OB/GYNS as VACCINATORS

Transcription

1 OB/GYNS as VACCINATORS It s a New Era Linda O. Eckert, MD Associate Professor Department of Obstetrics & Gynecology University of Washington

2 Disclosure I have no conflicts of interest to report

3 Objectives Vaccine Update Influenza vaccine review/update Pertussis New recommendations Meningococcus HPV vaccine Obstacles to overcome/ Routines to put into place

4 Influenza As providers of health care for women, many of whom are healthy, why should we care?

5 Influenza Virus Type of nuclear material Hemagglutinin Neuraminidase A/Fujian/411/2002 (H3N2) Virus type Geographic origin Strain number Year of isolation Virus subtype

6 Antigenic Changes Influenza Possible Change Subtype Cause Result Antigenic Minor Same Point Epidemic DRIFT mutations in gene Antigenic Major New Exchange Pandemic SHIFT of gene segments

7 Clinical Description/Diagnosis Influenza Incubation period 1 1 to 4 days Group Adults Children Severely immunocompromised Infectious Period From day before illness onset to +5 days after 10 days (can shed virus several days before onset) Can shed virus for months Likely transmission paths 2 Respiratory droplets from coughing/sneezing Not washing hands after contact with infected person 1. CDC. MMWR. 2005;54(RR-08): American Academy of Pediatrics. Red Book. 2003,

8 Abrupt Onset Fever Myalgia Headache Malaise Signs and Symptoms Influenza Differential Diagnosis Can be difficult based on symptoms alone, unless influenza already present in community Children and elderly can have different presentations Can last up through 7 days CDC. MMWR 2005;54(RR-8):2 3. Nonproductive cough Sore throat Rhinitis

9 Complications Influenza Most vulnerable patients 1 Age 65 yrs and children 2 yrs of age Underlying chronic conditions at any age Heart or lung disease Diabetes Compromised immune system Secondary complications 2,3 1 influenza viral pneumonia or 2 bacterial pneumonia Exacerbation of underlying cardiac or pulmonary disease 2 or co-infection with other viral/bacterial pathogens 1. CDC. MMWR 2005;54(RR-08):3, HHS. Available at: Accessed July 6, American Academy of Pediatrics. Red Book 2003;

10 Influenza in the United States Annually >200,000 Hospitalizations 36,000 Deaths

11 Costs Influenza Direct Medical Costs: Up to $3 billion/year 1 (hospitalizations, office visits, medications) Lost Work Days: 2.8 to 3.4 per episode Absenteeism: 75 million days in 1995 Presenteeism: 0.7 days per episode (at work but less productive) Total direct and indirect costs (work days, school days lost) $12 billion or greater for severe epidemic 1,2 1. Nichol KL. Arch Intern Med 2001;161: Patriarca PA, Strikas RA. N Engl J Med 1995;333:

12 Target Groups for Vaccination Influenza People at high risk for complications, hospitalizations, or death from influenza: 1 65 yrs Children 6 mos up to 18 yrs of age 2 Nursing home residents Persons with chronic pulmonary or cardiovascular disorders Persons with chronic metabolic diseases Those with conditions that can compromise respiration Children 6 mos to 18 yrs on long-term aspirin Women who will be pregnant during the influenza season 1. CDC. MMWR 2005;54(RR-08): CDC

13 Inactivated Influenza Vaccines Available in Vaccine Package Dose Age Thimerosal Fluzone Multi-dose vial* Age-dependent 6 mos Yes (Sanofi Pasteur) Single-dose syringe* 0.25 ml 6 35 mos No Single-dose 0.5 ml 36 mos No syringe* Single-dose vial* 0.5 ml 36 mos No Fluvirin Multi-dose vial 0.5 ml 4 yrs Yes (Novartis) Fluarix Single-dose 0.5 ml 18 yrs Trace (GSK) syringe FluLaval Multi-dose vial 0.5 ml 18 yrs Yes (GSK) *vaccines approved for children younger than 4 years

14 Immunization for Kids Influenza New Recommendations Annual flu vaccination for all children 6 mos through 18 yrs VFC coverage started 7/1/08 Children 6 months to 8 years need two doses, separated by 4 or more weeks MMWR July 2008; RR-57:1 60.

15 Complications and Concerns Influenza Use of LAIV with restrictions For anyone with asthma and children 2-4 with recurrent wheezing due to potential for wheezing post-immunization For anyone who is at risk for wild type influenza complications (medical conditions) Major AE include runny nose, fever >100 F and sore throat in adults for LAIV, and sore arm, irritability, fever for TIV Contraindications Hypersensitivity to eggs, gentamycin, gelatin, previous life threatening reactions to flu vaccine

16 Why Emphasize Kids? Influenza Infants have higher morbidity and mortality with influenza Children act as major vectors for transmission of influenza Use of flu vaccine does impact community spread Children often have habits that facilitate transmission Sharing toys, sneezing on others, etc.

17 Role of OB/GYNs Influenza Women who are pregnant or in the childbearing years often have other children Kids need parents to take them in for immunizations Parents need to understand rationale for vaccinating Parents need to understand risks of disease far outweigh risks of vaccine OB/GYNs can be important sources of information to get kids immunized

18

19 Why are pregnant women considered high-risk?

20 Increased Risk of Exposure to Influenza Pregnant Women Women of childbearing age have exposure to young children, and may have an rate of exposure compared to general adult population Overall risk of exposure high* annually influenza infects ~10% of adults Up to ~30% of children *Neuzil, Griffin. Inf Dis Clin N Am 2001;15:123.

21 Historical Reports Influenza Pandemics 1918: Mortality associated with infection during pregnancy ~51%, with highest rates in later stages of pregnancy (Harris. JAMA 1919;14:978) 1957: 50% of women of childbearing age who died of influenza were pregnant 10% of all influenza deaths that season were in pregnant women, most in latter half of pregnancy Greenberg et al. AJOG 1958;76:897) (Freeman, Barno. AJOG 1959;78:1172; Case reports of complications since then, many in later stages of pregnancy (Neuzil et al. Inf Dis Clin N Am 2001;15:123)

22 Incidence Rates Acute Cardiopulmonary Events Low-Risk Women, Ages 15 44, Based on Pregnancy Status Not N o n - Pregnant p r e g n a n t wks Postpartum 1 4 t o 2 6 P o s t p a r t u m Non-influenza Peri-influenza Influenza N o n-influenza P eri-influenza Influenza Neuzil et al, Am J Epi 1998;148:1094.

23 Effect of Pregnancy on Influenza-Related Hospitalizations Cardiopulmonary Hospitalizations per 10, Not pregnant 1st trimester 2nd trimester 3rd trimester Postpartum Non-flu Peri-flu Flu Neuzil, et al. NEJM 1996.

24 Stage of Pregnancy Modifies Outpatient Influenza-like Illness (N = 8,323 Healthy Pregnant/Postpartum Women, ) Trimester Risk of Developing Illness with Exposure OR (95% CI) First 1.12 ( ) Second 1.30 ( ) Third 1.84 ( ) Postpartum 2.28 ( ) Lindsay. Am J Epidemiol 2006;163:

25 Severe 2009 H1N1 Influenza in Pregnant and Postpartum Women in California April 23-August 11, 2009 reproductive aged women N=94 preg women, 8 postpartum, 137 non-pregnant reproductive age with H1N1 Later treatment (>2 days from sx onset) in pregnant women was associated with ICU admission or death; RR= pregnant women, 4 post partum women (22 of 102, 22%), required ICU stay. 8 (8%) died 2009 H1N1 influenza-specific maternal mortality ratio was 4.3 (deaths per 100,000) Louie et al, NEJM 2010; 362:27-35.

26 H1N Influenza Virus Infection During Pregnancy in the USA CDC collected reports from 13 states of H1N1 in pregnant women April 15-May 18, cases in pregnant women from 13 states 11 (32%) admitted to hospital Admission rate in pregnant women 0.32 (CI ) per 100,000 vs (CI ) in the general population 6 deaths in pregnant women between April 15 and June 16, 2009 promptly treat pregnant women with anti-influenza drugs Jamieson et al, Lancet 2009; 374:451-58

27 Vaccinating Pregnant Women ACOG Committee Opinion Influenza vaccination is an essential element of prenatal care women who will be pregnant in the influenza season (October through mid-may) should be vaccinated may be used in all 3 trimesters. ACOG Committee Opinion #305, November 2004

28 However pregnant women are frequently not being vaccinated! Only 13% of pregnant women received an influenza vaccination in 2003 This led to 2004 National Survey by ACOG/CDC Of those obstetricians surveyed: 52% recommended influenza vaccine in 1 st 95% recommended it in 2 nd Only 36% offered it in their offices MMWR 2005;54(42):

29 H1N1Vaccination coverage in US October December % coverage among pregnant women of the 2009 H1N1vaccine Typically, 15-25% coverage in pregnant women for seasonal flu vaccine To improve influenza vaccination coverage among pregnant women, efforts should continue to urge obstetricians and other health-care providers to provide influenza vaccine to pregnant women By end of December, only 22% of health care workers reported having been vaccinated MMWR Jan 2010, 59(02):44-48

30 Is 38% coverage in pregnant women good enough? ACOG has worked hard to get the word out to treat early and to vaccinate From August 27, 2009 to Dec 14, 2009, ACOG College President issued 6 updates ACOG website has 13 links on H1N1 including CDC recommendations, safety updates, and treatment information What will it take to increase coverage? [2009 H1N1 Influenza Virus]

31 Vaccinating pregnant/postpartum women is efficient Based on the study of 8,323 healthy pregnant and postpartum women from : Need to vaccinate pregnant or postpartum women with an 80% effective vaccine to prevent one episode of influenza-like illness Lindsay, Am J Epidemiol 2006;163:

32 Influenza in Infants Transplacentally-acquired Influenza Antibody Infants are protected from symptomatic influenza A virus infection by transplacentally acquired antibody (Puck et al, J Infect Dis 1980;142:844 9) Passive maternal antibody to influenza A/H1N1 delays onset and severity of influenza disease in 39 mother-infant pairs (Reuman et al, PIDJ 1987;6: )

33 Mothers and Infants Effectiveness of Maternal Influenza Immunization Prospective, randomized trial in Bangladesh 340 mothers receive influenza vaccine or pneumococcal vaccine (control) Mothers and infants followed 16 months Endpoints: Laboratory-confirmed influenza in infants Febrile respiratory illness in mother and in infant Zaman et al. NEJM Oct 9, 2008;359(15):

34 Lab-Proven Influenza in Infants Whose Mothers Had Influenza Vaccine vs. Controls Zaman et al. NEJM Oct 9, 2008;359(15):

35 Episodes Respiratory Illness with Fever in Infants Whose Mothers Had Influenza Vaccine vs. Controls Zaman et al. NEJM Oct 9, 2008;359(15):

36 Effectiveness Maternal Influenza Immunization MOTHERS Person-months 1,076 1,089 Episodes Clinical Risk Ctrl Flu Vac Effectiveness Difference Group Group (95% CI) (95% CI) Resp Illness/fever Any fever ( ) ( )* Temp >38 C ( ) -7.3 ( )* Diarrheal disease ( ) -5.9 ( ) Clinic visit ( ) -3.2 ( ) *p<0.05 Zaman et al. NEJM Oct 9, 2008;359(15):

37 Effectiveness Maternal Influenza Immunization INFANTS Person-months Episodes Clinical Risk Ctrl Flu Vac Effectiveness Difference Group Group (95% CI) (95% CI) Resp Illness/fever Any fever ( ) ( )* Temp >38 C ( ) ( ) Diarrheal disease ( ) -1.6 ( ) Clinic visit ( ) ( )* Influenza test ordered ( ) ( )* Influenza test ( ) -6.4 ( )* *p<0.05 Zaman et al. NEJM Oct 9, 2008;359(15):

38 What Is the Effect of Influenza on the Fetus or Newborn? In the pandemics of 1918 and 1957, pregnancy was interrupted in half of influenza cases complicated by pneumonia Case Reports: Stillbirths/neonatal deaths associated with maternal infection with influenza Jewett JF. NEJM 1974;291:256. Yawn et al. JAMA 1971;216:1022.

39 Vaccination Benefits High-Risk Groups Risk hospitalization/death due to respiratory disease Among older adults, 90% of deaths from pneumonia and influenza (CDC. MMWR. 2005;54(RR-08):3) Hospitalization for pneumonia/influenza Unvaccinated elderly: Previously healthy 8.2/1000 High-risk medical condition 38.4/1000 (yr 1) After vaccination: 29.3/1000 (yr 2) 48% in hospitalization or death (yr 1) 31% in hospitalization or death (yr 2) (Hak E et al. Clin Infect Dis 2002;35: ) Absolute risk reduction: 2.4 to 4.7X higher in those with high-risk medical conditions (Hak E et al. Clin Infect Dis 2002;35: )

40 Bordetella pertussis Hack! Hack!! Hack! Hackalougie!! Ahem!!!! Wheeze!!!

41 Bordetella pertussis Highly infectious Incubation period 7 10 days (range 4 21) Insidious onset of symptoms Fever minimal

42 Reports of Pertussis United States, , Cases (Thousands) , CDC. Summary of notifiable diseases United States, Published April 22, 2005, for MMWR 2003;52(No. 54): CDC. Summary of notifiable diseases United States, Published June 16, 2006, for MMWR 2004;53(No. 53):19. CDC. Reported cases of notifiable diseases, by geographic division and area United States, MMWR 2006;55:890.

43 Pertussis Case Reports by State CA AK OR WA NV ID UT AZ HI MT WY CO NM ND SD NE 2005 KS TX OK MN IA MO WI AR LA IL MS IN MI TN AL OH KY WV GA PA FL VA NC SC VT NY ME NH MA CT RI NJ DE MD N=25, cases cases cases >1000 cases CDC. Final 2005 Reports of Notifiable Diseases. MMWR 2006;55:890..

44 Bordetella pertussis The Illness Three Stages of Disease Catarrhal: Paroxysmal: Cough: Convalescence: 1 2 weeks Mild runny nose Mild fever Occasional cough 1 6 weeks Bursts of numerous, rapid coughs followed by long inspiratory effort ( whoop in young children) Can have vomiting/cracked ribs ~15 spells/24 hrs, worse at night Weeks to months

45 Case: A 25 yo female presents with a non-productive cough, now in it s 2 nd to 3 rd week Q What is the likelihood she has pertussis? a) 5% b) 15% c) 25% d) How would I know?

46 Percent Adolescents and Adults with Pertussis With Prolonged Cough # Days Adolescents Adults Coughing (10 19 yrs) ( 20 yrs) 7 98% 97% 14 94% 93% 21 84% 84% 28 76% 74% Farizo KM, et al. Clin Infect Dis.1992;14:

47 % Adolescents/Adults Who Presented with a Prolonged Cough Illness Who Had a Diagnosis of Pertussis Cough (minimum Avg Duration Author days prolonged ) Cough Mink % ( 6 days) 21 days Wright % ( 14 days) 26 days Strebel % ( 7 days) 42 days Gilberg % ( 7 days) 49 days 1. Mink CM et al. Clin Infect Dis 1992;24: Wright SW et al. JAMA 1995;273: Strebel P et al. J Infect Dis 2001;183: Gilberg S et al. J Infect Dis 2002;186:

48 Epidemiology Pertussis Recently, persons beyond childhood (i.e., adolescents and adults) seem to be at greater risk for pertussis Waning immunity? Concerns: Conduits of disease for non-immune infants vulnerable to severe disease Infants suffer most of the morbidity of pertussis and nearly all of the mortality Significant discomfort and lost productivity for older victims

49 Back to the 25 yo female with non productive cough How do you diagnose pertussis??? What is the Gold Standard? Are any other tests available??

50 Diagnosis Bordetella pertussis Test Specificity Sensitivity Culture nasopharynx within 2 wks Sx 100% 20 80% Dacron swab on selective media (Regan Lowe or Bordet-Gengou) Pertussis PCR 97.1% 93.5% Limited availability Not standardized May be too sensitive Culture should also be performed Pertussis DFA 100% 60% NOT recommended Pertussis Single-Sample Serology anti-pt IgG and anti-pt IgA Becoming more accessible Accurate indicators of disease under best circumstances Cutoff points vary by lab MMWR 2005;54(RR-14):1 16.

51 My patient first started coughing 2 weeks ago. Which test is best? From time of first symptoms patient first feels sick and before significant cough starts Culture positive ~ 2 weeks PCR stays positive ~ 4 weeks Serology takes 10 days to become positive Focus Technologies, a commercial lab (Cypress, CA), has a 4 5 day turnaround time

52 Diagnosis Clinical Symptoms in Adolescents and Adults Clinical Finding yo 20 yo Paroxysms 82 83% % Whoop 30 47% 7 82% Apnea 19 32% 29 37% Cyanosis 6 15% 9 12% Vomiting 45 53% 17 62% Hospitalization % % Schmitt-Grohe S et al. Clin Infect. Dis 1995;21: Wright SW et al. JAMA 1995;273: Yih WK et al. J Infect Dis 2000;182:

53 Pertussis Beyond Symptoms Adolescents average 5 days absence from school Adults average 7 days off work Patients experience ~14 days of disturbed sleep Coughing episodes exacerbated by eating and drinking De Serres G et al. J Infect Dis 2000;182:

54 So, I have made the diagnosis in this 25 yo female with 2 3 weeks of cough Do I treat her??? If so, what will I prescribe??? Are there any other considerations???

55 Treatment Bordetella pertussis Treatment May not patient s symptoms, but will clear carriage in nasopharynx Azithromycin 500 mg day 1, 250 mg x 4 days, or Erythromycin 500 mg QID x 14 days, or TMP-SMZ BID x 14 days Post Exposure Same dose regimen, within 3 weeks if close contact (within 3 feet or in closed space) MMWR 2005;54(RR-14):1 16.

56 Close contact?

57 Given that pertussis is Common Bad all that broken rib, vomit, poor sleep stuff Hard to diagnose Contagious VERY BAD in infants

58 Get OFF the Merry-Go-Round VACCINATE!!

59 Use of Tdap in Adolescents ACIP/AAP Recommendations ALL adolescents aged years should receive a single booster dose of Tdap instead of Td Preferred age for Tdap vaccination is years Adolescents who already received Td are encouraged to receive Tdap 5-year interval since Td preferred, but an interval as short as 2 years is acceptable, especially in situations of risk (e.g., outbreak, contact with infant) CDC MMWR 2006;55(RR-3):1 43. AAP Pediatrics 2006;117:

60 Use of Tdap in Adolescents ACIP/AAP Recommendations Administer all indicated vaccines during same visit Separate syringe Different anatomic site OK to give with Meningococcal conjugate vaccine (MCV4) HPV vaccine yo time becoming another vaccination platform CDC MMWR Mar 2006;55(RR-3):1 43. AAP Pediatrics Dec 2006;117:

61 Use of Tdap in Adults ACIP Recommendations Routine recommendation for adults aged yrs: Single dose to adults who received their last Td immunization 10 years ago Interval as short as 2 yrs since last Td may be used, especially in settings of risk (e.g., outbreaks, contact with infants) Prevention of pertussis among infants <12 months Adults who anticipate having close contact with infants (e.g., parents, childcare and healthcare givers) should receive Tdap at least 1 month before beginning contact Other recommendations: Adults who require tetanus vaccination as part of wound management should receive Tdap over Td (March 2006)

62 Use of Tdap in Health Care Personnel (HCP) ACIP Recommendations HCP with direct patient contact in hospitals or ambulatory care settings should receive a single dose of Tdap as soon as feasible PRIORITY for HCP with direct contact with infants Interval as short as 2 yrs since last Td recommended Other HCP should receive Tdap according to routine recommendations Interval as short as 2 years since last Td encouraged Hospitals and ambulatory care facilities should provide Tdap for HCP and use approaches that maximize vaccination rates Education, convenience no charge (March 2006)

63 Use of Tdap During/After Pregnancy Recommendations Routine POSTPARTUM USE of Tdap To women who have not previously received it Before discharge from hospital 2 yrs since last Td, shorter intervals can be used Pregnant women whose last Td given 10 yrs ago Can defer vaccination until after delivery if sufficient tetanus protection likely Age <30 yrs, complete childhood series, and >1 Td dose; or age >30 yrs, complete childhood series, and >2 Td doses; or serum tetanus antitoxin >0.1 IU/mL Give Tdap postpartum ACIP recommends Td during 2 nd or 3 rd trimester MMWR 2008;57(No. RR-4):1 18.

64 Use of Tdap During/After Pregnancy Recommendations (continued) Physicians can choose to give Tdap instead of Td during pregnancy in some situations of risk for pertussis: High incidence in community Wound prophylaxis Pregnant women who are healthcare or child care providers Discuss pros and cons with pregnant woman Register case with manufacturer s pregnancy registry MMWR 2008;57(No. RR-4):1 18.

65 Use of Tdap During/After Pregnancy Recommendations 2007 Red Book for Pediatrics Pregnancy not a contraindication Pregnant adolescents same consideration as non-pregnant Use in 2 nd or 3 rd trimester, to avoid association with adverse pregnancy outcomes more common in 1 st trimester Postpartum, if did not receive previously AAP recommendations for use of Tdap vaccines in pregnant adolescents may differ from those of the CDC Advisory Committee on Immunization Practices.

66 Tdap During or After Pregnancy? Controversy ACOG and AAP in support of using vaccine in pregnant women Maternal IgG antibody transferred to fetus in high levels during 3rd trimester Most vulnerable time for infant exposure is 0 4 months of age Would high maternal-to-fetal transfer of IgG protect infants in the most vulnerable time (0 4 mos)? Only 1/3 of family member exposures were from the mom Do you get a 2 for 1 bonus by boosting the mom during the last trimester? ACIP states can All agree: Vaccinate postpartum if not intrapartum

67 Interference with Fetal Response to DTP Series Controversy Protective level of antibodies for infants not clearly established Do infants who start with high IgG due to transplacental transfer have a less robust response to the infant vaccine series? Studies from 1980 s suggest yes (whole cell vaccine) Some newer studies do not support this Definitive studies now underway ACIP states can use Tdap in pregnancy but does not recommend it All agree: Vaccinate postpartum if not intrapartum

68 ADACEL Experience in Canada ADACEL licensed in Canada May 1999 NACI issued a supportive statement, but at that time did not give a recommendation for universal routine use 3 provinces or territories launched ADACEL vaccination programs Health Canada. CCDR 2000;26(ACS-1):1 8.

69 Pertussis Incidence and Vaccine Use, Canada s Northwest Territories Average Yearly Cases / 10, Switch to PENTACEL ADACEL begun Kandola K. Can J Infect Dis Med Microbiol 2004;15:351.