Biosecurity BriefingSubscribe | About | Current Issue | RSS | Archive September 8, 2008
Survey Finds H5N1 Knowledge Low in Afghanistan; Novavax Pandemic Vaccine Promising in Clinical TrialThe U.S. Centers for Disease Control and Prevention (CDC) has just released the results of a survey conducted to assess factors that affect the knowledge, attitudes, and practices (KAPs) regarding H5N1 in Afghanistan. Conducted in 2 H5N1 affected provinces and 3 unaffected provinces, the survey found that increased knowledge about reducing exposure to H5N1 was associated with elevated socioeconomic status and residing in an affected province, and not with owning backyard poultry.1 Although there have been no reports of human-to-human transmission of H5N1 in Afghanistan, reports of such transmission in neighboring Pakistan highlight the importance of reducing exposure and increasing reporting through a greater knowledge of the disease. Between February and April 2007, 4 of 34 Afghan provinces confirmed H5N1 in poultry; 20 of 22 outbreak sites in the 4 affected provinces involved backyard poultry. The interventions that were implemented in response included: 1) cull all poultry within a 3 kilometer radius; 2) restrict the mobility and importation of poultry; and 3) implement influenza-like illness surveillance and information, education, and communication (IEC) campaigns within the affected provinces.1 IEC campaigns were intended to prevent the spread of H5N1 in poultry, minimize human exposure to the disease, and promote increased reporting of cases. The authors found that overall knowledge of H5N1 was low in the Afghan provinces that were surveyed. Additionally, KAP scores were highest among populations exposed to IEC campaigns which did not target the provinces’ poorer populations.1 Therefore, lower socioeconomic groups have a considerably higher exposure risk due to the lack of IEC campaigns targeting these populations and the increased likeliness of poultry ownership in those populations.1 In related news, on August 26, Novavax, Inc. announced positive results from the second stage of the Phase I/IIa human clinical trial of its pandemic influenza virus-like particle (VLP) vaccine candidate. The VLP candidate is directed against the H5N1 A/Indonesia/05/2005 avian influenza strain, and “the vaccine, which does not contain an adjuvant, induced robust neutralizing antibody responses”.2 Indonesia documented 135 human cases of H5N1 since 2005, 81% of which were fatal. In the clinical trial, “the vaccine demonstrated strong neutralizing antibody titers across all three doses tested, exhibiting increasing antibody titers with the escalation of the dose.”2 Study participants received 2 injections of 15 micrograms (mcg), 45 mcg, 90 mcg or placebo. Novavax reported that 72% of individuals receiving the 15 mcg dose “had a neutralizing antibody titer of 1:20 or greater (four-fold rise from baseline)” against the H5N1 A/Indonesia strain. This was also true for 73% of individuals receiving the 45 mcg dose and 94% receiving the 90 mcg dose. Novavax also reported that “all subjects tested negative for neutralizing antibodies to the H5N1 A/Indonesia strain before vaccination and no responses were observed among individuals who received a placebo.”2 The trial is still pending complete safety follow-up; however, the Data and Safety Monitoring Board fully supports the continuation of the study up to the 90 mcg dose, as there are no reports of serious reactions. VLPs mimic the size and shape of the virus but are not capable of replication as they lack genetic material. They are able to induce a strong immune response since “they resemble actual infectious particles presenting proteins in the same conformation as on the wild-type virus”.2 Novavax’s influenza VLPs are produced in insect cell culture, which yields 7 to 10 times higher than egg-based or mammalian cell culture manufacturing. Novavax can manufacture a vaccine within 10 to 12 weeks of identifying a pandemic strain, as the technology does not require a live influenza virus, which is approximately half the time duration necessary for manufacturing egg-based vaccines.2 The data from this trial also indicates positive support for a vaccine candidate against seasonal influenza. Nidhi Bouri References - Leslie T, Billaud J, Mofleh J, Mustafa L, Yingst S. Knowledge, attitudes, and practices regarding avian influenza (H5N1), Afghanistan. Emerging Infectious Diseases. 2008;14(9). http://www.cdc.gov/EID/content/14/9/1459.htm. Accessed September 3, 2008.
- Novavax announces favorable results from phase I/IIa pandemic influenza vaccine program [news release]. Rockville, MD: Novavax, Inc.; August 26, 2008. http://www.novavax.com/download/releases/PhaseIIDataFO2.pdf. Accessed September 5, 2008.
NIAID and BARDA Award Funding to SIGA Technologies for Orthopoxvirus Antiviral
On September 3, 2008, SIGA Technologies, Inc., announced that the National Institute of Allergy and Infectious Diseases (NIAID) and the Department of Homeland Security (HHS) Office of the Biomedical Advance Research and Development Authority (BARDA), awarded the pharmaceutical company a $55 million contract to fund the development of additional formulations and smallpox-related indications for its antiviral drug ST-246TM.1 According to SIGA phase 1 clinical study published in Antimicrobial Agents and Chemotherapy in March 2008, this new funding enables the formulation and advanced development of a new ST-246TM drug product and increases the utility of the existing oral formulation of ST-246TM as a smallpox medical countermeasure.2 The study was conducted involving healthy human volunteers, and it showed that oral administration of ST-246TM prevents the spread of orthopoxvirus by inhibiting the egress of the virions. The study also showed that the antiviral is “generally tolerated with no serious adverse events.”1 In addition to its therapeutic applications, SIGA proposed that ST-246TM could have preventative applications as a prophylactic treatment for orthopoxviruses or as a supplement to vaccination. The smallpox vaccine currently stored in the Strategic National Stockpile (SNS) is associated with complications such as progressive vaccinia and eczema vaccinatum, which can be serious and even fatal.3 Combining vaccination with administration of ST-246TM could reduce complications associated with smallpox vaccination, as was demonstrated in 2007. A child with eczema vaccinatum was given ST-246TM, after the FDA approved the drug under the Emergency Use Authorization (EUA). EUA authorizes the use of drugs or products that may be effective in the prevention, diagnosis or treatment of serious or life-threatening diseases or conditions that can be caused by specified biological, chemical, radiological or nuclear agents. The child in that case recovered after receiving ST-246TM along with other medications.2 SIGA has also developed, and is awaiting FDA approval for, a manufacturing process to create substantial quantities of the antiviral drug for stockpiling.4 More studies are needed in order for ST-246TM to receive regulatory approval. Future activities also include formulation development, animal efficacy and human safety evaluations, and manufacturing.2 There are no antiviral treatments for smallpox currently approved by the FDA. ST-246TM’s efficacy is not limited to the smallpox virus. It is also been shown to be effective against other orthopoxviruses such as cowpox and monkeypox. However, variola major, the causative agent of smallpox, is the only orthopoxvirus that is considered a Category A biological threat agent by the U.S Centers for Disease Control and Prevention (CDC). Christine SooHoo References - SIGA Technologies awarded $55 million by federal government to develop broader applications for Its lead drug candidate ST-246 [news release]. New York, NY: SIGA Technologies; September 3, 2008. http://www.siga.com/?ID=81. Accessed September 4, 2008
- Jordan R, Tien D, Bolken TC, et al. Single-dose safety and pharmacokinetics of ST-246, a novel orthopoxvirus egress inhibitor. Antimicrob Agents Chemother. 2008;52(5):1721-1727. http://aac.asm.org/cgi/reprint/AAC.01303-07v1. Accessed September 4, 2008.
- Variola virus (smallpox) fact sheet. Center for Biosecurity of UPMC. Updated October 8, 2007. http://www.upmc-biosecurity.org/website/focus/agents_diseases/fact_sheets/smallpox.html. Accessed September 4, 2008.
- SIGA files application supporting emergency use approval for ST-246 [news release]. New York, NY: SIGA Technologies; March 24, 2008. http://www.siga.com/?ID=64. Accessed September 3, 2008.
Study Examines Role of Migrant Population in Re-Emergence of Tuberculosis in Beijing
The September 2008 issue of Emerging Infectious Diseases (EID) includes an article regarding tuberculosis cases in Beijing, drawing attention to the contribution of the migrant population to the total disease burden. Migrants, who comprise 1/3 of the population of Beijing and number 5 million, are increasingly seen as the cause of the re-emergence of tuberculosis in this major metropolis. Reforms in governance, beginning in 1980, permitted people to move from their native locales to other areas—chiefly farmers moving to cities in search of work. This resulted in a large migrant population within major cities. Because the highest prevalence of TB lies within the rural region, this population has the potential to spread the disease from rural areas to Beijing. Compounding this fact is that the migrant population has less access to public health services; additionally, migrants are more likely to be employed at lower income levels, which limits coverage by social medical insurance.1 Using geographic information system techniques that incorporate migrant/non-migrant population densities and tuberculosis case locations, the authors conducted a mathematical/spatial analysis of tuberculosis cases in Beijing from 2000–2006. For the purposes of the study China was divided into several geographic zones. Of the migrants studied during this time, 61.6% were male, 16.8% came from the western zones, 40.5% came from the eastern zone, 41.9% came from the middle zones, and 0.8% from Tianjin and Shanghai.1 The study included 15,078 cases of TB among residents and 7,948 cases among migrants. Results revealed that tuberculosis cases were distributed randomly among permanent residents but were clustered in migrant populations. Five districts within Beijing were discovered as “hot spots” for tuberculosis prevalence—all but one of which was associated with migrant populations. Additionally, the areas identified as “hot spots” were central (as opposed to suburban) districts, pointing to the role of high population density in the spread of TB and the ease with which TB can be spread to residents who are in closer proximity to migrants in central districts than in the suburban districts. The authors attribute their results to migrant populations having decreased access to health care and unique working conditions as well as the fact that they originate from areas of China with high TB prevalence, rendering them more likely to harbor the infection. The authors advocated for stronger TB control measures that incorporate the migrant population and raise the concern that businesspersons, travelers, and public transportation may also play a role in the transmission of TB.1 Amesh Adalja References - Jia Z-W, Jia X-W, Liu Y-X, Dye C, Chen F, Chen C-S, et al. Spatial analysis of tuberculosis cases in migrants and permanent residents, Beijing, 2000–2006. Emerg Infect Dis. 2008;14:1413-1419. http://www.cdc.gov/EID/content/14/9/1413.htm. Accessed September 3, 2008.
Australia Research Facility to Study Animal Diseases; Hendra Virus Cases Increase in Australia
On September 2, 2008, the Australian Broadcasting Corporation reported that the Australian government and the University of Queensland will be collaborating in a newly opened biosecurity research facility to study the diseases that might affect the agriculture industry.1 According to the Vice Chancellor of the University of Queensland, Paul Greenfield, the new facility represents heightened concerns about “how these [diseases] can be prevented and if they do occur how they can be minimized.”1 The new facility will give Australia the capability to research diseases such as the Hendra virus and equine influenza. In related news, Mercury, the Voice of Tasmania, reported the death of a veterinarian who was infected with a new variety of the Hendra virus while examining a dead horse. One other worker at the same location tested positive for the virus but has survived and been released from the hospital. The article noted that this represents the third human death due to the Hendra virus reported in Australia.2 Kunal Rambhia References - $33m research facility to focus on biosecurity. ABC News. September 2, 2008. http://www.abc.net.au/news/stories/2008/09/02/2353721.htm. Accessed September 4, 2008.
- Fears grow that Hendra Virus is mutating. Mercury. August 22, 2008. http://www.news.com.au/mercury/story/0,22884,24219945-421,00.html?from=public_rss. Accessed September 4, 2008.
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