Threat of Biological Warfare Must Now be Recognized

By William T. Elliott, MD, FACP

The threat of biological warfare is suddenly on everyone’s mind. Two of the biggest threats are smallpox and anthrax. Smallpox, which was officially declared eradicated from the planet in 1979, may represent the biggest threat. Samples of the virus were retained by the Soviet Union and the United States during the Cold War, but with the break up of the Soviet Union there is fear that some of the virus may have fallen into the hands of terrorists. British biotechnology company Acambis Plc has been developing a smallpox vaccine and announced in mid-September that it will begin clinical trials on the drug next year. The earliest that a smallpox vaccine could be in general usage is 2004, although the company is hoping that process may be accelerated. The US company BioPort is the sole manufacturer of anthrax vaccine. The company has just completed a major renovation of its manufacturing plant, which needs to be inspected and approved. Even with an accelerated manufacturing process, it is unlikely that the anthrax vaccine will be available to anyone except US military personnel in the foreseeable future. Meanwhile, the Centers for Disease Control (CDC) are focusing on treatment of anthrax. Last year the FDA approved ciprofloxacin as a treatment for anthrax and there are already reports that medical facilities and individuals are stocking up on the antibiotic.

Hepatitis C

Peginterferon plus ribavirin may become the new standard for treating chronic hepatitis C infections. Interferon alfa-2b plus ribavirin has been standard initial therapy for chronic hepatitis C, however, a new study suggests that a regimen of peginterferon and ribavirin produces higher sustained virologic response rates. Peginterferon is produced by attaching polyethylene glycol to interferon alfa-2b. The resulting compound has a longer serum half-life and may be given as a weekly injection, instead of daily, as is usually required for interferon alfa-2b. The study involved 1530 patients with chronic hepatitis C who were randomized to receive a standard interferon plus ribavirin or peginterferon plus ribavirin. Peginterferon was dosed at 1.5 µg/kg/wk, 1.5 µg/kg/wk for 4 weeks followed by 0.5 mg/kg/wk for the duration of study. At the end of 24 weeks, the high-dose peg interferon group had a significantly higher sustained virologic response rate than either the low-dose interferon group or the interfeon alpha-2b plus ribavirin group (54% vs 47%). The benefits were most apparent in patients with HCV genotype 1. Based on this study, Manns and colleagues suggest that peginterferon plus ribavirin will become the new standard for treatment of hepatitis C (Manns MP, et al. Lancet. 2001;358:958-965).

Acute hepatitis C is an infrequently diagnosed condition that often progresses to chronic hepatitis C. A new study emphasizes the importance of recognizing acute hepatitis C since treatment with interferon is highly effective in preventing progression to the chronic form of the infection. German investigators identified 44 patients with acute hepatitis C between 1998 and 2001. Patients included men and women who had been infected via needlestick, IV drug use, sexual contact, medical procedures, or undetermined causes. All patients were treated with interferon alfa-2b subcutaneously daily for 4 weeks then 3 times a week for another 20 weeks. At the end of therapy, 42 of 43 patients who completed therapy had undetectable levels of HCV RNA and normal liver function tests. The New England Journal of Medicine will publish the full text of this study in November, however because of the importance of the findings, the abstract was posted on their web site on Oct. 1. The same group that reported these findings are also working on similar studies with peginterferon.

Influenza Vaccine

This year’s influenza vaccine seems well matched to worldwide flu strains according to the US Centers for Disease Control. Two influenza A viruses and 1 B virus have been found worldwide, but there have been few isolates in North America. Still, the CDC feels we will be well prepared once the vaccine is in general circulation. Production problems have slowed this year’s vaccine, but more than half the nearly 80 million doses should be available at the end of this month, with the rest available in November and December.

Inhaled Glucocorticids

Premenopausal women on inhaled glucocorticoids may be at risk for osteoporosis according to a new study. Israel and associates from Harvard looked at 109 premenopausal women on inhaled triamcinolone for asthma. A dose-related decline in bone density at the hip, but not the spine, was found over the 3 years of the study. Even excluding women who required short courses of oral steroids, the number of puffs per year was associated with the decline in bone density. Bone density was assessed using dual photon absorbtiometry (Israel E, et al. N Engl J Med. 2001;345:941-947).

Statins

At a time when there is much public concern over side effects of statins, Astra-Zeneca is hoping to launch the most potent statin yet next year. Rosuvastatin (Crestor) is touted as being more effective at lowering LDL than atorvastatin (Lipitor), simvastatin (Zocor), or pravastatin (Pravachol). All this with a favorable side effect profile according to the company. Meanwhile, patients remain cautious about statin use following the well-publicized withdrawal of cerivistatin (Baycol) from the market. Cerivistatin, which was nearly 10 times more likely than other statins to cause rhabdomyolysis, was withdrawn in August. News reports frequently mentioned that all statins can cause muscle inflammation, but failed to point out the low overall risk.

ED

Several drugs for the treatment of erectile dysfunction are in various stages of the approval at the FDA. Icos’ tadalafil (Cialis) has been accepted for review by the agency. Tadalafil is an oral phosphodiesterases inhibitor similar to sildenafil (Viagra). NexMed is in phase III trails with a topical formulation of alprostadil with the company’s transdermal delivery technology. TAP’s apomorphine (Uprima) is currently in limbo. The drug was being reviewed by the FDA when the application for approval was withdrawn. The drug is available in Europe.