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Updates

By Carol A. Kemper, MD, FACP

April 1, 2013
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By Carol A. Kemper, MD, FACP, Section Editor: Updates, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, is Associate Editor for Infectious Disease Alert.

The economics of HIV treatment

Walensky RP, et al. Economic savings versus health losses: The cost-effectiveness of generic antiretroviral therapy in the United States. Ann Intern Med 2013;158: 84-92.

A tripla ® is a branded, combination once-daily tablet recommended as first-line anti-retroviral therapy (ART) for HIV in the United States (containing tenofovir-emtricitabine-efavirenz). However, as of January 2012, some similar drugs are now available as generics in the U.S. Therefore, a combination of generic lamivudine, generic efavirenz, and branded Tenofovir, which is a similar, if not quite as effective, combination as Atripla, could be used in the treatment of HIV infection, and would significantly reduce the cost of HIV treatment in the U.S.

Walensky and colleagues compared the relative Quality-Adjusted Life-Year (QALY) and cost-effectiveness of the branded ART combination pill vs the 3-drug generic combination therapy. Estimates of the difference in effectiveness of the 3-drug regimen compared with Atripla were factored into the assessment. The authors do allow however, that the compliance of patients on a 3-pill a day vs one-pill a day regimen may also be reduced, also reducing the potential effectiveness of the combination regimen. Branded Atripla per person per year costs approximately $19,870 wholesale. Assuming standard wholesale discounting for all drugs, the annual per person treatment for Atripla vs the generic combination regimen is $15,300 vs $9200 per person per year, respectively.

The discounted per person QALY, from age 43 years, was 4.05 for no ART, 12.08 for the 3-drug generic combination regimen, and 12.45 yrs for the branded ART. The estimated per person cost, factoring in costs of routine clinical care and laboratory monitoring, was $131,200 for no ART, $300,300 for generic combination ART, and $342,800 for branded ART.

When factoring in estimates of efficacy and failure, the incremental cost effectiveness ratio (ICER) per QALY was significantly greater for branded Atripla compared with generic drug combination (an ICER of $114,800/QALY). The deeper the discount for generic medications, the greater the difference in ICER between the two regimens. Even modest price reductions in the generic medications had a sizeable impact on the relative ICER. The authors estimate that $920 million dollars would be saved annually if all eligible U.S. patients started or were switched to the 3-drug generic combination treatment.

Honeybees and tetracycline resistance

Tian B, et al. Long-term exposure to antibiotics has caused accumulation of resistance determinants in the gut microbiota of honeybees. mBIO 3(6):3000377-12.http://dx.doi.org/10/1128/mbio. (and accompanying editorial)_.

In the United States, tetracyclines (e.g., oxytetracycline) are commonly used in the domestic honeybee industry to prevent bacterial super-infections. These authors examined the microflora of the honeybee gut for evidence of tetracycline resistance, and surprisingly found that the relatively tiny gut of the honeybee has a diverse set of tetracycline resistance genes (8 different genes!). Most of the honeybee gut flora is comprised of gram negative organisms, but resistance genes were found in both gram positives and in gram negatives. Most of the bacteria harboring the resistance genes were considered commensals and not pathogens. PCN/Ampicillin resistance was also detected in some bees, although neither agent was used in the tested hives. This suggests that extensive use of a single antibiotic can place sufficient selective pressure on organisms to promote mechanisms of resistance leading to multi-drug resistance, as has been demonstrated in other species (e.g., chickens and humans). By comparison, European bees, where tetracyclines are not commonly used by beekeepers, do not harbor tetracycline resistance genes. Since the fly has been demonstrated to pass resistant strains of E. coli among farm animals, the honeybee, which forages up to 2-3 miles away from the hive, could be a ready disseminator for antibiotic resistance in the greater ecosystem.

Catching the flu

1. Catching the Flu: NIOSH research on Airborne Influenza transmission (Http://blogs.cdc.gov/niosh-science-blog/2013/01/catchingtheflu);

2. Blachere FM, et al. Measurement of airborne influenza virus in a hospital emergency department. Clin Infect Dis 2009; 48: 438-40.

Our Emergency Department had a recent spate of Influenza illness in employees (despite prior annual influenza vaccination) – two of whom came to work despite fever and cough. Employee Health promptly instituted screening procedures for all ED employees prior to the start of their shift (temperature and symptom assessment). In total 12 employees went out ill. It’s good to remember that the typical incubation period for the flu is 1-4 days (average, 2 days), and adults may shed Influenza virus one day prior to symptom onset and up to 5-6 days after symptom onset. Children can shed virus for 10 or more days after symptom onset, and immunocompromised patients with Influenza can shed virus for up to weeks or months.

Influenza is primarily transmitted by large-particle respiratory droplet transmission, e.g., when infected people cough, sneeze or talk. Large droplets settle to the ground almost immediately (> 50 micrometers in diam.), but intermediate droplets (10-50 micrometers in diam.) may take several minutes. Smaller droplets (<10 micrometers in diam.) and what they call evaporated droplet nuclei, which are larger particles that have lost water, may take hours to settle to the ground. Virus may also be spread through contact (and fomites) as well as airborne transmission. The relative significance of these routes of transmission to health care workers is not known.

In order to test how well different personal protective equipment works to protect health care workers from large droplets and small aerosols, NIOSH has designed a custom-built coughing machine that can cough an aerosol much like a patient – and a breathing machine that simulates a person taking a breath.1 The multi-hospital NIOSH investigation will also measure the amount of virus on gloves, face masks, respirators and equipment and furniture. Researchers are also attempting to develop better methods for measuring viable virus in samples.

Blachere and colleagues tested aerosolized particles for Influenza virus in an emergency room setting using a two-stage cyclone aerosol sampler (which samples particles of varying size). The equipement was set up in various sites within the ED on 6 afternoons and collected 74 aerosol samples. Seven physicians wore personal aerosol samplers for 3-4 hours each. Real-time PCR was used to assess the presence of Influenza A matrix gene (M1). Eight of the aerosol samples were positive for Influenza A, all of which were found in the waiting room or triage. More than half of the particles detected (53%) were of a size that could readily be inhaled into the deep respiratory tract. Three of 7 of physician samples (43%) were also positive for influenza virus.

Influenza virus is indeed freely floating about the ED during the influenza season; presumably at least some of this is viable virus. I’ll remember this as I wander thru the ED on my way home at night !

Rapid detection of Plague

DePalma A. “Reliving nightmare of Plague, 10 years on”, The New York Times, Science Times section. 2013;D5-D6.

Each year, the WHO reports 1000-2000 world-wide cases of plague, most of which occurs in Africa (mostly Madagascar). The disease is, however, present at low levels in the United States, mostly in New Mexico, Arizona, Texas, California (where it subsists in low levels in rodents and the prairie dog population in the Southwest, and rodents and Jack Rabbits in California), with rare cases in Nevada, Oregon, Idaho and Wyoming. Larger carnivores and domestic cats and dogs can acquire infection from infected fleas and rodents, especially during the warmer summer months, and spread it to humans. An average of 7 human cases occur annually in the U.S (range, 1-17 cases per year); no human cases were reported in California in 2011 and 2012, but two cases in New Mexico and in Oregon in 2012 occurred as the result of contact with infected domestic cats.

Despite the availability of cheap and effective antibiotic therapy, the disease remains frequently fatal (11%-38% of the time), often within days, in large part because of the delay in recognition and laboratory confirmation of infection. Even in the United States, it can take days for the lab to get back a positive culture or a serology; and the problem is even worse in clinics or rural areas in Africa.

A simple “dipstick” test-kit has been developed to rapidly detect the presence of Yersinia pestis–specific F1-capsular antigen. The test is based on a simple immunochromatographic dipstick (much like a pregnancy test), provides rapid results (much like a pregnancy test), and is 100% sensitive and specific for both bubonic and pneumonic forms of the disease. In field tests, it worked better than the standard ELIZA test or cultures, and allows physicians or clinicians in more remote or rural locations to quickly confirm infection and start appropriate antibiotics.

Although the NY Times indicates the tests costs less than $1 per dipstick, I found the BADD Plague Detection kit for $245 for a box of 10. It has a shelf life of 2 years, does not require refrigeration, and functions in hot weather up to 120 degrees F.