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.
Physician Alert—Tamiflu®
Most physicians are aware that Roche withheld the distribution and sales of Tamiflu several weeks ago in order to prevent indiscriminate stock piling of drug badly needed for patients with Influenza A and B this coming winter.
In addition, public health departments are making efforts to reassure clinicians and the public, and strongly discouraging clinicians from prescribing oseltamivir phosphate (Tamiflu®) to patients as a safeguard against public fears of a possible avian influenza ("bird flu") epidemic. They are also strongly discouraging the public from stock piling drug for the personal use. Clinicians are also being discouraged from prescribing Tamiflu to travelers to China and Southeast Asia for self--administration in the event of febrile illness. Individuals traveling to southeast Asia should not attempt to self-administer Tamiflu in the event of a fever without appropriate medical evaluation, especially if there is a suspicion of avian influenza (and should not travel with a fever)!
Reassure your patients with the following information:
- While outbreaks of H5N1 avian influenza continue to occur throughout Southeast Asia and Europe, only a limited number of sporadic human cases and deaths from avian influenza have occurred—virtually all of whom had close contact with infected domestic poultry.
- No sustained transmission of H5N1 avian influenza has occurred in humans;
- No cases of been seen in either poultry or people in the United States;
- The indiscriminate and inappropriate use of Tamiflu could lead to the emergence and spread of influenza virus resistant to this agent, rendering it useless in the event of a true public health emergency;
- At present, the more immediate priority for Tamiflu is for the treatment of people with the regular flu during the upcoming flu season, especially those at greatest risk for complications, such as young children, the chronically ill, and the elderly. Stockpiling drug may limit supplies for people with a real need.
- A limited supply of Tamiflu
- exists. Stockpiling drug for personal continuous use for weeks or even months for "prevention" of infection in the event of a real avian influenza epidemic is simply not feasible.
- The single best way to protect a large population against the possibility of an avian influenza epidemic is the development of an effective vaccine.
The Next Flu Pandemic—In Dogs
New York Times, September 22, 2005.
While attention is focused on the spread of avian influenza across Asia and Europe, another strain of influenza has hit closer to home—and is spreading among dogs. Infections and deaths from canine influenza have been reported in 7 states, including Florida, Massachusetts, Arizona, West Virginia, Wisconsin, Texas, and Iowa. This strain of what is believed to be an original H3N8 equine influenza virus was first detected in January 2004 at a racetrack in Jacksonville, Florida, where 8 of 24 infected greyhounds died. The virus has since quickly spread among dogs in close contact or boarded in close proximity, such as racetracks, dog clubs, kennels, shelters, and pet shops. Kennel workers have carried virus home with them, and some kennels have had to close their doors for up to 3 weeks to disinfect.
Dogs have no pre-existing immunity to this virus, and thus far a vaccine does not exist. About 80% of infected dogs develop a clinical illness, with spiking fever to as high as 106, running nose and sniffles; some develop pneumonia. About 15% require hospitalization, and mortality reportedly varies between 1-10%, and is higher in puppies and older dogs.
While amantadine and oseltamivir are active in vitro against this strain of virus, neither is approved for use in dogs. Supportive care, fluids and antibiotics may decrease mortality; avoiding other ill animals is key.
The Deadliest Influenza Pandemic—1918 Revisited
Sources: The 1918 Flu Virus is Resurrected. Nature. 2005,437:794-795. Erratum in: Nature. 2005;437:940; Ghedin E, et al. Large-Scale Sequencing of Human Influenza Reveals the Dynamic Nature of Viral Genome Evolution. Nature. 2005;437:1162-1166.
Five years ago, British scientists detected RNA fragments of the 1918 Influenza virus in the frozen human remains of several coal miners struck down by the disease and buried in the permafrost in Spitsbergen, Norway more than 80 years ago. It was hoped at the time that if the fragments found in brain tissue could be sequenced and pieced together, they might explain the basis for this organism’s particular virulence.
They struck miner's gold. Researchers at the United States Armed Forces Institute of Pathology, who have spent years painstakingly attempting to sequence these fragments, have reconstructed the entire viral genome, discovering that the 1918 Influenza strain contained elements new to humans at that time. At least 3 pieces of genetic code contained sequences distinct to avian influenza viruses. Mutations within genes that control the efficiency of viral replication within cells were also detected. Based on these investigations, it seems fairly certain that the 1918 Influenza virus was either a large reassortment of human and avian influenza viral genes—or possibly predominately an avian influenza virus that adapted to replicate efficiently in humans. It also appears that the 1957 "Asian flu" and the 1968 "Hong Kong flu" may also have been human influenzae that acquired key genetic sequences from avian influenza viruses.
Miraculously, the 1918 Influenza virus has been "reconstituted" in mice, currently under stringent security at the US Centers for Disease Control and Prevention!
A second group of researchers have also been working with the influenza genome, discovering that influenza virus is a highly dynamic virus, making it an ideal pathogen in humans. These authors have developed methods for large-scale sequencing techniques specifically for the influenza genome. They have publicly made available 209 complete genomes of human influenza A virus, encompassing a total of 2,821,103 nucleotides. This process will make identification of genomic changes in the virus more readily apparent, and the evolution of these viruses can be more efficiently tracked.
Some experts were also hoping that discovery of the genetic origins of the 1918 Influenza virus, which killed an estimated 30 to 50 million people worldwide, might also help to determine whether it was responsible for cases of "encephalitis lethargica" (von Economo’s disease) subsequently linked to cases of post-encephalitic parkinsonism, which occurred at about the same time. An early effort to isolate virus from the brains of patients with encephalitis lethargica was fruitless, suggesting that the encephalitis may have been unrelated to the viral infection, or was a possible consequence of some other post-infectious inflammatory condition, such as Reye's.
Talking Device Promotes Adherence in HIV
Andrade ASA, et al. Clin Infect Dis. 2005;41:875-882.
Adherence and virologic outcomes were measured over a 6-month period in a total of 64 patients, 28 of whom were antiretroviral naïve. The patients were assessed with a battery of neuropsychological tests to assess attention, memory, new learning, psychomotor speed, executive functions, and levels of depression. Patients were randomized to 30-minute monthly adherence interventions provided by a clinical pharmacist, with or without the use of a "disease management assistance system" (DMAS) device. The DMAS device is a battery operated digital signal processor, measuring about the size of a handheld calculator, and has programmable voice signals that prompt subjects to take their medications. Dosages and times can be programmed for up to 25 medications for 3 months. Adherence was assessed by drug monitoring bottle caps (eDEM) and a questionnaire measuring self-reported adherence.
Interestingly, adherence rates were not significantly different between DMAS users and patients who received only adherence counseling (80% vs. 65%), except in those patients who had problems with memory, identified by the NP tests. Post hoc analysis of 31 memory-impaired patients showed that adherence rates were significantly better in those who used the DMAS device (77%) compared with those who received only adherence counseling (57%), (p = .001), although there was no significant effect on viral load. I thought the most intriguing part of this study was the ability to identify high risk patients with "memory-impairment" who may benefit from various kinds of daily reminder systems, but I especially liked the idea of a verbal prompt.
Most physicians are aware that Roche withheld the distribution and sales of Tamiflu several weeks ago in order to prevent indiscriminate stock piling of drug badly needed for patients with Influenza A and B this coming winter.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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