearrestedatthis stage by antibiotictreatment but ∆ isverydifficult ‘coz of itsresemblance to typical VIRAL URI witflulikesymptoms.
Paroxysmal stage: • Characterised by distinctive bouts of ↑frequency & intensity of coughthat’s explosive in nature • Duringeachbout,the patient experiences violent spasms of continuouscoughingthatalmostempties the lungsfollowingwhichthere’sdeep inspiration thatproduces the characteristic ‘WHOOP’ • The patient’sexhaustedat the end of eachbout.Posttussivevomiting,cyanosis & convulsions mayoccur.Young infants becomeapnoeic.
About 40-80 bouts occurthroughout the day,moresevereatnight,yieldingthickmucousplugs. • ‘WHOOP’ & major complications occurpredominantly in children • The paroxysmal coughing predominates in olderchildren & adults.
T • Blood changes are distinctive & aid in ∆.There’smarkedLeucocytosiswith an absolutelymphocytosis. TLC-16,000-30,000/μL with 60-80% being lymphocytes lymphocytes in this blood smear from an 18-month-old child with the infection have lobulatednuclei.The cytology of the cells could be mistaken for neoplastic lymphocytes. Lymphocytes with lobulated nuclei
Convalescent stage: There’s ↓frequency & severity of cough. The diseaselasts for 6-8 weeks,thoughitmaybeveryprotracted as in prematureinfants,themalnourished, immunocompromised,peoplewithgeneticsusceptibility.
Complications: Directly by B.pertussis Secondary infections • Pulmonary-pneumonia -scemphysema -atelectasis • Neurological-epilepsy,paralysis • Miscellaneous-haemorrhage(sub-conjunctival,epistaxis) -otitis media -dehydration,malnutrition • In adults-ribfractures,backpain,hearingloss,urinaryincontinence,hernias,rectalprolapse. aspirational
Lab ∆: Specimens: nasopharyngealsecretions blood(serum) for serologicaltesting These are processedthrough: • Culture • Direct Fluorescent Ab testing • Serological techniques-Ab titres,ELISA • PCR
Culture: Nasopharyngealsecretionsrequired for culture are collected by following 4 methods: 1)Cough plate method: • A culture plate of Bordet Gengou GlycerinePotato Blood Agar isheld 10-15 cm infront of patient’smouthduring a bout of spontaneous or inducedcough,suchthat the resp. exudateimpingesdirectly on the medium. • The plate’ssealed & incubated for 48-72 hrs. • Advantageisthat the specimenisinnoculated directly,atbedside.
2)Pernasalswab: • A swab (dacron or calcium alginate) mounted on a flexible nichrome wire, ispassedalong the floor of nasal cavity & materialcollectedfrom the pharyngealwall. • Yields the highest % of isolation.
3)Nasopharyngeal aspiration: • Collectedthrough a soft catheterattached to a syringe • Is the ‘preferred’ specimen. 4)Postnasal/peroralswab: • A cottonswab(West’s post nasal swab) ispassedthroughmouth & secretionsfromposteriorpharyngealwall,collected. • There’spossibility of salivary contamination.
Specimensshouldbeinnoculatedimmediately on BGGPB Agar or its modifications likeLacey’s DFP medium • In case of delay,transport media are used: • 0.25-0.5 ml of Casaminoacidsolution,pH-7.2 • ModifiedStuart’s medium • Mischulow’scharcoal agar • ModifiedRegan-Lowe medium: Is a ½ strengthcharcoal agar supplementedwith 10% horse blood & cephalexin(40mg/L) It Θ growth of nasopharyngeal flora. Is also the medium of choice for culture. • Culture plates are incubated for 7 days at high humidity & temperature of 35-36̊ C . • Should be checked for any growth after 48-72 hrs of innoculation & periodically thereafter.
A positive culture shows the characteristic‘bisectedpearls’ or ‘mercury drop’ colonies. Confluent growth shows aluminium paintappearance • Microscopy shows a non motile,gramnegativebacillus.
Direct FA testing: Used to identify the bacilluseither in direct smears of clinicalspecimens or from culture. • Is inexpensive. • Providesrapiddiagnosis & yields positive resultswhen cultures are negative due to use of antibiotics. • Lacksspecificity & sensitivity due to cross-reactionswithnasopharyngealflora…..hence,unreliable & no longer recommended.
Serological techniques: Focus on identifyingsignificant variations in IgG & IgA titres(upto 4 fold ↑) against relavant B.pertussis virulence factors in both acute & convalescent phases of the disease. • Hence,foraccurate ∆,serumsamples in both phases of disease are to becollected. • Rise in Ab titres isdemonstrated by: • Agglutination not helpful as the rise in agglutinating & • Gel precipitationprecipitating Abs doesn’toccuruntill 3rd week • Complement fixation tests of illness • ELISA-highlyspecific Proposed as diagnostic method in culture sensitive cases A significant ↑ in titres(8E -2fold) between acute & convalescent phase is diagnostic of the disease
PCR: Most sensitivemethod to ∆ Pertussis • Specimenused – nasopharyngeal aspiration • Primers for bothB.pertussis & B.parapertussisshouldbeincluded • Gives positive resultsevenwhen the organismcan’tbecultured. THE BOTTOM LINE: A major problem is the lack of access to diagnostic laboratory methods. Many routine laboratories are not equipped for the diagnosis of B. pertussis infection. This is the result of a general medical misconception that B. pertussis infection does not frequently occur in the population
Treatment: B.Pertussisisn’t susceptible to penicillins • Erythromycinis DOC adults-250-500mg/6th hr 14 days children-30-60mg/kg/day • Clarithromycin • Azithromycin • Cotrimoxazole • Chloremphenicol Coughsedatives are not useful Corticosteroidsreserved in severe cases, reduceduration of paroxysmal stage. Adrenergicᵦ2 stimulants,reduce severity of paroxysms, more useful in infants.
Prophylaxis: Preventing the spread of disease by isolation isn’tpreferred as max.infectivityis in early stage when ∆ isdifficult. Hence,prophylacticmeasuresmainlyinclude: • immunoprophylaxis Vaccines currentlyused: • DPT/DTwP/Triple antigen vaccine • DTaP • Tdap • Chemoprophylaxis • General prophylaxis
Immunoprophylaxis: 1)DPT/DTwP/Triple antigen vaccine: • Composed of diphteria & tetanustoxoids,killedB.pertussis(smooth phase-1 strain)adsorbed on aluminium phosphate.thiomersol as preservative • Dosingschedule: • 3 Primary doses-at 6,10 & 14 weeks of life • 2 Booster doses-1st booster at 15-18 months -2nd at 5 years • Dose & route:0.5 ml,IM • Site: AL aspect of thigh in infants or deltoid
Last for 1-2 days Treat with analgesics • Side-effects: Minorreactions: • Localized to site-soreness,swelling,redness • Systemic-fever,fussiness,drowsiness,anorexia Moderatereactions: Seen in about 1:100/1000 shots: • Crying non-stop for 3 hrs or more • Fever of 105̊ F or more Lessoften in about 1:1750 shots: • Seizures(convulsions,spasms,staringspells) • Collapse or fainting-childbecomesblue,pale,limp & non-responsive Severereactions:rare Prolongedseizures,↓consciousness,coma,permanentbrain damage & death. !!!DPT vaccine iscontraindicated if moderate to severereactionsoccur.Alsocontraindicatedbelow 6 weeks of life & above 6 yrs
2)DTaP Vaccine: Is an acellular vaccine withpertussis component consisiting of inactivated pertussis toxin, filamentous hemagglutinin, pertactin, or fimbriaealong with diphteria & tetanus toxoids in concentrations similar to DTwP vaccine. • Indicated for children of 6 weeks-6 years of life. • Dosingscheduleis the same.
3)Tdap vaccine: Is an acellular vaccine with concentrations of diphteriatoxoid & pertussis component reduced to 1/10 of DTaP vaccine. • for adolescents between the ages of 10 and 18 years • preservative free (which means that, like most new vaccines, it doesn't contain thimerosal) • A similar Tdap vaccine, Adacel, is being reviewed by the FDA & might be available for people between the ages of 11 and 64, which would be good news for adults who also want protection against pertussis.
Prevention and treatment prophylaxis of secondary cases The CDC has defined a close contact as: • someone having face-to-face exposure within 3 feet of a symptomatic patient • someone who has had direct contact with respiratory, oral, or nasal secretions from a symptomatic patient • someone who has shared the same confined space for more than 1 hour with a symptomatic person. Chemoprophylaxis is given with recommended antibiotics and dosage regimens,identical to those used for treatment of active infection. • should be started in the asympto-matic person within 21 days of cough onset in the index patient. • highly recommended for all children younger than 12 months and women in the third trimester of pregnancy who have been exposed to pertussis
Epidemiology: • Predominantly a pediatricdisease. • Incidence & mortalityhighest in 1st year of life. • Common in femalesthan males at all ages. • Worldwide distribution withmostdeathsoccuring in Africa, Asia,central & latin America. • Occursendemically & epidemically • In recentyears,there’s been resurgence of the disease in USA & easterneuropean countries • Also,there’s an ↑ in number of cases beingreported in Asia.
The Statistics: • According to WHO estimates,around 2.95 lakhpersonsdied of whoopingcough in 2002. • In developingcountries,the case fatality rates range from 4-15% in infants • About 10% of cases & 50% of deathsoccur in children <1yr • In India, there’s been markeddecline in reported cases from 1987-2005 yearcases reported 1987 1.63 lakh 2002 26700 2005 43955