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• An Avian Influenza Vaccine?
• Influenza and Pneumococcal Vaccinations
• Pertussis Booster Vaccine
• Pertussis Update
• Vaccine Against Herpes Zoster Virus (HZV or Shingles)
• Vaccine Update

An Avian Influenza Vaccine?

When the H5N1 avian influenza virus re-emerged in Hong Kong in 2003, it triggered a pandemic alert by the World Health Organization (WHO). The newer strains of the virus seem to have a greater pathogenic capacity in animals than did earlier strains. According to WHO, the virus has infected at least 275 people in 10 countries and killed at least 167. While the lethal virus has not yet appeared in the United States, U.S. Health Agencies are rapidly revamping disaster plans to include a coordinated national, state, and local community response to a respiratory pandemic.

One avenue of preparedness lies in the development of a safe and effective vaccine. Recombinant re-assortment technology is being used to prepare vaccines against H5N1 avian influenza strains and clinical trials have been, or are being, conducted at various facilities around the world.

The WHO Global Influenza Programme Network continues to monitor the antigenic and genetic evolution of circulating H5N1 viruses and is working to develop vaccines against these various strains. See www.who.int/csr/disease/avian_influenza/. A pre-pandemic candidate vaccine, (developed by WHO at the Centers for Disease Control and Prevention (CDC) in Atlanta and the China Centers for Disease Control in Beijing), using a new recombinant H5N1 virus from A/Anhui/1/2005 selected from clade 2, sub-clade 3, is available from WHO under a Material Transfer Agreement (MTA).

The March 2006 issue of The New England Journal of Medicine contained a study on a pandemic vaccine by Sanofi-Aventis that showed protective immune response initiation in 45% of healthy people who received the highest dose. A January 2007 meeting of the FDA failed to approve the vaccine. The FDA has approved a "Fast Track" for approval of new vaccines and drugs should the need arise. If approved later, the Sanofi-Aventis vaccine will be the first of its kind on the U.S. market.

However, it remains unclear if these vaccines will be truly effective against the avian influenza organism if it mutates into a strain with more efficient transmissibility from human to human AND maintains its current mortality rate of about 50%.

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Influenza and Pneumococcal Vaccinations

Vaccination Statistics:

• In the United States, influenza and pneumococcal infections are responsible for causing the largest number of vaccine preventable deaths.
• Ninety-percent of these deaths are in the elderly population.
• Vaccines are under-utilized in spite of being safe, cost effective and clinically effective.
• Flu vaccine is safe, 40%-50% effective in preventing hospitalization, and 80% effective in preventing death.
• Pneumococcal vaccination is 75% effective in preventing invasive disease (bacteremia).

Acute Care:

• Billing records show that very few patients admitted to the hospital with a high risk diagnosis are given immunization during their hospital stay.
• Forty-nine percent of those who die of pneumococcal disease had been hospitalized in the previous three to five years.
• Computer assisted prompts reminding the doctor to order vaccines improve infection rates.
• Automatic process: Place a field on the face sheet for vaccination. If no vaccination, the nurse completes an assessment. If no restrictions, the pharmacy writes a prescription. The nurse gives the vaccination.

Long Term Care:

• Those facilities that implement standing orders for vaccination have much higher rates of vaccination than those facilities that require individual doctor's orders.
• Medicare does not require individual doctor's orders for influenza or pneumococcal vaccinations.
• Residents that receive both vaccinations have a 30% decrease in mortality.
• As of 2005, the MDS will have a field for vaccination. The pneumococcal vaccination rates will be a quality indicator.
• ACIP recommends vaccination if the history of pneumococcal vaccination is unknown. In the future there may be a vaccination registry.
• The myth that it is unsafe to immunize the immunosuppressed patient is untrue...it is recommended.
• There is liability in not vaccinating because it is becoming the standard of care.

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Pertussis Booster Vaccine

Another vaccine may be recommended for health care workers to protect them against the increasing risk of pertussis. This infection known as "whooping cough" is especially dangerous for infants. The FDA is expected to approve two new pertussis vaccines in the next year. There will be a vaccine for adolescents and another for adolescents and adults. The booster vaccine contains three antigens of pertussis and will be combined with diphtheria and tetanus boosters.

The numbers of pertussis cases have been increasing due to waning immunity in adolescents and adults. Infants are at greatest risk. Infants two months old and younger can't receive the vaccine and account for the greatest number of deaths from this infection. Pertussis is transmitted by aerosolized respiratory droplets and is highly communicable during the catarrhal stage and first three weeks after cough onset.

The standard for laboratory diagnostic testing is to isolate Bordetella pertussis by culture. Testing after antibiotics or beyond the first three weeks of illness reduces the success of isolating the organism. PCR testing and enzyme-linked immunosorbent assay for antipertussis toxin IgG are not yet nationally validated or standardized.

Clinical presentation begins with a 7-10 day incubation followed by a 1-2 week catarrhal stage with symptoms of coryza, mild fever and mild cough. The next stage presents with a paroxysmal cough lasting for 1-6 weeks followed by the convalescent stage as the cough lessens over a greater than three week period.

The preferred treatment is with macrolides (erythromycin, azithromycin or clarithromycin) but trimethoprim- sulfamethoxazole is an alternate for those patients who can't tolerate macrolides. There is currently a vaccine for prevention available for children in a five dose series. Healthcare workers with pertussis-like symptoms should be tested and treated. Employees with pertussis should be excluded from work until five days after antibiotic treatment is initiated. If no antibiotic treatment is given, the employee should be excluded from work for 21 days after the onset of symptoms. Droplet precautions are used for patients with pertussis infection. Patients are separated from others by three feet and surgical masks are worn by care providers of these patients.

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Pertussis Update

The year 2006 marks the 100-year anniversary of the discovery that the bacterium Bordetella pertussis is the causative agent of whooping cough. In the early- to mid-1900's, pertussis was one of the most common childhood diseases and a major cause of childhood mortality in the United States.

After the introduction of pertussis vaccine in the 1940s, pertussis cases decreased from the average incidence of 150/100,000 to only 1/100,000 of the US population in 1980. However, since the 1980s, the number of cases has been steadily climbing. The pertussis vaccine is far from perfect and cases have been appearing in fully immunized children and adults.

Cases among adults are particularly problematic as the presentation is atypical, with the patient having little more than a chronic cough. Infected adolescents and adults may introduce pertussis into households where susceptible preschool-age children could be exposed.

Laboratory Diagnosis

The diagnosis of pertussis is usually based on a characteristic history and physical examination. However, laboratory tests may be useful with young infants, atypical cases and cases modified by vaccine or previous antibiotic therapy. B. pertussis specifically binds to ciliated epithelial cells. Since the nasopharynx is lined with ciliated epithelial cells, culture of this site has a higher yield than culture from any other specimen source. However, culture is slow; it may take as long as 10 days to isolate this organism. Therefore, it is of limited value in an outbreak setting where the organism can be rapidly spread from person to person via inhalation.

Direct fluorescent-antibody (DFA) for B. pertussis yields a quicker response than culture, but it has a sensitivity of only 50 to 65%, and false-positive results occur. Ordering DFA for pertussis is not recommended.

Polymerase Chain Reaction (PCR) has become the method of choice for diagnosing pertussis. This is especially important in settings where specimens may be delayed in transport, because such transport compromises the sensitivity of culture but not the sensitivity of PCR. PCR is rapid (usually less than 48 hours turn-around-time), is far more sensitive than culture, and has a high negative predictive value. False positives may occasionally occur because of cross-reactivity with organisms similar to B. pertussis. In some situations, it is recommended that culture for B. pertussis be performed in addition to PCR so that the organism is available for susceptibility testing and molecular epidemiology studies.

The optimal specimen for pertussis is a nasopharyngeal swab collected during the first two weeks of disease. A separate NP swab should be collected for PCR and culture.

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Vaccine Against Herpes Zoster Virus (HZV or Shingles)

In May 2006, the Food and Drug Administration (FDA) announced it had approved Zostavax [Zoster Vaccine Live (Oka/Merck)] to prevent shingles or reduce the pain associated with shingles in those 60 years and older. The safety and efficacy of a single dose was demonstrated in a landmark clinical trial published in 2005. This trial involved over 38,000 individuals, 60 of which who had never had shingles. While the virus that causes shingles is the same one that causes chickenpox, this new vaccine (Zostavax) is not the same used to prevent chickenpox (Varivax). Zostavax is not recommended for children. It is not indicated for treating either zoster or postherpetic neuralgia, nor is it for those who are immunosuppressed or on immunosuppressive therapy. The duration of protection is also unknown, and it has not been studied in those with a previous history of shingles.

The first infection with the varicella zoster virus (VZV) is commonly called chickenpox and most often affects children under age 12, although it can occur at any age. It is highly communicable via respiratory droplets (e.g. coughing, sneezing) as well as through direct or indirect contact with drainage from the characteristic rash or lesions. The symptoms, while annoying, tend to be mild. Chickenpox generally results in lifelong immunity. However, the virus may remain dormant in the sensory ganglia (a swelling of neurons along the course of a peripheral nerve). In a proportion of older adults, VZV may reactivate from the latent state and cause herpes zoster, also known as shingles. Shingles is not as contagious as chickenpox, and while it also manifests as a rash, the presentation is markedly different. The rash is localized in a unilateral distribution following the line of the affected nerve or dermatome and leads to painful blisters and sores on the skin. It is often associated with severe neuropathic pain, which can last long after the disappearance of the rash. The most common site is a dermatome spanning one side of the trunk around the waistline. However shingles can involve any part of the body. As a person moves past 60 years of age, the chance of reactivating VZV or experiencing intense pain associated with the rash tends to increase.

Herpes Zoster in the older person can be very debilitating and significantly interfere with one's ability to perform the normal activities of daily living. The pain can last for months or even years, and sensitivity can range from mild irritation to exquisite pain. Due to pain, disability, or disfigurement, shingles can result in isolation for those affected. This new vaccine may bring a promise of an extended quality of life and reduce the fear of painful shingles in the most elderly of our population.

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Vaccine Update

July 2007

In 2005 and 2006 five new vaccines were FDA licensed and are now providing protection from serious infections and cervical cancer.

Pertussis: In 2005 Tdap vaccines were approved to provide protection from pertussis as well as tetanus and diphtheria. Both were approved as boosters for those who had already received a complete series of doses of DTaP/DTP. Immunity obtained from childhood vaccination is felt to wane over time. Boostrix (GlaxoSmithKline) was approved for persons age 10-18 years and Adacel (sanofi pasteur) was approved for persons age 11-64 years.

The incidence of reported pertussis cases is increasing. In 2004 25,827 cases were reported in the US and 27% were among adults. The objective of the vaccine is to both protect vaccinated adults and to reduce the reservoir of pertussis in the population. This protection will reduce exposure to infants who are at greatest risk for complications and death.

Rotavirus: In 2006 RotaTeq (Merck) was approved by the FDA as a vaccine to prevent rotavirus gastroenteritis. Rotavirus causes severe diarrhea and is the most serious in babies and young children. It is responsible for up to 70,000 hospital admissions per year in the US resulting in as many as 60 deaths. This is an oral vaccine containing five live reassortant rotaviruses. It is given in three doses at 2, 4, and 6 months of age. About 98% of all children who get the vaccine will be protected from severe diarrhea and 74% will not get rotavirus diarrhea at all.

Human Papillomavirus: Also in 2006 the first vaccine to prevent human papillomavirus was FDA approved under the name Gardasil (Merck). This inactivated vaccine is quadrivalent (types 6/11/16/18). HPV-16 and HPV-18 cause 70% of cervical cancers worldwide. Cervical cancer is the second most common type of cancer in women. HPV-6 and HPV-11 cause 90% of genital warts. The vaccine efficacy is 98% in those not previously exposed to HPV. For those who are already infected with one type of HPV the vaccine can protect against the other three types. The vaccine is recommended for girls 11-12 years of age and also females 13-26 years of age who did not receive it when they were younger. It is a three dose series completed in six months.

Shingles (Herpes Zoster): Zostavax (Merck) was FDA approved in 2006. 25% of all people will develop zoster in their lifetime often leaving them with chronic pain. This vaccine is most effective in people 60-69 years of age. It has been found to prevent shingles 51% of the time and post-herpetic neuralgia 67% of the time. It is recommended for everyone 60 years of age and older including those who have had an episode of shingles. This is a live attenuated vaccine given by injection as a single dose. It is not indicated for treatment of zoster or postherpetic neuralgia.

Meningococcal disease: In 2005 the FDA licenced MCV4-Menactra (sanofi pasteur). Invasive meningococcal disease can cause meningitis, blood stream infections and pneumonia. This bacterial infection affects about 2,600 people in the US annually causing up to 15% of those to die in spite of antibiotic treatment. Complications of these infections can lead to loss of arms and legs, deafness, mental retardation, seizures and stroke. In the US almost all of the infections caused by Neisseria meningitides serogroup B, C and Y. This vaccine protects against A, C, Y and W-135. Type B causes about one third of the infections but there is currently no vaccine to protect against this type.

There are two meningococcal vaccines available in the US. Meningococcal polysaccharide vaccine (MPSV4) has been available since the 1970s. Meningococcal conjugate vaccine (MCV4) was licensed in 2005. Both vaccines protect about 90% of those who receive it but MCV4 is expected to protect better and longer. It is also expected to prevent transmission from person to person. A single dose of MCV4 is recommended for 11-18 year olds preferably before they start high school. It is also recommended for anyone 11-55 years of age who is at risk. MPSV4- (Menomune) can be given to children 2-10 years old and adults over 55 years old who are at risk.

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