112/04/21 1

Vaccines: conquering untreatable

diseases

主講人：王森德 醫師北醫附設醫院健康管理中心主任

北醫附設醫院家醫科主治醫師

(BMJ) Medical Milestones

BMJ 2007;334 Suppl 1:s19.

大綱

BMJ Perspectives

Practical Management of Vaccines- The Canadian Pharmacists Association

Ethic Viewpoints

Economic Value of Vaccines

Vaccination in Taiwan

BMJ Perspectives

Louis Pasteur’s 1885 breakthrough

Rabies vaccine- a laboratory attenuated live virus

1. Laboratory modification of micro-organisms by attenuation less pathogenic but still immunogenic

2. The world’s first medical breakthrough to be recognized and celebrated in the public domain

3. Establish the world’s first purpose built medical research institute- the Pasteur Institute in Paris

(then Robert Koch Institute in Berlin in 1891 the

Lister Institute in London in 1893)

BMJ 2007;334 Suppl 1:s19.

Edward Jenner (a country doctor in Gloucester Shire)- milkmaid and cow

Introduction of vaccination against smallpox in 1796

Observation: Milkmaids who had suffered from cowpox (i.e. vaccinia) were subsequently immune to the deadly smallpox.

Trial: He tried and then promoted inoculation with small doses of vaccnia pustules as a preventive measure- terming the inoculation “vaccine.” save many thousands of lives

Influence: It attracted much scepticism. -Jenner’s innovation was a one-off, and subsequent

attempts at emulation (e.g. syphilis) failed.

BMJ 2007;334 Suppl 1:s19.

Pasteur’s achievements- dogs and children

From vaccines for anthrax, sheep pox, and rabies in animals to those for human diseases.

In October 1885, two children who were savagely bitten by rabid dogs and faced certain death were treated successfully in his clinic.

Pasteur’s coworks developed antitoxic sera for diphtheria and tetanus. cure untreatable Diseases

also prevent killer diseases: protective vaccines using inactivated micro-organisms: cholera, typhoid fever, and the plague

BMJ 2007;334 Suppl 1:s19.

Development of vaccines in the 20th century

Small pox- eradicated in the 1970s through vaccines campaigns

Diphtheria in the UK- 40000~70000 cases each year from 1920 to 1940 around 10 a year by the 1990s

Polio in the UK- 7500 cases each year in the 1950s only 25 in the whole of the 1980s

Tuberculosis- The incidence was reduced largely by the BCG vaccination, introduced in 1927.

BMJ 2007;334 Suppl 1:s19.

New delivery systems and new targets

How would all current vaccines be made available in all countries and all groups across the world? by new delivery systems- aerosols and skin patches- and by the move away from vaccines that need cold storage.

Molecular biology look forward to preventive and therapeutic vaccines for: (1) common infections (e.g. staphylococci and pneumococci), (2) parasitic diseases (e.g. malaria and schistosomiasis), (3) recent infections (e.g. HIV, viral hemorrhagic fever, and severe acute respiratory syndrome), (4) autoimmune diseases, (5) infective cancers (e.g. vaccine against HPV and thus against cervical cancer)

BMJ 2007;334 Suppl 1:s19.

Although Pasteur brought the great benefits of medical innovation to the public’s attention and pioneered the institutionalization of medical research, it is because of the present and future potential for vaccines to save lives and prevent suffering that we can consider his 1885 discovery to be the greatest medical milestone.

By “Michael Worboys”

Rotavirus vaccine

HIV vaccineGene vaccine

BMJ 2007;334 Suppl 1:s19.

Practical Management of Vaccines- The Canadian Pharmacists Association

Vaccines — one of the greatest medical advances of modern times

Vaccination is the best protective strategy.

Vaccine programs are among the most cost-effective public health interventions available.

Protection of individuals and population (herd immunity).

Recent examples in Japan and Ireland show that vaccine-preventable diseases, such as pertussis (whooping cough) and measles, will return when the level of vaccination drops.

the Canadian Pharmacists association May/June 2007

Vaccination in Canada, 1798–1978Small pox- Edward Jenner’s cowpox vaccine in 1796

The last case occurred in Toronto in 1962.

Diphtheria- The discovery of an antitoxin to treat diphtheria outbreaks in the 1890s (France) The 1943 discovery that the pertussis vaccine was an adjuvant to diphtheria toxoid led to the creation of polyvalent childhood vaccines.

Influenza- Not until 1933, when the viral origin of influenza was revealed, would an effective vaccine be possible.

Poliomyelitis- In 1953, Canada experienced its worst polio epidemic, with 8000 cases and 481 deaths. Salk vaccine began in 1955. the addition of the Sabin oral polio vaccine, Polio was eradicated in Canada

Vaccine controversies - 1

Do vaccines ever cause autism? (MMR; thimerosal ((硫柳汞 ))- a mercury-containing compound as a preservative used in multi-dose vials of vaccines)

Do vaccines ever cause other serious adverse events? (1) Anaphylaxis VS any vaccine. (2) MMR VS thrombocytopenia or encephalitis. (3) influenza vaccine VS Guillain-Barre syndrome. (4) The incidence of these adverse events VS infection with these viruses. (5) currently no convincing evidence that there is a link between immunizations and long-term sequelae such as cancer, multiple sclerosis, diabetes mellitus or autoimmune diseases.

Emerg Infect Dis 2006;1880-7.

Vaccine controversies - 2Children now routinely receive 3 immunizations

containing up to 7 vaccines at a time. Will multiple vaccines overload the immune system? In fact, the number of antigens presented to the immune system is actually much lower now than it was in the past.

What is the link between increased immunizations and the rising incidence of allergic disorders and asthma? It seems unlikely that preventing this small percentage of the viruses and bacteria that children encounter increases the incidence of Th2 dominant reactions, and there is evidence that the increase in the incidence of asthma preceded the marked increase in the number of immunizations.*

Pediatrics 2007;119:222-3.

What will the role of immunization be during a pandemic? (e.g. Influenza)

A pandemic is an epidemic that occurs over a wide geographic area.

There is no doubt that the most successful public health strategy to prevent the spread of this virus will be widespread immunization with an effective vaccine.

However, it currently takes about 6 months to develop influenza vaccines once new human strains of the virus are identified, and it is less certain an effective vaccine can be made within this time frame for avian strains.

Newer methods of making influenza vaccines in shorter periods of time are being developed.

Adult vaccination: Missed opportunitiesor opportunity not to be missed?

The burden of many infectious diseases has shifted to the adult population.

The preventable diseases are often more severe in adults, but also secondary effects of illness in vulnerable populations such as children, pregnant women and the elderly.

Pertussis The proportion of pertussis in the adult population has increased from 6% to more than 18% since 1988, and adults have been found to be the primary source of pertussis in two-thirds of infant cases.*

Pediatr Infect Dis J 1998;17:412-18.

Adult vaccination: Missed opportunitiesor opportunity not to be missed?

Recommended vaccines for adults in Canada: tetanus, diphtheria, pertussis, measles, mumps, rubella and varicella as a minimum; as well, influenza and pneumococcal immunization is recommended.

Surveys have shown that almost 50% of adults in Canada do not have adequate coverage for tetanus or diphtheria. Only 10 of 74 patients admitted to a tertiary care medical unit for invasive pneumococcal disease had been previously vaccinated.

Ethic Viewpoints

CPJ/RPC. May/June 2007. VOL 140 [ suppl 2 ]

CPJ/RPC. May/June 2007. VOL 140 [ suppl 2 ]

The debate on MMR vaccine

Around 2000, a debate on whether it was adequately safe to vaccinate children with the measles, mumps and rubella (MMR) vaccine was raised in Northern Europe and the US.

Against: Wakefield et al. suggesting a causal, sequential relationship between the MMR vaccine and a novel syndrome that included chronic inflammatory intestinal diseases and autism.

For: Many researchers argued that Wakefield’s study design and sample size were inadequate. In addition, they argued that the damage caused by naturally contracting such infectious diseases was greater than the adverse events that caused by vaccine.

Lancet 1998;351:637-41.

Two-side Effects of VaccinesAdvantages of vaccines- preventing the occurrence

of infectious diseases: e.g. (1) Eradication of small pox by cowpox vaccine. (2) Poliomyelitis nearly disappeared worldwide by preventive vaccination. (3) The dissolution of the Soviet Union (1990s) caused the collapse of their public health system, resulting in a massive outbreak of diphtheria*.

Disadvantages of vaccines- adverse events caused by vaccination: e.g. (1) oral poliovirus vaccine VS vaccine-associated paralytic poliomyelitis (VAPP), (2) measles vaccine VS acuter encephalitis, (3) yellow fever virus vaccine VS yellow fever, (4) influenza vaccine VS GB syndrome & anaphylactic shock

Emerg Infect Dis 1998;4:539-50.

Arguments for supporting a compulsory childhood vaccination policy The right of children

The responsibility of parents

The right of communities/Communitarian- The right of the entire community should surpass the rights of individuals. Unless a medical contraindication is present, centralized national power should surmount personal freedom.

Utilitarian/Consequentialist- Utilitarians believe that the nature of an action or policy is based on a balance between the good and bad outcomes. If compulsory vaccination policy is the best way to protect children and is accepted by the community, it is usually supported by utilitarians.

Journal of Pediatrics & Child Health 2004;40(7):392-6.

Arguments for opposing a compulsory childhood vaccination policy

The rights of parents- Families and parents need to perform their functions without any disturbance, that is, families are entitled to have privacy.

The respect for parents’ decision-making authority- The respect for other people’s free-to-choose rights is the most fundamental concept among ethicists.

Variable advantages and disadvantages for different vaccines- Vaccines against communicable diseases VS the tetanus vaccination (herd immunity VS individual protection)

The trust and the autarchy (信任 VS專制 )- Compulsory vaccination policy provokes people who believe that the government has already intervened too much in their freedoms.

Journal of Pediatrics & Child Health 2004;40(7):392-6.

Economic Value of Vaccines

Economic Value of Vaccines

In general, immunization programs are among the best investments in health.

Globally, the effectiveness and low cost of vaccines (relative to the cost of disease treatment and long‐term care) have made immunization programs essential to maintaining public health.

Cost-Savings

20 reviews of economic evaluation studies for universal childhood vaccination strategies, 70% of these studies demonstrated cost‐saving results from the perspective of society, compared to no vaccination.*

Every dollar invested in childhood vaccination against nine vaccine‐preventable diseases (diphtheria, tetanus, pertussis, Haemophilus influenzae type b, polio, measles, mumps, rubella, and hepatitis B) the benefit-cost ratios for these vaccines are in the range of 5:1 for direct costs and 17:1 for societal costs (indirect costs included).**

* Vaccine 22 (2004), p1992–2005.

** Pediatric Research 53, No. 4 (2003): 206A

Benefit Cost Ratio(BCR)(效益成本比 )

BCR = Benefit / Cost。 BCR > 1表示獲利大於成本。

Cost-Effectiveness

Prior to 2000 most of vaccines were cost‐saving – for every dollar spent on vaccination, more than one dollar was saved in medical or societal costs.

In 2000 and thereafter Vaccines have typically not been cost‐saving, but cost-effective. Most vaccine economic analyses have measured costs‐effectiveness in terms of dollars per life year saved or per disease case prevented.

However, comparisons of dollars per life year saved may still underestimate the economic value of vaccines, since these analyses do not give credit for averting pain, suffering, or disability attributable to disease.

Incremental cost-effectiveness ratio (ICER), ICER=ΔC/ΔE=[(C1-C2)/(E1-E2)]

Quality‐adjusted life years (QALYs) & Disability‐adjusted life years (DALYs)

Economic analyses should give vaccines credit for preventing disease and disability by using quality‐adjusted life years (QALYs) saved or disability‐adjusted life years (DALYs) averted.

QALYs are often used as the standard for economic analyses in North America, whereas DALYs are more commonly used for international or cross cultural comparisons.*

Potential benchmarks suggested: $50,000 or $100,000 per QALY saved or 1‐3 times the countryʹs gross domestic product (GDP) per capita per DALY averted. e.g. vaccination with Gardasil of 12‐year‐old girls cost the health provider $Cdn 21,000 per QALY‐gained.

Health Affairs, 2005, Vol. 24. No. 3, p666‐678.

The extra life-years are given a value between 0 and 1 to account for the degree of health.

Numbers needed to vaccinate (NNV)

EXAMPLE ：“ numbers needed to vaccinate” (NNV) to prevent HPV‐related diseases and death among 12-year-old girl.

(1) NNV is defined as the number of women (within a specific age cohort) who would need to be vaccinated to prevent a single HPV‐related event during their lifetime

(2) NNV to prevent death from cervical cancer: 729

(3) NNV to prevent one life year lost: 16

Comparative data for vaccines against varicella, meningococcal and influenza: NNV values to prevent one death from each of these diseases: 34,000, 21,000 and 5,000 respectively.

Additional Economic Benefits

“Herd immunity”- vaccines uniquely offer additional value in terms of the public good.

Vaccination programs serve to draw patients into health care facilities, where patients receive other recommended (and often cost‐effective) preventive services.

Many kinds of vaccines have documented reductions in hospitalization due to relative infections. This clearly indicates the potential for vaccines to ultimately reduce hospital expenditures.

Additional Economic Benefits

Vaccination can positively affect worker productivity by reducing absenteeism in the workplace. (indirect costs)

(e.g. Influenza vaccination could prevent 49 cases of influenza per 1000 workers vaccinated, avoiding 93 lost workdays, or 0.09 days per employee, at a net cost of approximately $US 3 per employee vaccinated.)

Vaccines for emerging disease- Infectious diseases ( e.g. severe acute respiratory syndrome (SARS), the West Nile virus, and the threat of pandemic influenza) & non‐infectious diseases (such as cancer, and neurological disorders, e.g. Alzheimer’s disease ),

American Journal of Medicine (2005) 118, p68‐77.

Vaccination in Taiwan

http://web.cdc.gov.tw/public/Attachment/1719543440.pdf

Children receiving polio vaccination, 1955.

Private collection of Dr. Heather MacDougall.

CPJ/RPC. May/June 2007. VO L 140 [ suppl 2 ]

http://web.cdc.gov.tw/public/Attachment/17110521242.pdf

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