Updates By Carol A. Kemper, MD, FACP
Updates
By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
It's the Flu Season!
Source: Brewer NT and Hallman WK. Subjective and objective risk as predictors of influenza vaccination during the vaccine shortage of 2004-2005. CID. 2006;43:1379-1386.
Within the United States, 3 groups of individuals have been deemed the highest priority for annual influenza vaccination based on estimates of risk: (1) Persons ≥ 65 yrs; (2) Persons 18-64 yrs with chronic health conditions such as cardiorespiratory disease or who reside in a long-term care facility; (3) and health care workers and other persons with close contact with groups 1 and 2. Despite heavy promotion of this national priority, the CDC estimates vaccine coverage during the 2004-2005 influenza season (during the flu vaccine shortage) at 60% for elderly adults, 26% for persons < 65 yrs at high risk, and 36% for HCWs and those with close contact with groups 1 and 2.
If you think these 3 groups are hard to remember, imagine how difficult it might be for someone age 58 with hypertension to figure it out — are they at high risk or not? This study suggests that patients have a poor understanding of their objective risk for influenza and its complications (half of those at high risk had no perception they were), and the decision to seek influenza vaccination is based on other more subjective perceptions of risk. Since many persons elect to pursue vaccination on their own and not necessarily at the suggestion of a physician (eg, drive by clinics, drug store promotions), self-perceptions of risk are paramount to the process.
In this study, rates of vaccine coverage were significantly greater for individuals at high objective risk compared with those who were not (36% vs 6%, respectively). However, a much-more significant predictor of vaccination was an individual's perceived subjective risk (64% vs 7%, respectively). Less significant factors included physician recommendation, prior vaccination, and neuroticism. In addition, for unvaccinated persons at either high or low objective risk, the most common reason provided for skipping vaccination was the vaccine shortage (37% vs 20%, respectively). Thus, patient perception of relative need was modulated by the announcement of limitations in vaccine supply.
These authors suggest that amending the high risk criteria to something clear and unambiguous, such as age, may help promote vaccine coverage, especially amongst the elderly. Announcements regarding limitations in vaccine supply only serve to discourage those in need from getting vaccinated.
Avian Flu — Not a Pandemic Threat?
Source: Maines TR, et al. Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. The Proceedings of the National Academy of Science (PNAS). 2006;103 (32) ; 12121-12126.
Avian Influenza H5NI has resulted in more than 200 cases of human infection in 10 countries, with an estimated 50-60% mortality rate. Most of these cases are the result of transmission from infected poultry directly to humans. While human to human transmission has probably occurred in a couple of cases with close contact, the virus has not yet acquired the ability for efficient transmission in humans, a necessary step in virus evolution for pandemic flu. Both the 1957 and 1968 pandemic flu's were due to gene reassortments between avian and human influenza virus, such that the more virulent avian influenza virus acquired human virus-like receptor proteins, allowing it to be readily passed from human to human.
Researchers at the CDC have shown that much more than gene reasortment is required to create an avian influenza virus that is both virulent and transmissible in humans, although what that missing link might be is not understood. Using a ferret model, scientists assessed the virulence and transmissibility of various avian-human influenza virus combinations. Ferrets were selected because they are similar to humans in their vulnerability and respiratory transmission of influenza virus. In addition, like people, they can be infected by avian flu virus but do not readily transmit it. In this model, virus recreated with human influenza A H3N2 virus surface proteins and 1997 avian influenza A H5N1 internal protein genes demonstrated efficient replication but poor transmission. Conversely, various gene reassortments with H5N1 with 4 to 6 human influenza virus internal protein genes demonstrated reduced replicative capacity and no transmission. Even serial passages of re-created virus failed to enhance transmissibility. Interestingly, the recombinant viruses did not cause as severe in illness in the ferrets as the original H5N1 virus.
These data demonstrate that some unknown factor beyond a combination of human influenza surface proteins and avian virus internal machinery is necessary to create a flu bug with pandemic potential.
Darwin and the Flu
Source: Wolf Y, et al. Long intervals of stasis punctuated by bursts of positive selection in the seasonal evolution of influenza A virus. Biology Direct. 2006;1:34.
A popular theory holds that human influenza virus is constantly evolving with seasonal changes in hemagglutinin (HA) surface proteins in a continuing effort by the virus to outsmart the human immune system response and find a new environmental niche. Very different findings were reported by researchers at the NIH who examined a large collection of H3N2 and H1N1 virus, the two most common human influenza strains in circulation during the past 10 years. More than 1,000 strains of virus from flu seasons in New York State and New Zealand were examined.
Rather than a more gradual Darwinian process as previously imagined, examination of the H3N2 virus HA gene found relatively long periods of stability in the HA gene sequence of severa co-circulating viruses, all of which appeared to have similar genetic fitness and virulence. These stable intervals were then punctuated by the sudden appearance of a new virus with rapid escalation in genetic fitness, which quickly becomes the dominant strain, displacing earlier strains.
Researchers found that these longer intervals of stability in the HA gene were characterized by neutral gene sequences with a uniform distribution of synonymous amino acid substitutions sprinkled across the epitome region. In contrast, more rapid shifts in selection of a newer dominant strain were characterized by an excess of amino acid substitutions in one location of the epitome region. The same amino acid substitutions occurred independently in H3N2 virus of different lineages, providing an explanation as to why the sudden appearance of a new strain seems to eclipse all previous strains. Interestingly, no single subset of amino acid substitutions resulted in a corresponding or predictable fitness increase, but rather a single and final amino acid change suddenly vaulted the virus to the top.
During the 10-year period examined, no significant shift in the H1N1 HA gene was observed. Thus, it appears that the intermittent appearance of the H1N1 as the more dominant circulating strain is likely due to the diminished fitness of, and reduced susceptibility to, circulating H3N2 strains, leaving a transient environment niche. It would be useful to better understand the selective pressures that drive these antigenic changes in the HA gene and sudden shifts in dominant virus.
Seroprotection of Rabies Vaccine In Travelers
Source: Ranney M, et al. Rabies antibody seroprotection rates among travelers in Nepal: "Rabies seroprotection in travelers." J Travel Med. 2006;13 6); 329-333.
With the increase in international and adventure travel, especially to parts of Asia, exposure to rabies is increasingly of concern. More than 20,000 cases of rabies occur annually in India, and China just announced a one dog per household policy to curb the spread of rabies in that country.
The adequacy of pre-existing rabies seroprotection in vaccinated travelers to Nepal was examined in a prospective convenience sample. Serum samples from 43 persons (aged 19-60 years) who reported prior rabies vaccination (range, 1 month to 6 years) were examined for the presence of seroprotective antibody titers (defined as ≥ 0.5 IU/mL). Data on the type and number of vaccinations, and the route of administration was available for 38 persons. Of these, 66% had received purified Vero cell rabies vaccine (PVRV) and 34% received human diploid cell vaccine (HDCV). Intradermal vs intramuscular administration of vaccine was reported in 26% and 74%, respectively. The majority had received their vaccine in Europe, although a few had received it in Asia. Seven subjects received ≥ 3 doses of vaccine for post-exposure prophylaxis, 29 received ≥ 3 doses of vaccine for pre-exposure prophylaxis, and 2 received 2 doses.
There was no association between low titers and the type of vaccine administered, the route of administration, the number of vaccines, the time elapsed since vaccination, or age. One person had antibody titers below the cut-off, and 2 had serum titers near the cut-off (0.5-1.5 IU/ml). These 3 individuals received their vaccine an average of 10 months earlier compared with 18 months for the rest of the group. The first individual received 3 doses of intradermal HDCV, which should have been adequate. An interesting question not addressed in this study was whether persons with low or inadequate titers would respond to a booster dose of vaccine. Most individuals with prior rabies vaccination within 6 years demonstrate protective levels of antibody.
Within the United States, 3 groups of individuals have been deemed the highest priority for annual influenza vaccination based on estimates of risk: (1) Persons ¡Ý 65 yrs; (2) Persons 18-64 yrs with chronic health conditions such as cardiorespiratory disease or who reside in a long-term care facility; (3) and health care workers and other persons with close contact with groups 1 and 2.Subscribe Now for Access
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