Flu and Pneumo (Vaxigrip and Pneumo23) Dennis S. Quiambao, MD Medical and Government Affairs Manager

Influenza

"An unvarying disease caused by a varying virus" Influenza "An unvarying disease caused by a varying virus" Kilbourne, 1980

Influenza Worldwide: 10% of the population gets the flu USA: more than 200,000 people are hospitalized from flu complications; and about 36,000 people die from flu. Philippines: 5th leading cause of morbidity Rate per 100,000 population: 414.6

Different Types of Influenza Virus Type A most serious type most common form, usually breaking out every two or three years Type B Type C

Why be concerned about influenza? Absenteeism, income and learning opportunities lost Presenteeism Cause complications, hospitalization and death among the high-risk groups The looming threat of a pandemic due to a novel virus

Who should be vaccinated? Asthmatics Chronic bronchitis patients Diabetics Kidney and liver disease patients >50 years old Children 6months – 5 years old Immunocompromised Health care workers Anyone who wishes to be vaccinated

Annual Flu Vaccination in Adults, Current Local Recommendations: Recommended by: Philippine College of Chest Physicians Philippine Society for Microbiology and Infectious Diseases Philippine Foundation for Vaccination

Contraindication True allergy to chicken eggs

Possible adverse events Soreness, redness or swelling at the injection site Low grade fever Muscle aches

Preventing Influenza Each year a new vaccine is prepared which when given can prevent influenza WHO recommends which viral strains will be included in the vaccine Vaccine is about 89% effective in preventing disease, and for the 11% not covered by the vaccine, the illness caused by the virus is milder because of partial protection from the viral strains in the vaccine (cross protection)

Southern Hemisphere Recommendation 2012 an A/California/7/2009 (H1N1)-like virus; an A/Perth/16/2009 (H3N2)-like virus; a B/Brisbane/60/2008-like virus

Seasonal Occurrence of Influenza

Vaccine Manufacturing Time Lines J S O N D F WHO (Northern hemisphere) PRODUCTION INTERNATIONAL SURVEILLANCE NETWORK VACCINE MANUFACTURER MELBOURNE (Southern hemisphere) Choice of strains Vaccine on time

Timing of Influenza Vaccination Vaccination should be given once a year preferably from February to June The Southern Hemisphere vaccine which is made available starting February of each year is recommended to cover the expected increase in influenza activity from June to November.

Influenza: Frequently Asked Questions

Can the flu shot give me the flu? No, the flu shot cannot cause flu illness. The three influenza viruses contained in the flu vaccine are each inactivated (killed), which means they cannot cause infection.

Why do I need to get vaccinated against the flu every year? Vaccine against influenza viruses change from year to year, which means two things. First, you can get the flu more than once. The immunity that is built up from having the flu caused by one virus strain doesn't always provide protection when a new strain is circulating. Second, a vaccine made against flu viruses circulating last year may not protect against the newer viruses. That is why the influenza vaccine is updated to include current viruses every year. Another reason to get flu vaccine every year is that after you get vaccinated your immunity declines over time and may be too low to provide protection after a year.

Does the flu vaccine work right away? No. It takes about two weeks after vaccination for antibodies to develop in the body and provide protection against influenza virus infection. In the meantime, you are still at risk for getting the flu. That's why it's better to get vaccinated early before the flu season really gets under way.

Pneumococcal Disease

High Burden of Disease Serious pneumococcal infections are a major global health problem A leading cause of death and morbidity in all ages, in both developed and developing world WHO estimates 11 to 20 M hospitalizations from pneumonia occur each year in developing countries At least 1M children die every year from pneumococcal infections – primarily pneumonia and meningitis- including >800,000 children under 5 years old

Steptococcus Pneumoniae: The bacterium Also called « pneumococcus » It’s polysaccharide capsule protects the bacterium against attack from the immune system There are at least 90 different serotypes of S. pneumoniae [1] The 10 most common serotypes are estimated to account for about 62% of invasive diseases worldwide [2] Steptococcus Pneumoniae: The bacterium References: [1] Fedson DS, Musher D. In: Plotkin A, Orenstein WA editors. Vaccines. 4th ed. Philadelphia, USA: WB Saunders Company; 2004. p. 529-88 [2] National Immunization Program, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. PINK BOOK. Pneumococcal Disease. Streptococcus pneumoniae. In: Atkinson W and Wolfe C eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 10th ed. Atlanta (GA): Department of Health & Human Services, Centers for Disease Control and prevention ed; 2007.p 257-70 [1] Fedson and Musher. In: Vaccines, 4th ed., 2004 [2] PINK BOOK. 10th edition February 2007 22

S. Pneumoniae: Transmission and colonization Colonization: S. Pneumoniae is common inhabitant of the respiratory tract and may be isolated from the nasopharynx of 5% to 70% of healthy adults [1a] Humans may carry the bacteria without being infected but may still pass on the bacteria to others Transmission: Person-to-person via respiratory droplets/secretions OR Autoinoculation in asymptomatic carriers [1b] Nasopharynx: site of colonization Trachea Inhalation Patient with pneumococcal disease Asymptomatic carrier Aerosol Nasal cavity Dissemination S. Pneumoniae: Transmission and colonization S. pneumoniae is an exclusively human pathogen [1c]. References: [1] National Immunization Program, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. PINK BOOK. Pneumococcal Disease. Streptococcus pneumoniae. In: Atkinson W and Wolfe C eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 10th ed. Atlanta (GA): Department of Health & Human Services, Centers for Disease Control and prevention ed; 2007.p 257-70 [2] Musher DM. Streptococcus pneumoniae. In Mandell G, Bennett JE, Dolin R editors. Principles and practice of infectious disease. 4th ed. New York, USA: Churchill Livingstone, Inc.; 1995. p. 1811-26. [1] PINK BOOK. 10th edition February 2007 [2] Adapted from Musher DM. Streptococcus pneumoniae 1995 23

S. Pneumoniae: Pathogenesis Breach of blood-brain barrier Bacteraemia Sinusitis CSF leakage Meningitis Otitis media Nasopharyngeal colonization Pneumonia of phagocytic defenses Breach of mucociliary defenses Peritonitis Arthritis arc S. Pneumoniae: Pathogenesis Disease is usually caused by spread from the initial site of colonization. Pneumococcal proliferation in the middle ear causes otitis media; proliferation in the alveoli of the lungs causes pneumococcal pneumonia. (Both are non-invasive pneumococcal diseases.) Bacteraemia (invasive pneumococcal disease) occurs when pneumococci gain entry to the blood. Meningitis is caused by pneumococcal invasion of the cerebrospinal fluid (CSF). Reference: [1] Salyers AA, Whitt DD. Streptococcus pneumoniae. In: Bacterial Pathogenesis: A Molecular Approach. 2nd ed. Washington, USA: ASM Press; 1994. p. 322-31. Adapted from [1] Salyers & Whitt. In: Bacterial Pathogenesis: A Molecular Approach. 1994 24

Factors predisposing to pneumococcal disease Age [1] Age-related impairment of the immune system and other defense mechanisms Decreased physical activity Chronic diseases Poor nutrition Factors predisposing to pneumococcal disease [1] Many factors may contribute to the increased susceptibility of elderly persons to pneumococcal diseases. In older people, the immune system is less effective and natural defences to pneumococcal infection such as the cough and gag reflexes may be impaired. Other factors, such as poor nutrition or underlying chronic illness may further increase the risk of infection. Reference: [1] Musher DM. Streptococcus pneumoniae. In Mandell G, Bennett JE, Dolin R editors. Principles and practice of infectious disease. 4th ed. New York, USA: Churchill Livingstone, Inc.; 1995. p. 1811-26. INCREASED RISK OF SEVERE PNEUMOCOCCAL DISEASE [1] Musher DM. In Mandell G, Bennett JE, Dolin R editors. Principles and practice of infectious disease.4th ed. New York, USA: Churchill Livingstone, Inc.; 1995. p. 1811-26 25

Factors predisposing to pneumococcal disease Chronic illness [1a] Cardiovascular disease Pulmonary disease Diabetes Liver cirrhosis Factors predisposing to pneumococcal disease Pneumococcal infections are more frequent and more severe in patients with chronic conditions. [1b] A high number of patients with pneumococcal infection have diabetes mellitus, a condition in which PMN chemotaxis is reduced and phagocytic function is defective, especially if renal insufficiency is also present [2a] . Susceptibility to pneumococcal infection is also greatly increased in persons with altered pulmonary clearance (e.g. chronic bronchitis, asthma, or chronic obstructive pulmonary disease. [2b] Prior respiratory viral infection, especially influenza, seems to play an important role in susceptibility to pneumococcal infection, potentially through the enhanced adherence of pneumococci to nasopharyngeal cells of persons with viral infection and their lower clearance from the airways because of viral-induced damage [2c]. Also, clinical and epidemiologic observations strongly support the general belief that smoking predisposes to pneumococcal infection [2d]. In a recent risk-factor study among immunocompetent adults aged 18-64 years, smoking conferred a greater risk of PID than any other studied factor. People with PID were 4.1 times more likely to be smokers, and the association increased with the number of cigarettes smoked and the number of years of smoking [3]. Chronic alcoholism is also associated with a high risk of pneumococcal infection, probably because of multiple risk factors. [2d] References [1] Center for Diseases Control and Prevention. Prevention of pneumococcal disease. Recommendations of the Advisory Committee on Immunization Practices. MMWR 1997; 46 (N° RR-8): 1-24. [2] Musher DM. Streptococcus pneumoniae. In Mandell G, Bennett JE, Dolin R editors. Principles and practice of infectious disease. 5th ed. New York, USA: Churchill Livingstone, Inc.; 2000. p. 2128-47. [3] Whitney CG, Schaffner W, and Butler JC. Rethinking Recommendations for Use of Pneumococcal Vaccines in Adults. Clin Infect Dis, 2001; 33(5): 662-75 RISK OF DECOMPENSATION OF THE UNDERLYING DISEASE AND INCREASED RISK OF SEVERE PNEUMOCOCCAL DISEASE [1] CDC. Prevention of pneumococcal disease. Recommendations of the ACIP. MMWR 1997; 46 (N° RR-8): 1-24 26

Factors predisposing to pneumococcal disease Immunodeficiency [1] INCREASED RISK OF SEVERE PNEUMOCOCCAL DISEASE Immunosuppressive therapies Organ transplantation Cancers (e.g. lymphomas, myelomas) HIV Infection Sickle cell anaemia Haematological neoplasms Factors predisposing to pneumococcal disease A functioning immune system is necessary to protect against Streptococcus pneumoniae. [2] Defective antibody formation (congenital or acquired and whatever the cause), has the greatest impact on susceptibility to pneumococcal infection [3a]. Immunodeficiency may occur as a result of a specific disease, or as a side effect of a particular therapy. [4] The prevalence of a pneumococal infection is increased among individuals with human immunodeficiency virus (HIV) infection. [1] HIV infection alters host defense at several points, but defective antibody production probably predominates in the predisposition to pneumococcal infection [3b]. Patients undergoing organ transplantation are given immunosupressive therapy to prevent rejection of the transplant. References [1] Musher DM. Streptococcus pneumoniae. In Mandell G, Bennett JE, Dolin R editors. Principles and practice of infectious disease. 4th ed. New York, USA: Churchill Livingstone, Inc.; 1995. p. 1811-26. [2] Obaro SK, Monteil MA, Henderson DC. The pneumococcal problem. BMJ. 1996 Jun 15;312(7045):1521-5. [3] Musher DM. Streptococcus pneumoniae. In Mandell G, Bennett JE, Dolin R editors. Principles and practice of infectious disease. 5th ed. New York, USA: Churchill Livingstone, Inc.; 2000. p. 2128-47. [4] Center for Diseases Control and Prevention. Prevention of pneumococcal disease. Recommendations of the Advisory Committee on Immunization Practices. MMWR 1997; 46 (N° RR-8): 1-24. [1] Musher DM. In Mandell G, Bennett JE, Dolin R editors. Principles and practice of infectious disease. 4th ed. New York, USA: Churchill Livingstone, Inc.; 1995. p. 1811-26 27

Factors predisposing to pneumococcal infection Environmental factors Very close contact Nursing homes/ hospitals for elderly persons Prisons Shelters for homeless persons Factors predisposing to pneumococcal infection Although not contagious, as is, for example, influenza, the Streptococcus Pneumoniae is easily transmitted between people living in very close contact. [1] Outbreaks can occur, especially among groups with other predisposing factors for pneumococcal disease (e.g. among elderly persons in nursing homes) and among those living in overcrowded conditions. [2] Outbreaks do not occur under conditions of ‘normal’ social contact, such as in schools or in the workplace. [1] References: [1] Musher DM. Streptococcus pneumoniae. In Mandell G, Bennett JE, Dolin R editors. Principles and practice of infectious disease. 4th ed. New York, USA: Churchill Livingstone, Inc.; 1995. p. 1811-26. [2] National Immunization Program, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. PINK BOOK. Pneumococcal Disease. Streptococcus pneumoniae. In: Atkinson W and Wolfe C eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 10th ed. Atlanta (GA): Department of Health & Human Services, Centers for Disease Control and prevention ed; 2007.p 257-70 PREDISPOSITION TO PNEUMOCOCCAL INFECTION [1] Musher DM. In Mandell G, Bennett JE, Dolin R editors. Principles and practice of infectious disease. 4th ed. New York, USA: Churchill Livingstone, Inc.; 1995. p. 1811-26 28

10 Leading Causes of Morbidity 2007, FHSIS Data, Philippines

Pneumococcus: Diversity of Serotypes There are at least 90 different serotypes of S. pneumoniae1,2 Each has a capsule of a different chemical composition Each stimulates the production of a different antibody Only a minority of serotypes cause most cases of human disease 8-10 cause two-thirds of serious pneumococcal infections in adults3 1 Fedson, Musher, in Vaccines, 1994 2 Henrichsen, J Clin Microbiol, 1995 3 UK DoH, Immunisation Against Infectious Disease, 1996

Pneumococcal Vaccines: Antigen Composition 23-valent pneumococcal vaccine contains purified capsular polysaccharides derived from 23 S. pneumoniae serotypes1 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A,11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F Serotype coverage2,3 85-90% of serotypes responsible for all cases of invasive pneumococcal disease Vaccine includes major serotypes that have developed antimicrobial resistance Cross protection within some serotypes1 For example, antibody response to serotype 6B protects against serotype 6A, which is not in the vaccine 1 CDC, MMWR, 1989 2 Fedson, Musher, in Vaccines, 1994 3 Geslin et al., Méd Mal Infect, 1992

Pneumococcal Disease Prevention: Vaccination Recommendations WHO view (Technical Advisory Group convened by WHO Regional Office for Europe, 1988)1 Pneumococcal vaccination should be recommended for all elderly persons (aged ³60-65 years) and for persons of any age at high risk of acquiring pneumococcal infection National recommendations Many countries recommend vaccination for specific at-risk groups or conditions Some countries recommend vaccination for elderly persons aged: ³60 years: Belgium, Germany, Iceland ³65 years: Denmark, Finland, Norway, Sweden, USA, Canada, New Zealand 1 Fedson et al., Infection 1989

Local associations that recommend pneumococcal vaccination Philippine Foundation for Vaccination (PFV) Philippine Society for Microbiology and Infectious Diseases (PSMID) Philippine College of Chest Physicians (PCCP)

Pneumococcal Vaccination Recommendation Age > 60 yrs (routinely): once If < 60 yrs but with the following conditions: Chronic illnesses (Cardio,COPD, Chronic Tuberculosis*, Bronchiectasis, diabetics, cirrhosis, CSF leaks) Immunocompromised (lymphoma, leukemia) Chronic renal failure, nephrotic syndrome Transplant patients Patients on chemo/ radio therapy HIV/ AIDS functional or anatomic asplenia