Vaccine4 influenza

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Vaccine 3Vaccine 3

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Influenza

Highly infectious viral illness Epidemics reported since at

least 1510 At least 4 pandemics in 19th century Estimated 21 million deaths worldwide

in pandemic of 1918-1919 Virus first isolated in 1933

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Influenza Virus

Single-stranded RNA virus Family Orthomyxoviridae 3 types: A, B, C Subtypes of type A determined by

hemagglutinin and neuraminidase

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Influenza Virus Strains Type A - moderate to severe illness

- all age groups- humans and other animals

Type B - milder epidemics- humans only- primarily affects children

Type C - rarely reported in humans - no epidemics

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Influenza Virus

A/Fujian/411/2002 (H3N2)

Neuraminidase

Hemagglutinin

Type of nuclearmaterial

Virustype

Geographicorigin

Strainnumber

Year of isolation

Virus subtype

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Influenza Antigenic Changes

Hemagglutinin and neuraminidase antigens change with time

Changes occur as a result of point mutations in the virus gene, or due to exchange of a gene segment with another subtype of influenza virus

Impact of antigenic changes depend on extent of change (more change usually means larger impact)

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Influenza Antigenic Changes Antigenic Shift

– Major change, new subtype

– Caused by exchange of gene segments

– May result in pandemic

Example of antigenic shift– H2N2 virus circulated in 1957-1967

– H3N2 virus appeared in 1968 and completely replaced H2N2 virus

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Influenza Antigenic Changes Antigenic Drift

– Minor change, same subtype

– Caused by point mutations in gene

– May result in epidemic

Example of antigenic drift– In 2002-2003, A/Panama/2007/99 (H3N2) virus

was dominant

– A/Fujian/411/2002 (H3N2) appeared in late 2003 and caused widespread illness in 2003-2004

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Influenza Type A Antigenic Shifts

Year

1889

1918

1957

1968

1977

Subtype

H3N2

H1N1

H2N2

H3N2

H1N1

Severity ofPandemic

Moderate

Severe

Severe

Moderate

Mild

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Impact of Pandemic Influenza

200 million people could be affected Up to 40 million require outpatient visits Up to 700,000 hospitalized 89,000 - 200,000 deaths

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Influenza Pathogenesis

Respiratory transmission of virus Replication in respiratory epithelium with

subsequent destruction of cells Viremia rarely documented Viral shedding in respiratory secretions for

5-10 days

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Influenza Clinical Features

Incubation period 2 days (range 1-4 days)

Severity of illness depends on prior experience with related variants

Abrupt onset of fever, myalgia, sore throat, nonproductive cough, headache

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Influenza Complications

Pneumonia– primary influenza

– secondary bacterial

Reye syndrome Myocarditis Death 0.5-1 per 1,000 cases

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Impact of Influenza

~36,000 excess deaths per year >90% of deaths among persons >65 years

of age Higher mortality during seasons when

influenza type A (H3N2) viruses predominate

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Impact of Influenza Highest rates of complications and hospitalization

among young children and person >65 years Average of >200,000 influenza-related excess

hospitalizations per year since 1969

57% of all hospitalizations among persons <65 years of age

Greater number of hospitalizations during type A (H3N2) epidemics

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Influenza Diagnosis Clinical and epidemiological characteristics Isolation of influenza virus from clinical

specimen (e.g., nasopharynx, throat, sputum)

Significant risk in influenza IgG by serologic assay

Direct antigen testing for type A virus

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Influenza Epidemiology Reservoir Human, animals

(type A only) Transmission Respiratory

Probably airborne Temporal pattern Peak December – March

in temperate areaMay occur earlier or later

Communicability Maximum 1-2 days before to 4-5 days after onset

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Influenza Vaccines

Inactivated subunit (TIV)– Intramuscular

– Trivalent

Live attenuated vaccine (LAIV)– Intranasal

– Trivalent

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Composition of the 2007-2008 Influenza Vaccine*

A/Solomon Islands/3/2006 (H1N1)-like virus;

A/Wisconsin/67/2005 (H3N2)-like virus ; B/Malaysia/2506/2004-like virus ;

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Inactivated Influenza Vaccine Efficacy

70%-90% effective among healthy persons <65 years of age

30%-40% effective among frail elderly persons

50%-60% effective in preventing hospitalization

80% effective in preventing death

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Influenza and Complications Among Nursing Home Residents

Vaccinated* Unvaccinated

RR=1.9 RR=2.0 RR=2.5 RR=4.2

*Inactivated influenza vaccine. Genesee County, MI, 1982-1983

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LAIV Efficacy in Healthy Children

87% effective against culture-confirmed influenza in children 5-7 years old

27% reduction in febrile otitis media (OM) 28% reduction in OM with accompanying

antibiotic use Decreased fever and OM in vaccine

recipients who developed influenza

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LAIV Efficacy in Healthy Adults

20% fewer severe febrile illness episodes 24% fewer febrile upper respiratory illness

episodes 27% fewer lost work days due to febrile

upper respiratory illness 18%-37% fewer days of healthcare provider

visits due to febrile illness 41%-45% fewer days of antibiotic use

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Timing of Inactivated Influenza Vaccine Programs

Actively target vaccine available in September and October to persons at increase risk of influenza complications, children <9 years, and healthcare workers

Vaccination of all other groups should begin in November

Continue vaccinating through December and later, as long as vaccine is available

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Inactivated Influenza Vaccine Schedule

AgeGroup

6-35 mos

3-8 yrs

>9 yrs

Dose0.25 mL

0.50 mL

0.50 mL

No.Doses1* or 2

1* or 2

1

*Only one dose is needed if the child received influenza vaccine during a previous influenza season

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Inactivated Influenza Vaccine Recommendations

All persons 50 years of age or older Children 6-23 months of age Residents of long-term care facilities Pregnant women Persons 6 months to 18 years receiving

chronic aspirin therapy Persons >6 months of age with chronic

illness

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Routine annual TIV vaccination for persons 50 years and older– Up to a third of persons 50-64 years have

high-risk conditions

– Only 35% received influenza vaccine in 1999

– May increase coverage in HCWs

– Reduced sick days

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Persons with the following chronic illnesses should be considered for inactivated influenza vaccine:– pulmonary (e.g., asthma, COPD)– cardiovascular (e.g., CHF)– metabolic (e.g., diabetes)– renal dysfunction– hemoglobinopathy– immunosuppression, including HIV infection

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Pregnancy and Inactivated Influenza Vaccine

Risk of hospitalization 4 times higher than nonpregnant women

Risk of complications comparable to nonpregnant women with high-risk medical conditions

Vaccination (with TIV) recommended if pregnant during influenza season

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HIV Infection and Inactivated Influenza Vaccine

Persons with HIV at higher risk of complications of influenza

TIV induces protective antibody titers in many HIV infected persons

Transient increase in HIV replication reported

TIV will benefit many HIV-infected persons

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Influenza Vaccine Recommendations

Healthcare providers, including home care (TIV only)

Employees of long-term care facilities (TIV only)

Household members of high-risk persons including children 0-23 months (TIV or LAIV*)

*household and other close contacts of immuno- suppressed persons should not receive LAIV

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Influenza Vaccine Recommendations*

Providers of essential community services Foreign travelers Students Anyone who wishes to reduce the

likelihood of becoming ill from influenza

*these groups may receive TIV, and some may be eligible for LAIV

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Influenza Vaccination of Children

Children <24 months at increased risk of hospitalization

Inactivated influenza vaccination of healthy children 6-23 months is recommended

Vaccination of household contacts and out-of-home caretakers is encouraged

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In the 2001 National Health Interview Survey, only 36% of healthcare workers reported receiving influenza vaccine in the previous 12 months.

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Simultaneous Administration of LAIV and Other Vaccines

Inactivated vaccines can be administered either simultaneously or at any time before or after LAIV

Other live vaccines can be administered at the same visit as LAIV

Live vaccines not administered on the same day should be administered >4 weeks apart

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Inactivated Influenza Vaccine Adverse Reactions

Local reactions 15%-20% Fever, malaise not common Allergic reactions rare Neurological very rare

reactions

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Live Attenuated Influenza VaccineAdverse Reactions

Children– no significant increase in URI symptoms, fever, or other systemic

symptoms

– significantly increased risk of asthma or reactive airways disease children 12-59 months of age

Adults– significantly increased rate of cough, runny nose, nasal congestion, sore

throat, and chills reported among vaccine recipients

– no increase in the occurrence of fever

No serious adverse reactions identified

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Inactivated Influenza VaccineContraindications and Precautions

Severe allergic reaction to a vaccine component (e.g., egg) or following a prior dose of vaccine

Moderate or severe acute illness

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Live Attenuated Influenza VaccineContraindications and Precautions

Children <5 years of age* Persons >50 years of age* Persons with underlying medical conditions* Children and adolescents receiving chronic

aspirin therapy*

*These persons should receive inactivated influenza vaccine

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Live Attenuated Influenza VaccineContraindications and Precautions

Immunosuppression from any cause Pregnant women* Severe (anaphylactic) allergy to egg or other

vaccine components History of Guillian-Barré syndrome Moderate or severe acute illness

*These persons should receive inactivated influenza vaccine

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LAIV Storage and Handling

Must be stored at < +5°F (-15°C ) at all times

Do NOT store in a frost-free freezer Store ONLY in a MANUAL defrost

freezer If no manual defrost freezer, must store

LAIV in special freezer box supplied by the manufacturer

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Influenza VaccineMissed Opportunities

Up to 75% of persons at high risk for influenza or who die from pneumonia and influenza may have received care in a physician's office in the previous year.

In one study all non-nursing home persons who died from pneumonia or influenza had at least one medical visit in the previous year.

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Influenza Antiviral Agents* Amantadine and rimantadine

– effective against influenza A only

– approved for treatment and prophylaxis

Zanamivir and oseltamivir– neuraminidase inhibitors

– effective against influenza A and B

– oseltamivir approved for prophylaxis

*see influenza ACIP statement for details

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Haemophilus influenzae type b

Severe bacterial infection, primarily in infants During late 19th century believed to cause

influenza Immunology and microbiology clarified in

1930s

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Haemophilus influenzae

Aerobic gram-negative bacteria Polysaccharide capsule Six different serotypes (a-f) of polysaccharide

capsule 95% of invasive disease caused

by type b

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Haemophilus influenzae type bPathogenesis

Organism colonizes nasopharynx In some persons organism invades

bloodstream and cause infection at distant site Antecedent URI may be a contributing factor

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Haemophilus influenzae type b Meningitis

Accounted for approximately 50%-65% of cases

Hearing impairment or neurologic sequelae in 15%-30%

Case fatality rate 2%-5% in spite of effective antimicrobial therapy

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Haemophilus influenzae type b Medical Management

Treatment with an effective 3rd generation cephalosporin, or chloramphenicol plus ampicillin

Ampicillin-resistant strains now common throughout the United States

Hospitalization required

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Haemophilus influenzae type b Epidemiology

Reservoir Human Asymptomatic carriers

Transmission Respiratory droplets

Temporal pattern Peaks in Sept-Dec and March-May

Communicability Generally limited buthigher in somecircumstances

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Haemophilus influenzae type bPolysaccharide Vaccine

Available 1985-1988 Not effective in children

<18 months of age Effectiveness in older children variable

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Polysaccharide Vaccines

Age-related immune response Not consistently immunogenic in children ≤2

years old No booster response Antibody with less functional activity

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Polysaccharide Conjugate Vaccines

Stimulates T-dependent immunity Enhanced antibody production, especially in

young children Repeat doses elicit booster response Antibody is biologically active in vitro

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HbOC Hibtiter

PRP-T ActHIB, TriHIBit

PRP-OMP PedvaxHIB, COMVAX

Conjugate Hib Vaccines

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Vaccine 2 mo 4 mo 6 mo 12-18 mo

HbOC x x x x

PRP-T x x x x

PRP-OMP x x x

Haemophilus influenzae type b VaccineRoutine Schedule

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Vaccination at <6 weeks of age may induce immunologic tolerance to Hib antigen

Minimum age 6 weeks Minimum interval 4 weeks for primary series

doses

Haemophilus influenzae type b Vaccine

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Haemophilus influenzae type b VaccineUse in Older Children and Adults

Generally not recommended for persons >59 months of age

Consider for high-risk persons: asplenia, immunodeficiency, HIV infection

One pediatric dose of any conjugate vaccine

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Swelling, redness, and/or pain in 5%-30% of recipients

Systemic reactions infrequent Serious adverse reactions rare

Haemophilus influenzae type b Vaccine

Adverse Reactions

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Haemophilus influenzae type b Vaccine Contraindications and Precautions

Severe allergic reaction to vaccine component or following prior dose

Moderate or severe acute illness Age <6 weeks

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Streptococcus pneumoniae Gram-positive bacteria 90 known serotypes Polysaccharide capsule important virulence

factor Type-specific antibody is protective

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Pneumococcal Disease

Most common cause of vaccine- preventable death

Most common cause of bacterial meningitis among infants and young children

Increasing antibiotic resistance

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Pneumococcal DiseaseClinical Syndromes

Pneumonia Bacteremia Meningitis

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Pneumococcal PneumoniaClinical Features

Abrupt onset Fever Shaking chills Productive cough Pleuritic chest pain Dyspnea, tachypnea, hypoxia

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Pneumococcal Pneumonia Estimated 175,000 hospitalized cases per

year Up to 36% of adult community-acquired

pneumonia and 50% of hospital-acquired pneumonia

Common bacterial complication of influenza and measles

Case-fatality rate 5%-7%, higher in elderly

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Pneumococcal Bacteremia

More than 50,000 cases per year in the United States

Rates higher among elderly and very young infants

Case fatality rate ~20%; up to 60% among the elderly

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Pneumococcal Meningitis

Estimated 3,000 - 6,000 cases per year in the United States

Case-fatality rate ~30%, up to 80% in the elderly

Neurologic sequelae common among survivors

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Pneumococcal Disease in Children

Bacteremia without known site of infection most common clinical presentation

S. pneumoniae leading cause of bacterial meningitis among children <5 years of age

Common cause of acute otitis media

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Pneumococcal Disease Epidemiology

Reservoir Human carriers

Transmission Respiratory Autoinoculation

Temporal pattern Winter–early spring

Communicability Unknown Probably as long as organism in respiratory secretions

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Pneumococcal Vaccines

1977 14-valent polysaccharide vaccine licensed

1983 23-valent polysaccharide vaccine licensed

2000 7-valent polysaccharide conjugate vaccine licensed

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Pneumococcal Polysaccharide Vaccine

Purified capsular polysaccharide antigen from 23 types of pneumococcus

Account for 88% of bacteremic pneumococcal disease

Cross-react with types causing additional 8% of disease

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Pneumococcal Conjugate Vaccine

Pneumococcal polysaccharide conjugated to nontoxic diphtheria toxin (7 serotypes)

Vaccine serotypes account for 86% of bacteremia and 83% of meningitis among children <6 years

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Pneumococcal Polysaccharide Vaccine

Purified pneumococcal polysaccharide (23 types)

Not effective in children <2 years 60%-70% against invasive disease Less effective in preventing pneumococcal

pneumonia

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Highly immunogenic in infants and young children, including those with high-risk medical conditions

>90% effective against invasive disease Less effective against pneumonia and acute

otitis media

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Pneumococcal Polysaccharide Vaccine Recommendations

Adults >65 years of age Persons >2 years with

– chronic illness

– anatomic or functional asplenia

– immunocompromised (disease, chemotherapy, steroids)

– HIV infection

– environments or settings with increased risk

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Routine vaccination of children age <24 months and children 24-59 months with high-risk medical conditions

Doses at 2, 4, 6, months, booster dose at 12-15 months

Unvaccinated children >7 months require fewer doses

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Pneumococcal Polysaccharide Vaccine Revaccination

Routine revaccination of immunocompetent persons is not recommended

Revaccination recommended for persons age >2 years at highest risk of serious pneumococcal infection

Single revaccination dose >5 years after first dose

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Pneumococcal Polysaccharide VaccineCandidates for Revaccination

Persons >2 years of age with:– Functional or anatomic asplenia

– Immunosuppression

– Transplant

– Chronic renal failure

– Nephrotic syndrome

Persons vaccinated at <65 years of age

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Pneumococcal Vaccines Adverse Reactions

Local reactions– polysaccharide 30%-50%

– conjugate 10%-20%

Fever, myalgia– polysaccharide <1%

– conjugate 15%-24%

Severe adverse reactions rare

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Pneumococcal VaccinesContraindications and Precautions

Severe allergic reaction to vaccine component or following prior dose of vaccine

Moderate or severe acute illness

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Rabies. Management and Prevention

Pre-exposure prophylaxis - Inactivated rabies vaccine may be administered to persons at increased risk of being exposed to rabies e.g. vets, animal handlers, laboratory workers etc.

Post-exposure prophylaxis - In cases of animal bites, dogs and cats in a rabies endemic area should be held for 10 days for observation. If signs develop, they should be killed and their tissue.

Wild animals are not observed but if captured, the animal should be killed and examined. The essential components of postexposure prophylaxis are the local treatment of wounds and active and passive immunization.

Once rabies is established, there is nothing much that could be done except intensive supportive care. To date, only 2 persons with proven rabies have survived.

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Postexposure Prophylaxis Wound treatment - surgical debridement should be carried out.

Experimentally, the incidence of rabies in animals can be reduced by local treatment alone.

Passive immunization - human rabies immunoglobulin around the area of the wound; to be supplemented with an i.m. dose to confer short term protection.

Active immunization - the human diploid cell vaccine is the best preparation available. The vaccine is usually administered into the deltoid region, and 5 doses are usually given.

There is convincing evidence that combined treatment with rabies immunoglobulin and active immunization is much more effective than active immunization alone. Equine rabies immunoglobulin (ERIG) is available in many countries and is considerably cheaper than HRIG.

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Rabies VaccinesThe vaccines which are available for humans are present are inactivated whole virus vaccines.

– Nervous Tissue Preparation e.g. Semple Vaccine - associated with the rare complication of demyelinating allergic encephalitis.

– Duck Embryo Vaccine - this vaccine strain is grown in embryonated duck eggs This vaccine has a lower risk of allergic encephalitis but is considerably less immunogenic.

– Human Diploid Cell Vaccine (HDCV) - this is currently the best vaccine available with an efficacy rate of nearly 100% and rarely any severe reactions. However it is very expensive.

– Other Cell culture Vaccines - because of the expense of HDCV, other cell culture vaccines are being developed for developing countries. However recent data suggests that a much reduced dose of HDCV given intradermally may be just be effective.

Health & Medicine

Vaccine4 influenza