Epidemiology and Burden of Pertussis: Focus on Adolescent and Adult

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1 Epidemiology and Burden of Pertussis: Focus on Adolescent and Adult Terapong Tantawichien Division of Infectious Diseases Department of Medicine, Chulalongkorn University And Queen Saovabha Memorial Institute

2 Pertussis Vaccine Whole-cell pertusssis vaccine (DPT) WC in adults adverse reactions Acellular pertussis vaccines (DTaP, ap,tdap) (components: PT; pertussis toxin, FHA; filamentous hemagglutinin, PRN; pertactin, FIM; fimbrial agglutinogens) Mild adverse reactions ( erythema,induration,fever,rash ) High immunogenicity in adults ( booster ) Decline in level of antibody after vaccination Indications for Vaccine: - Immunization of infants and children/dtp,dtap,tdap - Immunization of adolescent and adults: Tdap/replace dt - Use of vaccine in outbreaks

3 What are the Recommendations for Pertussis Vaccination? Pediatric Immunization in Thailand ( 2009) Public sectors Private sectors Birth BCG, HBV BCG, HBV (1 M HBV for HBsAg+ mother only) 2, 4 M DTP-HB, OPV DTaP-IPV-Hib+HBV, PCV-7, Rota 6 M DTP-HB, OPV DTaP-IPV-Hib-HBV, PCV-7, Influenza (2 doses 4 wk apart) 9 M Measles MMR M JE (MB)x3 Live JEx 2 VZV, HAVx2, PCV-7 18 M DTP(97.5%), OPV DTaP-IPV-Hib 4-6 Y DTP(79.4%), OPV, MMR MMR, VZV, Tdap-IPV 9 Y - HPVx3 6M 5Y - Influenza yearly 9-15 Y Td (no data) q 10 yrs Td q 10 yrs ( Tdap replace one dose of Td)

4 Are there any beyond Childhood in Thailand? 1 booster dose of Tdap for adolescent ( 9-12 yrs )-Recommended by ID Society, experts Tdap replace one dose of Td in adult ( low compliance of decennial Td vaccination ) 1 booster dose of Tdap for health-care workers ( optional vaccine )

5 Pertussis in Adolescent and Adult Factors determining the prior use of vaccine : Importance of the disease Burden of pertussis in adolescent/adult Morbidity/mortality of pertussis in adolescent/adult Targeting of program Adult-vaccine program and access to targeted population Cost of vaccination( Cost/effectiveness ) Acceptance ( awareness is low ) ; both in medical profession/population )

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9 The Advisory Committee on Immunization Practices (ACIP) recommends that: MMWR Dec 2006,2008 1) Adults aged years should receive a single dose of Tdap to replace Td ( not previously received Tdap) 2) Intervals shorter than 10 years since the last Td may be used for booster against pertussis 3) Adults who have or who anticipate having close contact with an infant aged <12 months should receive a single dose of Tdap Women should receive a dose of Tdap in the immediate postpartum period 4) Health-care personnel who have direct patient contact should receive a single dose of Tdap as soon as feasible if they have not previously received Tdap.

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15 Percentage of total cases (age-specific) Age 0 Age 1-2 Age 3-9 Age Age Age >45 year Changes in age distribution of pertussis cases in Japan

16 Summary of studies that estimated the proportion of prolonged cough illness caused by B. pertussis in adolescents and adults Ambulatory patients ( Canada ) Ambulatory patients ( USA ) Ambulatory patients ( during outbreak ) Adult patient at ER (USA) Household contact (Germany) University students (USA) University student (USA) US marine corp trainee Pulmonary clinic (Australia) Pulmonary clinic (Denmark) Most of them were diagnosed by serologic method % 12.4% 26% 21% 26% 26% 9%(36%mixed inf ) 17% 25.7% 16.4%(5.5%confirm)

17 What is the Burden of Pertussis in Your Country?

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19 Fig 3 Reported Cases of Pertussis per 100,000 Population, by Age-group, Thailand, Rate per 100,000 P op

20 ป พ.ศ ม รายงานการสอบสวนการระบาดจากจ งหว ดน าน เหต การณ แรกระหว างว นท 28 ก มภาพ นธ 9 ม นาคม พบผ ป วยจ านวน 3 ราย อาย 4 เด อน 1 ราย และ 4 ป 2 ราย เข าร บการร กษาเป นผ ป วยใน 2 ราย ในจ านวนน ม 1 ราย ได ร บว คซ นไม ครบตามเกณฑ ผลการตรวจท กราย PCR เหต การณ ท สอง ม ผ ป วยจ านวน 57 ราย ว นท 20 ก มภาพ นธ รายส ดท ายว นท 6 เมษายน 2549 ในกล มอาย 5-9 ป ร อยละ อาย ป ร อยละ และอาย ป ร อยละ ผลการตรวจ PCR จากต วอย าง Nasopharyngeal swab ในผ ป วยจ านวน 22 ต วอย าง พบ เช อ Bordetella pertussis จ านวน 2 ต วอย าง ม ประว ต ได ร บว คซ น 18 ราย (ร อยละ 31.58)

21 Epidemiological studies suggest that pertussis Is common and frequently unrecognized infection in adolescents and adults The incidence of reported pertussis has increased dramatically Highest incidence of reported cases is among infant Highest morbidity and mortality in infant < 1 year The most rapid increasing in incidence is among adolescents/adults 12-32% of illnesses with prolonged cough are due to pertussis Incidence in young adolescents are higher than for adults

22 PERTUSSIS IN ADOLESCENTS AND ADULTS REMAINS UNDERRECOGNIZED AND UNDERDIAGNOSED

23 Increasing of reported pertussis in adults : -Still underestimated? 1-2 cases/1000 adults/year -Signs/symptoms of illness - Similar other respiratory diseases (cough with vomiting, prolonged cough, whooping cough,paroxysmal cough ) -Diagnosis tools? Culture ( low sensitivity 10% ), PCR ( 20% ) serologic diagnosis ( no standardization ) diagnosis tests are not considered by doctors -Asymtomatic/ mild disease

24 Pertussis ( Communicable Diseases ) : Case Definition for Surveillance Suspected case : Clinical case definition Probable case : Clinical case plus outbreak Confirmed case : Clinical case plus laboratory diagnosis Clinical case definition Cough illness lasting > 2 weeks with one of the following: Paroxysms of coughing Inspiratory whooping Post-tussis vomiting Laboratory criteria for diagnosis Isolation of Bordetella pertussis from clinical specimen Positive PCR for B. pertussis Serology Pertussis is still present esp. in adolescents and adults, but hard to make diagnosis

25 Clinical Symptoms in Adult Patients Diagnosed with Pertussis Paroxysmal cough 70-94% Whoops 8-38% Pertussis emesis 17-42% Awakened by cough 52-88% Sputum production 66-79% Fever (history) 26-38% Preceeding URI 44-58% Pharyngitis 3 1% Sweating attacks 14%

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27 Rothstien E;Pediatr Infect Dis J 2005;24: S44 S47)

28 Summary of studies that estimated the proportion of prolonged cough illness caused by B. pertussis in adolescents and adults Ambulatory patients ( Canada ) Ambulatory patients ( USA ) Ambulatory patients ( during outbreak ) Adult patient at ER (USA) Household contact (Germany) University students (USA) University student (USA) US marine corp trainee Pulmonary clinic (Australia) Pulmonary clinic (Denmark) Most of them were diagnosed by serologic method % 12.4% 26% 21% 26% 26% 9%(36%mixed inf ) 17% 25.7% 16.4%(5.5%confirm)

29 Incidence trend of reported pertussis cases per million in Taiwan during Between 1993 and 2004, a total of 2452 cases of pertussis were reported by hospitals located in different areas of Taiwan to the Center for Disease Control, Taiwan Lin CH; Journal of Medical Microbiology (2007), 56,

30 Incidence trends of reported pertussis cases per million by age group in Taiwan during The upward trend in incidence was more significant for infants and adolescents (P<0.01), and the highest slope for incidence increase was found in adolescents aged years. Lin CH; Journal of Medical Microbiology (2007), 56,

31 Detection of B. pertussis by PCR or serology ( 7.2% in Patients with prolonged cough > 1 week( Taiwan ) Lab test 1-4 yrs 5-9 yrs yrs > 20yrs total n=15 n=34 n=25 n=37 n=111 PCR (0.9%) n=6 n=5 n=9 n=13 n=33 IgG to PT IgA to PT >1 test (21%) Ho JJ; J Microbial Immunol Infect 2006

32 High Incidence of Pertussis among Hajj Pilgrims Annelies Wilder-Smith, Clin Infect Dis of 358 pilgrims (1.4%; 95% CI, 0.5% 3.2%) had a >4- fold increase in the level of IgG, and all 5 reported developing a prolonged cough during the Hajj, thus meeting the criteria we defined for acquisition of pertussis. None of these 5 had symptoms of cough before their departure for or after their return from the Hajj. Of the 40 pilgrims who had no pre-hajj immunity to pertussis, 3 (7.5%; 95% CI, 1.6% 20.4%) acquired pertussis. Among 204 pilgrims with prolonged cough, pertussis was present in 2.5% (5 pilgrims).

33 Clin Infect Dis 2006

34 C H Wirsing von König; Lancet Infect Dis 2002

35 Seroprevalence of IgG antibodies against Bordetella pertussis in healthy individuals aged 4 24 years in Turkey. M. Cevik ; Clin Microbiol Infect 2008

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37 Age Population (n) Mean + SD of % of persons who had (years) pertussis antibody* history of pertussis (ug/ml) vaccination 0-4 Ill children (50) >4-15 School children (250) >15-30 Blood donors (300) >30-50 Blood donors (350) >50-60 Blood donors (400) >50 Population at Rumkloa, Bangkok (817) Pertussis antibody in Thai population of Bangkok, Thailand (1998)

38 ug/ml VAC 70% VAC 72% VAC 45% VAC 24% VAC 14% 0-4 *>4-15 **>15-30 **>30-50 **>50-60 ***>50 Antipertussis antibody in Thai population of Bangkok *school children ** blood donors *** population in Romkloa, Bangkok

39 Pertussis in Adolescent and Adult Factors determining the prior use of vaccine : Importance of the disease Burden of pertussis in adolescent/adult Morbidity/mortality of pertussis in adolescent/adult Targeting of program Adult-vaccine program and access to targeted population Cost of vaccination( Cost/effectiveness ) Acceptance ( awareness is low ) ; both in medical profession/population )

40 Clinical Significance of Pertussis in Adults Mortality: essentially nil Morbidity Prolonged cough syndrome Hospitalization, absenteeism, cost of therapy, complications ( cough with vomiting/choking, weight loss, rib fracture, pneumonia,seizure, encephalopathy ) Other potential morbidity (possible role acute infection in COPD)

41 Pertussis-Related Hospitalizations, Complications and Deaths, by Age Group: USA Age Pts/Hospitalization Pneumonia Seizure Encephalopathy Deaths < 6 mos 7203/63.1% mos 1073/28.1% yrs 3137/10.3% yrs 2756/3.1% yrs 8273/2.1% >20 yrs 5749/3.5% Total 28187/20% (0.2%) MMWR 2002

42 83% of adolescents missed a mean of 5.5 days from school (range, days), and 61% of adults missed a mean of 9.8 days from work (range, days) because of pertussis. Societal Costs and Morbidity of Pertussis in Adolescents and Adults Lee GM: CID 2004 In the analysis of medical costs, 1679 adolescents and 936 adults were found to have mean costs of $242 and $323, respectively. In interviews with 314 adolescents and 203 adults, adults had significantly higher nonmedical costs ($447) than those of adolescents ($155).

43 Transmission of Pertussis Frequency of transmission in household contacts 26% primary cases of > 30 years ( USA 1996 ) 53% primary cases of > 13 years ( Germany 1994 ) Adults are the primary source of infants : Parent, child-care persons, post-partum women, grandmother-father Adolescents ( in school )

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45 Greeff SC; Clin Infect Dis 2010

46 The 100-day cough : The time to prevention has arrived Marchant CD; Clin Infect Dis 2004 ( Editorial comment )

47 Goals of Pertussis Prevention in Adults Primary goal: Reduce transmission to infants Secondary goal: Reduce morbidity in older children/young adults Reduce morbidity in all adults Develop herd immunity to reduce transmission

48 Control options of pertussis immunization Kevin Forsyth : Clin Infect Dis 2007

49 What are the Gaps that will need to be addressed to support pertussis prevention in adult? No epidemiology data of pertussis in adolescent and adult : Clinical studies Lack of Laboratory diagnosis for pertussis : PCR and serodiagnosis Lack of awareness and diagnosis of adult pertussis : Education Poor compliance of adolescent and adult vaccination: Awareness of booster vaccination in adolescent and adult ( Tdap, HPV,..) High cost of vaccination : Free vaccination ( EPI )

50 Which is the Likely Strategy for Adolescent/Adult Vaccination in Thailand? Routine booster dose for preteenagers and teenagers. (EPI with Tdap or optional vaccine) Established prevalence and burden of pertussis in Thailand Increased knowledge of adolescent and adult immunization in Thai population/physician Universal decennial Td program for adult (EPI) and free/optional Tdap vaccine for adult Routine Tdap vaccination for high-risk health-care workers (free) Tdap vaccination at immediate post-partum period ( replace Td )

51 Pertussis in Adolescent and Adult Factors determining the prior use of vaccine : Importance of the disease Burden of pertussis in adolescent/adult Morbidity/mortality of pertussis in adolescent/adult Targeting of program Adult-vaccine program and access to targeted population Cost of vaccination( Cost/effectiveness ) Acceptance ( awareness is low ) ; both in medical profession/population )

52 Thank you Thank you