Clinical Epidemiology and Control of Pertussisphs.sbmu.ac.ir/uploads/PERTUSSIS-EPIDEMIO-SLIDES.pdf · 2019. 10. 8. · 2-2. Pertussis Pathogenesis Bordetella pertussis Produces: •

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بسم اهللا الرحمن الرحيمClinical Epidemiology &

Control of Pertussisاپيدميولوژي باليني و كنترل سياه سرفه

Shahid Beheshti Universityof Medical Sciences, 2021

By: Hatami H. MD. MPH

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1) Incubation period2) Natural course 3) Geographical distribution4) Timeline trend5) Age, Gender, Occupation, Social situation6) Predisposing factors7) Susceptibility & Resistance8) Secondary attack rate9) Modes of transmission, period of communicability

Definition and public health importanceEtiologic agent

Clinical Epidemiology of Pertussis

Prevention: Primordial, primary, secondary, tertiary, Puaternary

مقدمه و معرفي بيماري -الف

قوعاپيدميولوژي توصيفي و و -ب

ج ـ پيشگيري و كنترل

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الف ـ مقدمه و معرفي بيماري

بهداشتي اهميت و تعريف ـ1اتيولوژيك عامل ـ 2(Case definition)ـ تعريف مورد 3

ب ـ اپيدميولوژي توصيفي و وقوع(Occurrence)


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1-1. Definition of Pertussisـ تعريف و اهميت بهداشتي 1

• A highly contagious acute bacterial infection caused by the bacilli Bordetella pertussis• Currently worldwide prevalence is diminished due to active immunization• However it remains a public health problem among older children and adults• It continues to be an important respiratory disease afflicting unvaccinated infants and previously vaccinated children and adults (waning immunity).

؟!معضل بهداشتي بهداشتي شيرخواران غيرواكسنيه و كودكان و بالغين واكسنيه

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Bordetella species are small gram-negativecoccobacilli; growth is fastidious.

Filamentous hemagglutinin and fimbriae are two major adhesions.

Pertussis toxin (PT) helps organism evade hostdefenses and causes systemic manifestations; it also acts as an adhesion.

ـ عامل اتيولوژيك2

2-1. Etiologic agent

تزاتجهيزات موثر در بيماريزايي عامل عفون

(Mandell 2020)

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small gram-negative

coccobacilli; growth is fastidious.

2-2. Etiologic agent

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2-3. Pertussis Pathogenesis

Bordetella pertussis Produces: • Toxins namely pertussis toxin, hemagglutinin,

hemolysin, adenylate cyclase toxin, dermonecrotic toxin and tracheal cytotoxin-responsible for clinical features



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2-4. Pertussis PathogenesisRespiratory cilia

Pertussis toxin, causes paralysis of cilia

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2-5. Pertussis Pathogenesis

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تنفسي تاثير توكسين بوردتالپرتوسيس بر سلول هاي مژه اي راه هاي)انيميشن(

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2-7. Environmental resistance

• ??

ـ مقاومت محيطي عامل اتيولوژيك2

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ويژگي هاي مهم عامل عفونتزا

)Infectivity(ـ عفونتزايي 1)Pathogenicity( زايي آسيب ـ 2)Virulence( حدت ـ 3)Antigenicity( آنتي ژني خاصيت ـ 4)Immunogenicity( ايمني زايي خاصيت ـ 5

ـ عامل اتيولوژيك2

تك مخزني: تعداد مخزنانسان به انسان : انتقالانسان : مخزن1313

بيماري مسري 0R آستانه ايمني جامعه

آن ها R)0(بعضي از بيماري هاي عفوني برحسب ميزان بازتوليدي و آستانه وقوع ايمني جامعه و حذف يا ناپديدي آنها

0) / R1–0= (RRt

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(Case definition)تعريف مورد Clinical case definition: • Cough => 14 days

and one or more of the following: • Paroxysmal cough, • Inspiratory whoop, • Posttussive vomiting

سياه سرفهـ تعريف مورد3

Mandell 2020

مورد محتمل؟ مورد قطعي؟

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(Case definition)تعريف مورد Probable Case Cough lasting 2 weeks or longer in the absence of appropriate

laboratory tests and not epidemiologically linked to a laboratory-confirmed case for which there is no other known cause

AND one or more of the following, with no otherknown cause:• Paroxysmal cough of any duration• Cough with inspiratory "whoop"• Cough ending in vomiting or gagging, or associated with apnea

فهسياه سرـ تعريف مورد محتمل3

Public health, (CANADA 2019)

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(Case definition)تعريف مورد Confirmed Case 1. Isolation of Bordetella pertussis from an appropriate clinical

specimen (e.g., nasopharyngeal swabs)OR2. Detection of B. pertussis DNA from an appropriate clinical

specimen (e.g., nasopharyngeal swabs)AND one or more of the following:• cough lasting 2 weeks or longer• paroxysmal cough of any duration• cough with inspiratory "whoop"• cough ending in vomiting or gagging, or associated with apnea

هسياه سرفـ تعريف مورد قطعي3


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(Case definition)تعريف مورد Confirmed Case (2):OR3. Epidemiologic link to a laboratory-confirmed case

رفهسياه سـ تعريف مورد قطعي3


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الف ـ مقدمه و معرفي بيماري

في ب ـ اپيدميولوژي توصي (Occurrence)و وقوع


بهداشتي اهميت و تعريف ـ1اتيولوژيك عوامل يا عامل ـ 2Case) مورد تعريف ـ 3 definition)

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ب ـ اپيدميولوژي توصيفي و (Occurrence)وقوع

(Incubation period) دوره نهفتگي – 1 (Natural course)سير طبيعي – 2 (Geographical distribution)انتشار جغرافيائي – 3(Timeline trend)روند زماني – 4تاثير سن، جنس، شغل و موقعيت اجتماعي – 5 (Predisposing factors)تاثير عوامل مساعد كننده – 6 (Susceptibility & Resistance)حساسيت و مقاومت – 7 (Secondary attack rate)ميزان حمله هاي ثانويه – 8نحوه انتقال و دوره قابليت سرايت – 9

(Mode of transmission & period of communicability)

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1. Incubation period• Usually 10 days, can range from 1-3 weeks.

دوره كمون

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Infection with Bordetella pertussis, is divided in three stages:

o Catarrhal stage: low-grade fever, rhinorrhea, non-purulent conjunctivitis, occasional cough,

Paroxysmal stage: Paroxysms or of coughing, inspiratory whoop

o Convalescent stage: gradually diminishing cough lasting up to 8 weeks.

سير طبيعي

2. Natural course

(Mandell 2020)

22

در سياه سرفه شيرخواران و بزرگساالن Whoopحمالت سرفه هاي قطاري و )فيلم مستند(

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• Secondary pneumonia (1 in 5) and apneic spells (50%; neonates and infant

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Pertussis Complications by Age

0

10

20

30

40

50

60

70

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1. B. parapertussis, adenovirus, mycoplasmapneumonia, and chlamydia trachomatis.

2. Foreign body aspiration, endobronchial tuberculosis and a mass pressing on the airway.

Natural course .2تشخيص افتراقيDifferential diagnosis

تشخيص افتراقي

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Most cases, hospitalizations, and deaths occur in unimmunized infants younger than 6 months of age.

Outbreaks in children with high vaccine rates may be partly due to waning immunity from acellular pertussis vaccine

Young infants (< 6 months of age) have the highest riskof death and this risk is greatest before they are eligible to receive the vaccine or before completion of their primary vaccine series.(CANADA 2019)

Natural course .2پيش آگهيPrognosis

در افراد غيرواكسينه؟ در افراد واكسينه؟؟

(Mandell 2020)

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Protection against pertussis is not lifelong and wanes after 7-20 years of natural infection and approximately 4-12 yearsafter immunization with either whole cell or acellular pertussis vaccine (varies with age).(CANADA 2019)

Natural course .2ايمني پس از بهبوديImmunity

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2. Natural course

ELISAIgG

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ساب كلينيكال(ميزان موارد بدون عالمت(ميزان موارد حاد ميزان موارد مزمنميزان موارد بهبودي خودبخوديسير بعدي بيماري با درمان و بدون درمانميزان مرتاليتيميزان مصونيت بعد از بهبودي

سير طبيعي

2. Natural course

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3. Geographical distribution

• WHO estimated that in 2008, about 16 million cases of pertussis occurred worldwide, 95% of which were in developing countries (WHO)

• 2018 global figures• 151'074 reported cases• 89'000 estimated deaths (2008)• 86% estimated DTP3 coverage•• http://www.who.int/ith/diseases/pertussis/en/

انتشار جغرافيايي

1399تا اول آبان ماه WHOاطالعات موجود در سايت

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به و جهان نقاط تمام در كه است آندميك بيماري هاي جزو•است شايع سن، كم كودكان نزد خصوص،

از ناشي ايمني سطح پوشش كاهش با اخير، سال هاي در• شورهاك از بعضي در ديگر، ناشناخته عوامل و واكسيناسيون،

آن زبرو ميزان بر آمريكا و . . . سوئد ژاپن، انگلستان، نظيراست شده افزوده كودكي، سنين از بعد دوران در بويژه

اين هعلي واكسيناسيون كه افغانستان نظير كشورهايي در • دك،كو و شيرخوار نفر هزاران همواره نمي باشد اجباري بيماري،

.مي باشند بيماري به ابتالء معرض در



32

قطب و بوده افزايش به رو تدريج به ،ايران در بيماريروند• سال در واگير، بيماري هاي مديريت مركز در موجود آمارهاي

افزايش آن از ناشي مرگ مورد 2 و بيماري مورد 142 به 1394است يافته

يرندمي گ قرار درمان، تحت سرپايي طور به بيماران اين اغلب • اردمو ميزان لذا و نمي گردند گزارش و ثبت دقيقي نحو به و

.مي باشد ارقام اين از بيش مراتب، به كشوري



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ـ روند زماني 4پاندمي ها ؟(Pandemics) اپيدمي ها ؟(Epidemics) طغيان ها ؟(Outbreaks) تناوب زماني ؟(Duration) الگوي فصلي ؟(Seasonality)

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4. Timeline trend

Pertussis outbreaks tend to be cyclical in nature with increased disease activity approximately every 3-5 years (c).

Seasonality: Autumn

روند زماني

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اعيـ تاثير سن، جنس ، شغل و موقعيت اجتم 5تاثير سن فخفيو شديدو بدون عالمت و با عالمت، موارد بروزبر ميزان

مرگو ميزان بر عوامل مذكور تاثير جنس؟ شغل و موقعيت اجتماعي

36

اعيـ تاثير سن، جنس ، شغل و موقعيت اجتم 5

According to pre-vaccine data from the USA, approximately 80% of cases occurred in children

37

اعيـ تاثير سن، جنس ، شغل و موقعيت اجتم 5

Case fatality rates (CFR) were and remain highest in infancy (WER 2015).Incidence, morbidity and mortality

are higher in females than males.(Cont. 2008)

تاثير سن و جنس؟

38

اعيـ تاثير سن، جنس ، شغل و موقعيت اجتم 5 A shift in the age distribution towards older

age groups has been reported in recent years in some high income countries,

In particular where aP vaccines have replaced wP vaccines for primary vaccination series.

انحراف سنّي به سنين باالتر در كشورھاي با وضعيت اقتصادي خوب؟

40

ـ تاثير عوامل مساعد كننده 6

عوامل فرهنگي و عقيدتير ايمني، زمينه هايي نظير ضعف ايمني، ابتالء به بيماريهاي سركوبگ

مصرف داروهاي مضعف سيستم ايمنياسترس هاي مختلففقر و بي خانماني

عوامل تماسي عوامل ميزباني عوامل محيطي

عوامل تماسي عوامل ميزباني عوامل محيطي

41

6. Predisposing factors

In non-immunized populations, especially those with underlying malnutrition and multiple enteric and respiratory infections, pertussis is among the most lethal diseases of infants and young children.

عوامل مساعد كننده؟

42

يـ حساسيت و مقاومت در مقابل بيمار 7مقاومت طبيعيمصونيت اكتسابي بعد از ابتالءمصونيت اكتسابي بعد از واكسيناسيون

43

7. Susceptibility & Resistance

• Non-immunized or partially immunized individuals are susceptible to pertussis.

• Previously immunized adolescents and adults (due to waning immunity) may also be susceptible.

• Infection does not induce long term immunity.

• Although antibodies cross the placenta, transplacental immunity in infants has not been demonstrated.(cont.)

حساسيت و مقاومت

ايمني انفعالي در دوران شيرخوارگي؟

44

8. Secondary attack rate

• Secondary attack rate up to 90%• In its early catarrhal stage, is highly

contagious, with a secondary attack rate of up to 90% among non-immune household contacts (WER 2015)

ميزان حمالت ثانويه

45

9-1. Modes of transmission

• Transmission occurs by direct contact with discharges from respiratory secretions of infected persons via droplets.

راه هاي انتقال و دوره قابليت سرايت

46

9-2. period of communicability• Highly communicable in the early catarrhal

stage and beginning of the paroxysmal stage (first 2 weeks) and then communicability gradually decreases and becomes negligible in about 3 weeks.

• No longer communicable after 5 days of effective treatment (CANADA 2019)

دوره قابليت سرايت

دوره قابليت سرايت؛ با درمان و بدون درمان؟

47

9-3. Reservoir

Humans are the only known reservoir Adolescents and adults are often the source

for infants.

مخزن بوردتال پرتوسيس

50

يالف ـ مقدمه و معرفي بيمار

في ب ـ اپيدميولوژي توصي) Occurrence(و وقوع

ج ـ پيشگيري و كنترل)Primordial( مقدماتي ـ 0)Primary( اول سطح ـ1 )Secondary( دوم سطح ـ 2 )Tertiary( سوم سطح ـ 3)Quaternary( چهارم سطح ـ 4

رفهسياه سج ـ پيشگيري و كنترل

51

رفهسياه سج ـ پيشگيري و كنترل

• Primordial Prevention: “…minimize hazards to health”• Primary Prevention:

Prevention of disease in “well” individuals• Reduce the incidence of disease• Secondary Prevention:

Identification and intervention in early stages of disease (usually at asymptomatic stage)

May improve effectiveness of intervention• Reduce the prevalence of disease• Tertiary Prevention:

Prevention of further deterioration, reduction in complications• Reduce the impact of complications • Quaternary Prevention

52

1. Primary prevention

• Educate population• Immunoprophylaxis

پيشگيري و كنترل

53

Vaccination• All children should be immunized beginning at

2 months of age. • A primary series consisting of:

• 3 doses at 2, 4, and 6 months of age

واكسيناسيون

54

برنامه ايمنسازي كودكان در جمهوري اسالمي ايران

55

نواكسيناسيوتاخيري

برنامه ايمنسازي كودكان در جمهوري اسالمي ايرانماهگي 3-12مراجعه

56

برنامه ايمنسازي كودكان در جمهوري اسالمي ايرانسالگي 1-6مراجعه

57

Vaccination for Pertussis

(Mandell 2020)

58

• Immunization is the single most effectivemeans of preventing pertussis.

• Pertussis immunization schedule in IRAN• for children and adolescents: DTaP 2, 4, 6, and

18 months, with booster at 6 years; • for preadolescents/adolescents Tdap.

Pertussise immunization

واكسيناسيون عمومي

Mandell 2020&IRAN

59

• All health care workers with patient contact should be given a single dose of Tdap if they have not been vaccinated as an adult, irrespective of when they received the last dose of tetanus toxoid.

Pertussise immunizationدر كاركنان بهداشتي تماس يافته واكسيناسيون

Mandell 2020

60

سياه سرفه مقايسه اجزاء واكسن سلولي كامل و فاقد سلول

61

Adverse reactionsWhole-Cell Vaccines

1. The problem with whole-cell pertussis vaccines is their reactogenicity.

2. It is known that DTP vaccine causes significantly more local reactions (redness, swelling, and pain) and systemic reactions, such as drowsiness, vomiting, and persistent crying, than acellular pertussis vaccines and DT alone.

3. More serious adverse events, such as convulsions and hypotonic and hyporesponsive episodes (HHE), are much rarer occurrences, especially after the introduction of acellular vaccines.

عوارض واكسن سلولي و فاقد سلول

عوارض واكسن؟

(Mandell 2020)

62

1. In 1991, the U.S. Institute of Medicine reviewed all the literature and concluded that there was no evidence to support an association between pertussis immunization and permanent neurologic damage.

واكسيناسيون

Mandell 2020

Adverse reactionsWhole-Cell Vaccines

63

Contraindications and Precautions:

1. The only true contraindication to immunization with aP or wP is an anaphylactic reaction to a previous dose or to any constituent of the vaccine.

2. In young infants with suspected evolving and progressive neurological disease, immunization may be delayed for some months to permit diagnosis, in order to avoid possible confusion about the cause of symptoms.

موارد ممنوعيت مصرف واكسن/واكسيناسيون

Cont. 2008

6464

Vaccination coverage

67

• Prophylaxis can be considered for close contacts exposed within 21 days of onset of cough in the index case.

• Adults and adolescents are given erythromycin 500 mg four times daily for 7 to 14 days, azithromycin 500 mg the first day and 250 mg daily for 4 additional days, or clarithromycin 500 mg twice daily for 7 days.

Post-exposure Prophylaxis

پروفيالكسي بعد از تماس

Mandell 2020

6868

افراد آسيب پذيردر تماس هاي خانوادگي: الف

شيرخواران كمتر از يك ساله _ 1خانم هاي باردار در سه ماهه سوم حاملگي _ 2در ساير تماس ها : ب

مشروط بر تماس چهره به چهره و يا 2و 1همان موارد دود استنشاق از هواي مشترك در يك مكان سربسته و مح

...)كالس (


پروفيالكسي بعد از تماس


69

• Respiratory isolation for known cases. Suspected cases should be removed from the presence of young children and infants, especially non-immunized infants, until the patients have received at least 5 daysof antibiotics.

• Suspected cases who do not receive antibiotics should be isolated for 3 weeks after onset of paroxysmal cough or until the end of cough, whichever comes first. (cont. 2008)

Isolation of patients:پروفيالكسي بعد از تماس

(Mandell 2020)

نوع ايزوالسيون

مدت در افراد تحت درمان

مدت در افراد بدون درمان

70


Mandell 2020

71


Mandell 2020

72

2. Secondary preventionEarly detection and promptly treatment

Diagnosis1. Made by culture from nasopharyngeal swabs

or aspirates;2. Newer PCR assays are more sensitive for

detection of B. pertussis and are the procedure of choice.

3. • Antibodies to B. pertussis PT can be used for diagnosis.

4. Direct fluorescent antibody is available but not recommended.

پيشگيري سطح دوم

Mandell 2020

73

كشت

PCR

تظاهرات بالينيسرولوژي

ELISA IgG

حساسيت تشخيصي آزمون هاي مختلفدر مراحل سه گانه سياه سرفه

Ref. Laboratory Diagnosis of Pertussis. https://cmr.asm.org/content/cmr/28/4/1005.full.pdf

74

• Pertussis toxin is the most common antigen used for B. pertussis serologic testing

• The advantage of serology is that by the time the patient presents with typical symptoms of pertussis, the antibody response is usually present.

• In contrast, NP cultures are usually positive only early in the course of the disease.

• Most laboratories use an ELISA to detect antibodies to B. pertussis.

تشخيص سياه سرفه با بررسي آنتي باديهاي ضد توكسين پرتوسيس

Mandell 2020

محاسن بررسي آنتي بادي؟

75

• Unfortunately, young infants may not produce an antibody response to PT.

• Although there are ELISAs to detect IgG, IgA, and IgM to B. pertussis, IgG assays are the most frequently used as a diagnostic test and are the best standardized and most widely available.

• IgG rises typically 2 to 3 weeks after infection or primary immunization and 1 week after booster

• immunization.

تشخيص سياه سرفه با بررسي آنتي باديهاي ضد توكسين پرتوسيس

Mandell 2020

محدوديتهاي بررسي آنتي بادي؟

76

2. Secondary prevention پيشگيري سطح دوم

Mandell 2020

77

2. Secondary prevention

• Treatment: • Erythromycin, 40 to 50 mg/kg/day in four divided doses, is

recommended for children (maximum 2 g/day) or clarithromycin, 15 mg/kg/day in two divided doses (maximum 1g/day) for 7 to 14 days.

• Azithromycin is recommended for infants younger than 1 month of age.

• Five days of azithromycin is probably effective for treatment or prophylaxis in adults (500 mg first day, then 250 mg daily) and is better tolerated and has fewer serious drug interactions than erythromycin, 500 mg four times daily for 14 days.

پيشگيري سطح دوم

78

Pertussis3. Tertiary prevention•

پيشگيري سطح سوم

79

اجتناب از انجام اقدامات و تشخيصي ـ درماني غيرالزمتحميل هزينه هاي ذيربط

پيشگيري سطح چهارم

4. Quaternary prevention

80

PertussisReferences:• Mandel 2020• Harrison 2018• Public Health Canada, 2019.• World Health Organization, Factsheet, Immunization Coverage, 15

July 2020.https://www.who.int/news-room/fact-sheets/detail/immunization-coverage• World Health Organization, Site, 2020,Pertussis and Pertussis

Toxoid, National Immunization CDC. • Ehsanur Reza, MBBS, FCPS, Assistant Professor Surgery Unit III

MMCH • Sarika Gupta, Diphtheria, Pertussis, Pertussis.

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كآدرس اساليدها و كتب الكتروني :در سايت هاي اينترنتي

https://sites.google.com/site/drhatamilibrary 🌴 در سايت گوگلhttps://sites.google.com/site/drhatamilibrary7/mph_class/clinical_epidemio_inf-htm

https://sapp.ir/drhatamilibrary در پيام رسان سروش��

https://eitaa.com/drhatamilibraryدر پيام رسان ايتا ��

http://www.elib.hbi.ir/persian/LIBRARY.htm مسدود گرديده است1393از سال

اي اپيدميولوژي باليني و كنترل بيماري ه)سياه سرفه( عفوني

82

اي اپيدميولوژي باليني و كنترل بيماري ه)سياه سرفه( عفوني

يوتيوب درسرفه سياه كنترل و باليني اپيدميولوژي درس آموزشي فيلم هايبخش اول ويدئوي درس اپيدميولوژي باليني و كنترل سياه سرفه

https://youtu.be/2fTkupJ2Jsk بخش دوم ويدئوي درس اپيدميولوژي باليني و كنترل سياه سرفه

https://youtu.be/2GZyliGt8fc

استفاده نماييد VPNدر صورت عدم نمايش فيلم هاي آموزشي در يوتيوب ، لطفا از

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Clinical Epidemiology and Control of Pertussisphs.sbmu.ac.ir/uploads/PERTUSSIS-EPIDEMIO-SLIDES.pdf · 2019. 10. 8. · 2-2. Pertussis Pathogenesis Bordetella pertussis Produces: •