Jounal Reviews

Could biodefense meds be used against H5N1 flu?

Former Soviet bioweaponeer urges FDA approval

Alibek K, Liu G. Biodefense shield and avian influenza [letter]. Emerg Infect Dis. 2006 May. On the web at www.cdc.gov/ncidod/EID/vol12no05/05-1480.htm.

The former chief scientist in the old Soviet Union’s bioweapons program emphasizes that the treatments being developed for biodefense could prove to be valuable weapons against avian influenza A virus (H5N1).

Lead author Kenneth Alibek, MD, PhD, DSc — now a distinguished professor in the department of molecular and microbiology at the National Center for Biodefense at George Mason University in Washington, DC — wrote in a letter to the editor that FDA approval of biodefense agents for H5N1 "might save many lives."

Biodefense medicine primarily concerns respiratory infections because bioweapons in their deadliest form disperse Bacillus anthracis and Yersinia pestis, the causes of anthrax and plague, and highly contagious viruses such as smallpox, Ebola, and Marburg as aerosols. The National Institutes of Health and Department of Defense have funded developing novel biodefense medications designed to stimulate innate mucosal immunity by using interferons (IFNs) and interferon inducers. "We suggest that studies begin immediately to explore the potential of IFNs to prevent infections and reduce deaths caused by avian influenza viruses in animal models and humans," Alibeck and co-author urged.

Modulating innate mucosal immunity is promising as a rapid-acting, broad-spectrum approach to combat bioterrorism. Innate immunity, the initial response to a pathogen, is potentially capable of eradicating infection. Even when the innate immune response cannot eliminate a virus, it may substantially reduce viral load, reduce pathology, facilitate clearing of the virus by the adaptive immune response, and slow the spread of infection. As biodefense medications, IFNs and IFN-inducers are under development for aerosolized delivery to the lungs.

Medications being developed to prevent infections caused by viral bioweapons and other diseases include: 1) Oral IFN-a or Alferon low-dose oral (LDO) (Hemispherx Biopharma Inc., Philadelphia); 2) inhalable IFN-g (InterMune, Brisbane, CA); 3) dsRNA [Poly (ICLC)] or Ampligen (Hemispherx Biopharma Inc.); 4) ssRNA (Aldara and Resiquimod from 3M Pharmaceuticals, St. Paul, MN); and 5) CpG7909 and CpG10101 oligonucleotides (Coley Pharmaceutical Group, Wellesley, MA). These drugs have either been approved by the Food and Drug Administration (Aldara); are in clinical trials (Alferon LDO, inhalable IFN-g, Resiquimod, CPG7909, and CpG10101); or at a preclinical stage of development (Ampligen).

"Aldara is approved for genital warts, actinic keratoses, and basal cell carcinoma," the authors note. "Other drugs are being tested for aerosolized delivery to modulate mucosal immunity of the respiratory tract. All could be expeditiously tested with inhalational or intranasal administration in H5N1 models with mice, ferrets, pigs, and monkeys."

Public health support staff may no-show in pandemic

Does not bode well for all-hazards response

Balicer RD, Omer SB, Barnett DJ, et al. Local public health workers’ perceptions toward responding to an influenza pandemic. BMC Public Health 2006; 6:99. On the web at: www.biomedcentral.com/content/pdf/1471-2458-6-99.pdf.

In findings that do not bode well for bioterrorism or all-hazards response, researchers have found that many public health care workers may abandon their posts if an influenza pandemic begins.

In a survey of Maryland public health workers that netted 308 (58%) responses, researchers found that 46% of respondents indicated they would not likely report to work during such an emergency. The U.S. pandemic influenza plan released last November lays out a critical role for local and state public health agencies during a pandemic, including: providing regular situational updates for providers; providing guidance on infection control measures for health care and nonhealth care settings; conducting or facilitating testing and investigation of pandemic influenza cases; and investigating and reporting special pandemic situations.

Moreover, the all-hazards approach currently taken in disaster planning entails an ability and willingness to respond to a broad spectrum of situations, ranging from the intentional (e.g., chemical, biological, or radiological terror) to the naturally occurring, the authors note. Current national pandemic contingency plans account for possible personnel shortages within the health care and public health settings, mainly due to the expected influenza morbidity among workers.

"Yet our data suggest that regardless of the expected morbidity among personnel during an influenza pandemic, nearly half of the local health department workers are likely not to report to duty during such an extreme public health crisis," the authors state. "In fact, most of the workers (and nearly three out of four technical/support workers) do not believe they will even be asked to report to work."

Indeed, they found that the willingness to report to duty during a pandemic varies considerably according to the individual’s job classification. The likelihood of reporting to duty was significantly greater for clinical (e.g., nurse, dentist, physician) than technical and support staff, (e.g., computer entry, clerical, receptionists). The perception of the importance of one’s role in the agency’s overall response was the single most influential factor associated with willingness to report. In general, they found that most of the workers wary about reporting for duty feel they will work under significant personal risk, in a scenario they are not adequately knowledgeable about, performing a role they are not sufficiently trained for, all the while believing this role does not have a significant impact on the agency’s overall response.

"Current contingency plans account for possible personnel shortages due to influenza morbidity, but previous studies have shown that during extreme scenarios, a varying proportion of health care workers may be unable or unwilling to report to duty," the authors noted. "This may be even truer for health departments, where unlike more "traditional" first-responder agencies (such as law enforcement, fire services, and emergency medical services), the capacity and willingness to respond 24/7 to crises is not historically ingrained in the work forces’ professional cultures and training. Even in the post-9/11 environment, recent data indicate inconsistent and sometimes slow after-hours response by health departments to urgent events involving communicable disease."

Each worker must know role

Each public health worker must have a better understanding of the scenario and importance of his or her personal role within these settings, confidence that the agency will provide adequate protective equipment for its employees, psychological support and timely information, and a belief of being well trained to cope with emergency responsibilities including the ability to communicate risk to others, they concluded.

"In view of what is currently considered to be an impending influenza pandemic, a wide gap between these desired targets and current status exists, that may lead to significant hindrance in the ability of local health departments to function adequately," they noted. "We therefore believe further efforts must be directed at ensuring that all local public health workers, but most notably nonclinical professional staff, understand in advance the importance of their role during an influenza pandemic — otherwise they will fail to show up when they are most needed."