Pneumococcal vaccination. The approach in Would that work?

Transcription

1 Pneumococcal vaccination. The approach in Would that work? Adrian Brink Clinical Microbiologist, Ampath National Laboratory Services, Milpark Hospital, Johannesburg and Associate Senior Lecturer, Division of Infectious Diseases & HIV Medicine, Department of Medicine, University of Cape Town, Cape town, South Africa

2 Scope of the presentation

3 Scope of the presentation Introduction Burden of CAP and pneumococcal disease Pneumococcal vaccine concepts PPV23 vs PCV13 Risk factors for pneumococcal disease Pneumococcal vaccination recommendations for adults Other vaccine recommendations for adults? Conclusion

4 Introduction

5 Introduction Elderly people suffer high rates of morbidity and mortality due to infectious diseases. Influenza, pneumococcal disease and herpes zoster have their highest mortality rates in older adults For some diseases, even though the illness is less severe in adults they can still transmit the infection to vulnerable groups. For example, adult household contacts have been identified as the major source of pertussis infection in young infants (who are most at risk of hospitalisation and death due to pertussis) Reduced immunity in adults due to incomplete or missed childhood vaccine doses plays a role in the burden of disease. For example, measles disease outbreaks in countries without endemic measles, have been linked to virus imported from non-immune young adult travellers

6 Burden of pneumonia and pneumococcal disease

7 Leading causes of annual deaths worldwide from infectious diseases (all ages) Respiratory infections Diarrhoeal disease HIV/AIDS 1.8 Tuberculosis 1.3 Malaria 0.8 Meningitis Pertussis Of an estimated 58.8 million annual deaths worldwide,15 million (25.5%) are believed to be caused by infectious diseases Measles Hepatitis B Other infectious diseases 1.2 Fauci AS, et al. N Engl J Med. 2012;366: No. of deaths (millions)

8 CAP aetiology and pneumonia severity PSI I-III (%) PSI IV (%) PSI V (%) S. pneumoniae H. influenzae M. catarrhalis Legionella pneumophila M. pneumoniae C. pneumoniae Virus S. aureus Gram-negative bacteria P. aeruginosa mixed Herrero FS, et al. Semin Respir Crit Care Med. 2012;33:

9 Pneumococcal vaccine concepts PPV23 vs PCV13

10 What is Immunosenescence? The quality of the immune system declines with advancing age resulting in increased susceptibility to infection and pathological conditions relating to inflammation (co-morbidities) or autoimmune disease The change in the immune system that occurs with advancing age is termed immunosenescence Caruso C et al. Immunity & Aging 2008;6:10-14

11 Most bones contain haematopoietic bone marrow B-cell pool Serum electrophoresis Red bone marrow High level of early B-cell progenitors Neonate or infant Large number of naïve B- cells of diverse specificity Small numbers of memory B-cell clones Memory B-cell and plasma-cell pool Naive B-cell pool M spike (benign monoclonal gammopathy) Serum electrophoresis Yellow bone marrow Fat deposits survival niches? B-cell progenitors Elderly indivual Decreased haematopoietic bone marrow production of naïve B cells Accumulation of memory B cells and plasma cells Limited specificities Siegrist C-A et al. Nature Reviews Immunology 2009; 9:

12 Challenges with vaccinating older individuals The elderly have reduced innate and adaptive immune function which results in: Impaired local responses at the site of vaccine injection 1 Reduced primary immune responses to new antigens 1 Reduced efficiency for memory B cells and decrease revaccination response 1 Reduced functionality of antibodies, and reduced phagocytic killing capacity of neutrophils 2 Reduced long-term protective effect of vaccination 1 At the same time, vaccination is an important strategy to prevent infection and protect vulnerable, older people Weinberger B et al. CID 2008:46: Simell B et al. Vaccine doi: /j.vaccine

13 Strategies to improve vaccine efficacy in the elderly Adjuvants / Formulations TLR / NLR agonists Inducers of inflammatory cytokines Stimulate ACP activation & migration Route of immunization IL-7 Expand T cells & increase repertoire size UD vs SC/IM Mucosal route(s)? PS immunization Use conjugates? How can we improve vaccination in the elderly? Dose High dose Live or killed vaccines Other strategies Sport, mental training, nutritrion control Schedules Vaccinate in «early days» Induce memory cells, which would be recalled more efficiently at older ages Guy B. J Comp Pathol 2010; 142: S133-S137

14 History of pneumococcal vaccines 1881 Pneumococcal bacterium discovered Two 6-valent polysaccharide vaccines vaccines were marketed valent polysaccharide vaccine was licensed 1 Conjugated Vaccines valent conjugate vaccine (PCV7) was licensed for children PCV13 licensed for adults aged 50 yrs The first large-scale trial of a crude whole-cell pneumococcal vaccine was conducted valent conjugate vaccine (PCV13) was licensed for children valent polysaccharide vaccine (PPV) was licensed 1 1. CDC. Pneumococcal disease. In: Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed. Washington DC: Public Health Foundation, Williams C, et al. J Infect 2008;56: Targonski PV, et al. Cleve Clin J Med 2007;74: Prevnar 13 (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM 197 Protein]) Prescribing Information, Wyeth Pharmaceuticals Inc.

15 There are currently 2 pneumococcal vaccines available for adults Vaccine Serotypes Additional Serotypes Conjugate PCV13 1 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F, 19A Polysaccharide PPSV 2 Included (except 6A) 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, 33F PCV13=13-valent pneumococcal conjugate vaccine; PPSV=pneumococcal polysaccharide vaccine. 1. Prevenar 13 [summary of product characteristics]. Kent, UK: Pfizer Limited. 2. Pneumovax 23 [summary of product characteristics]. Berkshire, UK: Sanofi Pasteur MSD Limited.

16 Plain polysaccharide vaccines The antigens targeted by the vaccine are specific serotypes of the polysaccharide capsule 25 to 50 mcg of polysaccharide per serotype

17 Polysaccharide-CRM197 conjugate (complex crosslinked conjugate) Polysaccharide 2 to 4 mcg of polysaccharide per serotype CRM 197 carrier protein The antigens targeted by the vaccine are specific serotypes of the polysaccharide capsule

18 Immunology of pneumococcal vaccines Polysaccharide antigens Immunogenic carrier protein Conjugate vaccine + = PPV23 PCV13 A polysaccharide (ps) is chemically linked (conjugated) to a protein carrier 1 1. Pollard AJ et al. Nat Rev Immunol 2009;9:

19 Immunology of pneumococcal vaccines Polysaccharide antigens Immunogenic carrier protein Conjugate vaccine + = Presentation B cell T cell B cell Plasma cell T-independent Memory B cell T-dependent Plasma cell The conjugation of a polysaccharide to a carrier protein leads to the interaction with T cells resulting in the release of functional antibodies and production of memory B cells 1,2 de Roux A et al. Clin Infect Dis 2008;46(7): Pollard AJ et al. Nat Rev Immunol 2009;9:

20 Pneumococcal vaccine effectiveness against invasive pneumococcal disease (IPD) Vaccine effectiveness (%) < Age (years) Jackson LA et al. Clin Infect Dis 2008; 47:

21 GMC micro/ml GMC micro/ml PPV reduces the response to subsequent doses of the vaccine Type Type Type 7F A B C D E 0 A B C D E 0 A B C D E Type Type 18C Type 19F A B C D E 0 A B C D E 0 A B C D E Törling et al, Vaccine 2003; 22:96-103

22 Perceived strengths of PCV Conjugate vaccines Immune memory 1 Booster effect 3 No hyporesponsivenes 1 Reduction of carriage 2, contributes to herd effect 3 Prolonged protection 1,3 In addition, significant impact on resistant pneumococcal infections 1 Blanchard-Rohner et al, Expert Rev Vaccines, 10: , Makela et al, Expert Rev Vaccines, 1: , Pollard et al, Nat Rev Immunol, 9: , 2009

23 Rapid impact of PCV on antibiotic non-susceptible (NS) IPD Children < 2 years Incidence (cases per 100,000 person-years) Penicillin: -82% (-85% to -78%)* PCV7 Penicillin Multidrug resistance (MDR) Ceftriaxone MDR: -84% (-88% to -79%)* PCV Ceftriaxone: -85% (-91% to -77%)* Time (years) Von Gottberg et al. N Engl J Med 2014;371:

24 Rapid impact of PCV on antibiotic non-susceptible (NS) IPD Children < 2 years Incidence of Disease (cases per 100,000 person-years) Incidence of Antibiotic Resistant Invasive Pneumococcal Disease (IPD) in Children <2 years of age PCV7 Introduced Switch to PCV Penicillin resistant Multidrug resistant (MDR) Ceftriaxone resistant Von Gottberg et al. N Engl J Med 2014;371:

25 Rapid impact of PCV on antibiotic non-susceptible (NS) IPD All ages *Percentage change in IPD incidence: post-vaccine (2012) vs. pre-vaccine ( ) years. PCV7 introduced in April 2009 and replaced with PCV13 in June/July PCV7 Penicillin: -57% (-53% to -60%)* PCV13 Von Gottberg et al. N Engl J Med 2014;371:

26 A phase 4, randomised, placebo-controlled clinical trial of PCV13 efficacy among adults 65 years and older in the prevention of vaccine-serotype pneumococcal CAP and IPD Bonten MJM et al. New Engl J Med 2015; 372:

27 Clinical trial design and timeline 27 During the Flu season study subjects were offered the seasonal TIV Screening and recruitment R 84,496 volunteers Aged 65 years Placebo PCV 13 Accrual of VT-CAP Cases Data lock and analysis Regulatory Review of Primary and Secondary Outcome Data Sept 2008 Jan 2010 Sept 2011 Aug Interim Analysis 130 VT-CAP Episodes R = Randomization Hak E, Grobbee DE, Sanders EAM, et al. Netherlands J Med. 2008;66:

28 Vaccine efficacy (%) CAPiTA efficacy results: primary and secondary objectives Reduction in Pneumococcal Disease With PCV13* 46% p<0.001 Primary end point: prevention of a first episode of VT pneumococcal CAP 45% p=0.007 Secondary end point: prevention of a first episode of VT nonbacteremic/noninvasiv e pneumococcal CAP 75% p<0.001 Secondary end point: prevention of a first episode of VT IPD Statistically significant reductions in first episode of VT pneumococcal CAP with PCV 13 Overall, adverse event profile was consistent with that of prior studies in adults CAP=community-acquired pneumonia; CAPiTA=Community-Acquired Pneumonia Immunization Trial in Adults; IPD=invasive pneumococcal disease; VT=vaccine type. Bonten MJ, et al. N Engl J Med. 2015;372:

29 Duration of protective efficacy extended throughout the 4- year study 1 Cumulative cases All 1st episodes of VT-CAP PCV 13* Placebo Days since vaccination Days since vaccination plots from post hoc analysis Mean duration of follow-up=3.97 years VT-CAP=vaccine-type community-acquired pneumonia. 1. Bonten MJ, et al. N Engl J Med. 2015;372: *Trademark. 29

30 Risk factors for pneumococcal disease

31 Susceptibility to Streptococcus pneumoniae is influenced by host and environmental factors Risk Factors for Invasive Pneumococcal Disease Age 1 2 years 65 years Host factors Immunocompetent 2,3,5,6 Immunocompromised 2,3,5,6 Chronic heart disease Chronic lung disease* Diabetes Functional or anatomic asplenia Chronic liver disease Cerebrospinal fluid leaks HIV infection Chronic renal failure, nephrotic syndrome Cancer (solid, hematologic) Solid organ transplantation Autoimmune diseases Immunosuppressive therapy, corticosteroids Primary immunodeficiencies *Including chronic obstructive pulmonary disease, emphysema, and asthma. HIV=human immunodeficiency virus. Environmental factors 3,4 Preceding viral respiratory infection (eg, influenza) Residence in an institution (eg, nursing home) 1. Centers for Disease Control and Prevention. Active Bacterial Core surveillance (ABCs) report. Emerging Infections Program Network: Streptococcus pneumoniae, Accessed October 10, Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2010;59: Musher DM. Streptococcus pneumoniae. In: Mandell GL, et al, eds. Mandell, Douglas, and Bennett s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA; 2010: Centers for Disease Control and Prevention. Prevention of pneumococcal infections secondary to seasonal and 2009 H1N1 influenza viruses infection. Accessed October 10, van Hoek AJ, et al. J Infect. 2012;65: Klemets P, et al. BMC Infect Dis. 2008;8:96. Behavioral factors 2,3 Smoking Alcohol abuse

32 Cases of invasive disease (per 100,000) Highest incidence and mortality rates of IPD at extremes of age Deaths associated with IPD (per 100,000) Incidence of IPD and associated mortality rates (USA, 2009) 45 Cases Deaths < Age (years) Adapted from Centers for Disease Control and Prevention Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2009.

33 Patients with chronic diseases are at risk of invasive pneumococcal infections Cases/100,000 persons Age-specific incidence of IPD in healthy adults (aged 18 years) vs adults with chronic illnesses, United States, Healthy Chronic heart disease Diabetes Chronic lung disease * Age (years) IPD=invasive pneumococcal disease (includes meningitis, bacteremia, and pneumonia when accompanied by bacteremia). *Chronic heart disease: atherosclerotic cardiovascular disease, angina, congestive heart failure, or (patient surveys) ever told by a health care profession that they had coronary heart disease, angina, or heart attack. Kyaw M et al. J Infect Dis. 2005;192:

34 Chronic medical conditions are significantly more frequent in pneumococcal CAP patients Retrospective, multicenter study of adults ( 18 years) hospitalized with CAP, Barcelona, Spain, (N=241) 1 P <0.05 Streptococcus pneumoniae was the most frequently detected etiological agent. Pneumococcal CAP was identified in 34% of inpatients. P <0.05 P <0.05 CAP=community-acquired pneumonia Sicras-Mainar A, et al. BMC Infect Dis. 2012;12:283

35 How big is the risk?

36 The incidence of IPD in immunocompromised adults aged 50 years and older is estimated to be more than 6 times that of healthy adults 1 Incidence of IPD in adults aged 50 years and older with high-risk conditions* 6.4X Data from a retrospective cohort study from 3 large, longitudinal, US health care databases of medical and outpatient pharmacy claims from *High-risk conditions include congenital immunodeficiency, immunosuppressive drugs, chronic renal failure, diseases of white blood cells, functional/anatomic asplenia, malignant neoplasms, solid organ transplantation, human immunodeficiency virus. IPD=invasive pneumococcal disease.

37 Incidence of IPD in adults aged years with selected underlying conditions USA Cases per 100, 000 persons fold increased risk fold increased risk Kyaw M et al. J Infect Dis. 2005;192(3):

38 Adjusted odds ratio for IPD (95% CI) Cigarette smoking increased the risk of IPD The risk of IPD increased with the number of cigarettes currently smoked per day, suggesting a dose-response relationship Cigarettes/day IPD=invasive pneumococcal disease (includes meningitis, bacteremia, and pneumonia when accompanied by bacteremia). Nuorti JP et al; Active Bacterial Core Surveillance Team. N Engl J Med 2000;342:

39 Pneumococcal vaccination recommendations for adults

40 Current SA situation and recommendations PPV23 recommendations (similar to CDC) Adults aged years Chronic heart disease (including congestive heart failure and cardiomyopathies, excluding hypertension) Chronic lung disease (including chronic obstructive lung disease, emphysema, and asthma) Chronic liver disease (including cirrhosis) Alcoholism Diabetes mellitus Smokers Functional or anatomical asplenia Immunocompromising conditions such as HIV infection Haematological malignancies Transplant patients Also recommended for use in adults aged > 65 years irrespective Feldman et al. SAMJ 1999;89:

41 Current SA situation and recommendations PCV Registered for use in adults in SA, as in other parts of the world, based on initial immunogenicity studies The initial registered indication in SA was the use of a single dose of PCV13 in adults > 50 years 2015 Registration in SA in adults 18 years and older as a single dose Specific groups at high risk for pneumococcal infection were mentioned in the registration including cases with sickle cell disease and HIV infection that were recommended to receive at least one dose of PCV13 whether or not they had received one or more doses of PPV23 previously

42 Adults 19* years with underlying comorbid and immunocompromising conditions are indications for vaccination Comorbid and immuno-compromising conditions include: Congenital or acquired immunodeficiency (including B- or T-lymphocyte deficiency Complement deficiencies Phagocytic disorders excluding chronic granulomatous disease HIV infection Chronic renal failure Nephrotic syndrome Leukemia Lymphoma Hodgkin disease Generalized malignancy Multiple myeloma Solid organ transplant Long term systemic corticosteroids Including iatrogenic immunosuppression (and radiation therapy). Kim et al Ann Intern Med. 2016;164: doi: /m * USA

43 Adults 19* years with underlying comorbid and immunocompromising conditions are indications for vaccination Anatomical or functional asplenia that are indications for pneumococcal vaccination are: Sickle cell disease Other hemoglobinopathies Congenital or acquired asplenia Splenic dysfunction Splenectomy. Pneumococcal vaccines should be given at least 2 weeks before immunosuppressive therapy or an elective splenectomy and as soon as possible to adults who are diagnosed with HIV infection Kim et al Ann Intern Med. 2016;164: doi: /m * USA

44 Prime Boost strategy Sadlier et al Scientific Reports 2016; 6:32076 DOI: /srep32076 A major challenge for immunologists has been the development of vaccines designed to emphasize cellular immune responses. One particularly promising approach is the prime-boost strategy, which has been shown to generate high levels of T-cell memory in animal models. Recently, several papers have highlighted the power of prime-boost strategies in eliciting protective cellular immunity to a variety of pathogens and have demonstrated efficacy in humans. Coupled with recent advances in our understanding of the mechanisms underlying the generation, maintenance and recall of T-cell memory, the field is poised to make tremendous progress.

45 Prime Boost strategy The aim of this study was to compare the immunologic response to a prime-boost immunization strategy combining PCV13 with PPSV23 versus PPSV23 alone in HIV-infected adults. Serotype specific IgG geometric mean concentration (GMC) and functional oposonophagocytic (OPA) geometric mean titer (GMT) were compared for 12 pneumococcal serotypes shared by both vaccines at week 8 and week 28. The prime-boost vaccine group were more likely to achieve a 2-fold increase in IgG GMC and a GMC>1ug/ml at week 8 [(OR) 2.00, 95% CI , p<0.01)] and week 28 (OR 1.95, 95% CI ,p<0.01). Similarly, the prime-boost vaccine group were more likely to achieve a 4-fold increase in GMT at week 8 (OR 1.71, 95% CI , p<0.01) and week 28 (OR 1.6, 95% CI , p<0.01) This study adds to evidence supporting current pneumococcal vaccination recommendations combining the conjugate and polysaccharide pneumococcal vaccines for HIV-infected individuals. Sadlier et al Scientific Reports 2016; 6:32076 DOI: /srep32076

46 Indications for Prime Boost strategy In adults 18 years with severe immuno-compromising or comorbid conditions at high-risk of pneumococcal disease are indications for prime boost pneumococcal vaccination and include: Anatomical or functional asplenia Cerebrospinal fluid leak Cochlear implant HIV infection Also includes all patients 65 years The recommendations are: The use of PCV13 in sequence with PPV23 PCV13 should always preferably be given first. In individuals who have not previously had PPV23 vaccination, the PCV13 vaccine should be given first: Followed by a minimum of 2 months later with the PPV23 vaccine in the case of adults > 19 years of age with the high-risk underlying comorbid and immuno-compromising conditions, and a 2 nd dose of PPV23 at least 5 years later Followed by a minimum of 12 months later with the PPV23 vaccine in adults 65 years of age. No additional doses of PPSV23 are indicated. Kim et al Ann Intern Med. 2016;164: doi: /m

47 Summary of pneumococcal recommendations All adults > 18 yr With severe comorbid or immunocompromised conditions: Who are vaccine naive should receive a single dose of PCV13 followed at least 8 weeks later by PPV23. (And a 2 nd dose of PPV23 at least 5 years later) Who have previously received PPV23 should receive a single dose of PCV13 at least one year later All adults > 50 yrs Who are vaccine naïve should receive a single dose of PCV13 Who have previously received PPV23 should receive a single dose of PCV13 at least one year later All adults 65 yrs Who are vaccine naïve should receive a single dose of PCV13 followed a year later by PPV 23 Who have received PPV23 should receive a single dose of PCV13 at least one year later SA recommendations for adult pneumococcal vaccination High risk for pneumococcal disease Prime Boost strategy (PCV13 followed by PPV23)

48 Summary of pneumococcal recommendations Young adults 18 yr with severe underlying comorbid or immune-compromising conditions All adults 65 years Vaccine naïve Received PPV23 previously Should receive a single dose of PCV13 Should receive a single dose of PCV13 at least 12 months later Followed at least 2 months later by PPV23 Followed at least 12 months later by PPV23 Followed at least 5 years later by a 2 nd PPV23 All adults 50 years Prime Boost strategy (PCV13 followed by PPV23)

49 Summary of pneumococcal recommendations Patients who previously received PPV23 before age of 65yrs who are now aged 65 yrs 1 year Administer PCV13 at least 1 year after the most recent dose of PPSV23 5 years Administer a dose of PPSV23 at least 1 year after PCV13 and at least 5 years after the most recent dose 1 year

50 Current SA situation and recommendations In proposed new SA guideline, should PPV23 in the age group with comorbidities be replaced with PCV13? PPV23 recommendations (similar to CDC) Adults aged years Chronic heart disease (including congestive heart failure and cardiomyopathies, excluding hypertension) Chronic lung disease (including chronic obstructive lung disease, emphysema, and asthma) Chronic liver disease (including cirrhosis) Alcoholism Diabetes mellitus Smokers Functional or anatomical asplenia Immunocompromising conditions such as HIV infection Haematological malignancies Transplant patients Also recommended for use in adults aged > 65 years irrespective Feldman et al. SAMJ 1999;89:

51 Other vaccine recommendations for adults

52 Recommended immunization schedule for adults 19 years Kim et al Ann Intern Med. 2016;164: doi: /m

53 Recommended immunization schedule for adults 19 years by medical condition and other indications Kim et al Ann Intern Med. 2016;164: doi: /m

54 Tetanus, Diphtheria, and accellular Pertussis vaccination CDC recommendations Adults who have not received tetanus and diphtheria toxoids and acellular pertussis vaccine (Tdap) or for whom pertussis vaccination status is unknown should receive 1 dose of Tdap followed by a tetanus and diphtheria toxoids (Td) booster every 10 years. Tdap should be administered regardless of when a tetanus or diphtheria toxoid-containing vaccine was last received. Adults with an unknown or incomplete history of a 3-dose primary series with tetanus and diphtheria toxoid-containing vaccines should complete the primary series that includes 1 dose of Tdap. Unvaccinated adults should receive the first 2 doses at least 4 weeks apart and the third dose 6 12 months after the second dose. Special populations Pregnant women should receive 1 dose of Tdap during each pregnancy, preferably during the early part of gestational weeks 27 36, regardless of prior history of receiving Tdap Kim et al Ann Intern Med. 2016;164: doi: /m Terminology (acronym) relevant to SA as a consequence of available vaccines Tdap-IPV (quadrivalent): Tetanus and reduced amount of diphtheria vaccine with acellular pertussis and inactivated polio vaccine. Td vaccine: Tetanus and reduced amount of diphtheria vaccine

55 Herpes zoster vaccination CDC recommendations General information Adults aged 60 years or older should receive 1 dose of herpes zoster vaccine (HZV), regardless of whether they had a prior episode of herpes zoster. Zoster vaccine, a live virus vaccine, can be administered concurrently with all other live and inactivated vaccines, including those routinely recommended for people 60 years of age or older, such as influenza and pneumococcal vaccines, using separate syringes and injection sites. Zoster and varicella vaccines cannot be used interchangeably. Special populations Adults aged 60 years or older with chronic medical conditions may receive HZV unless they have a medical contraindication, e.g., pregnancy or severe immunodeficiency Adults with malignant conditions, including those that affect the bone marrow or lymphatic system or who receive systemic immunosuppressive therapy, should not receive HZV. Adults with HIV infection and CD4+ T-lymphocyte count <200 cells/μl should not receive HZV. Kim et al Ann Intern Med. 2016;164: doi: /m

56 Measles, Mumps, and Rubella vaccination CDC recommendations General information Adults born in 1957 (SA???) or later without acceptable evidence of immunity to measles, mumps, or rubella (defined below) should receive 1 dose of measles, mumps, and rubella vaccine (MMR) unless they have a medical contraindication to the vaccine, e.g., pregnancy or severe immunodeficiency Acceptable evidence of immunity to measles, mumps, or rubella in adults is: born before 1957, documentation of receipt of MMR, or laboratory evidence of immunity or disease. Documentation of healthcare provider-diagnosed disease without laboratory confirmation is not acceptable evidence of immunity. Special populations Pregnant women who do not have evidence of immunity to rubella should receive 1 dose of MMR upon completion or termination of pregnancy and before discharge from the healthcare facility; non-pregnant women of childbearing age without evidence of rubella immunity should receive 1 dose of MMR Adults with primary or acquired immunodeficiency including malignant conditions affecting the bone marrow or lymphatic system, systemic immunosuppressive therapy, or cellular immunodeficiency should not receive MMR Kim et al Ann Intern Med. 2016;164: doi: /m

57 Measles, Mumps, and Rubella vaccination Special populations (cont) Adults with HIV infection and CD4+ T-lymphocyte count 200 cells/μl for at least 6 months who do not have evidence of measles, mumps, or rubella immunity should receive 2 doses of MMR at least 28 days apart. Adults with HIV infection and CD4+T-lymphocyte count <200 cells/μl should not receive MMR. Adults who work in healthcare facilities should receive 2 doses of MMR at least 28 days apart (healthcare personnel born before 1957 who are unvaccinated or lack laboratory evidence of measles, mumps, or rubella immunity, or laboratory confirmation of disease should be considered) Adults who are students in postsecondary educational institutions or plan to travel internationally should receive 2 doses of MMR at least 28 days apart. Kim et al Ann Intern Med. 2016;164: doi: /m

58 Varicella vaccination CDC recommendations General information Adults without evidence of immunity to varicella (defined below) should receive 2 doses of single-antigen varicella vaccine (VAR) 4 8 weeks apart, or a second dose if they have received only 1 dose Persons without evidence of immunity for whom VAR should be emphasized are: Adults who have close contact with persons at high risk for serious complications, e.g., healthcare personnel and household contacts of immunocompromised persons Adults who live or work in an environment in which transmission of varicella zoster virus is likely, e.g., teachers, childcare workers, and residents and staff in institutional settings Adults who live or work in environments in which varicella transmission has been reported, e.g., college students, residents and staff members of correctional institutions, and military personnel Non-pregnant women of childbearing age; adolescents and adults living in households with children International travellers Special populations Pregnant women should be assessed for evidence of varicella immunity. Pregnant women who do not have evidence of immunity should receive the first dose of VAR upon completion or termination of pregnancy and before discharge from the healthcare facility, and the second dose 4 8 weeks after the first dose. Healthcare institutions should assess and ensure that all healthcare personnel have evidence of immunity to varicella. Kim et al Ann Intern Med. 2016;164: doi: /m

59 Varicella vaccination Special populations (cont) Adults with malignant conditions, including those that affect the bone marrow or lymphatic system or who receive systemic immunosuppressive therapy, should not receive VAR. Adults with HIV infection and CD4+ T-lymphocyte count 200 cells/μl may receive 2 doses of VAR 3 months apart. Adults with HIV infection and CD4+ T-lymphocyte count <200 cells/μl should not receive VAR Kim et al Ann Intern Med. 2016;164: doi: /m

60 Human papillomavirus vaccination CDC recommendations General information HPV vaccination is routinely recommended for children at age 11 or 12 years. For adults who had initiated but did not complete the HPV vaccination series, consider their age at first HPV vaccination and other factors (described below) to determine if they have been adequately vaccinated. Adult females through age 26 years and adult males through age 21 years who have not received any human papillomavirus (HPV) vaccine should receive a 3-dose series of HPV vaccine at 0, 1-2, and 6 months. Males aged 22 through 26 years may also be vaccinated with a 3-dose series of HPV vaccine at 0, 1 2, and 6 months Adult females through age 26 years and adult males through age 21 years (incl males aged 22 through 26 years) who initiated the HPV vaccination series before age 15 years and received 2 doses at least 5 months apart are considered adequately vaccinated and do not need an additional dose of HPV vaccine Adult females through age 26 years and adult males through age 21 years (incl males aged 22 through 26 years) who initiated the HPV vaccination series before age 15 years and received only 1 dose, or 2 doses less than 5 months apart, are not considered adequately vaccinated and should receive 1 additional dose of HPV vaccine Kim et al Ann Intern Med. 2016;164: doi: /m

61 Human papillomavirus vaccination Special population A 3-dose series of HPV vaccine at 0, 1-2, and 6 months should be given to: Men who have sex with men through age 26 years who have not received any HPV vaccine Adult females and males through age 26 years with immuno-compromising conditions (described below), including those HIV infection Pregnant women Are not recommended to receive HPV vaccine, although there is no evidence that the vaccine poses harm. If a woman is found to be pregnant after initiating the HPV vaccination series, delay the remaining doses until after the pregnancy. No other intervention is needed. Pregnancy testing is not needed before administering HPV vaccine. Immunocompromising conditions for which a 3-dose series of HPV vaccine is indicated are primary or secondary immunocompromising conditions that might reduce cell-mediated or humoral immunity e.g: B-lymphocyte antibody deficiencies Complete or partial T-lymphocyte defects HIV infection Malignant neoplasm Transplantation Autoimmune disease Immunosuppressive therapy. Kim et al Ann Intern Med. 2016;164: doi: /m

62 Conclusion

63 Conclusions Leading causes of annual deaths worldwide from infectious diseases (all ages) are RTIs Highest incidence and mortality rates of IPD at extremes of age Patients with chronic diseases are also at risk of invasive pneumococcal infections - chronic heart and lung diseases and diabetes incl HIV infection where PCV has been shown to be effective as opposed to PPSV23 The change in the immune system that occurs with advancing age is termed immunosenescence The conjugation of a polysaccharide to a carrier protein leads to the interaction with T cells resulting in the release of functional antibodies and production of memory B cells

64 Conclusions The CAP immunization trial in adults (CAPiTA) demonstrated the efficacy of Prevenar 13 in the prevention of a 1 st episode of: Vaccine-type (VT) pneumococcal CAP VT non-bacteremic (non-invasive) pneumococcal CAP VT invasive pneumococcal disease Pneumococcal vaccine schedule: The 2 vaccines (PCV 13 and PPSV23) should not be co-administered Prior receipt of PPSV23 within 1 year results in diminished immune responses to PCV 13 compared to PPSV23 naïve individuals and hence, in naïve patients PCV13 should always be administered first Prime-boost strategy aims to elicit protective cellular immunity by generating high levels of T-cell memory, which has proven to be the case for PCV13 High risk patients should be vaccinated irrespective following a primeboost strategy

65