Biosecurity BriefingSubscribe | About | Current Issue | RSS | Archive August 25, 2008
WHO Reports Oseltamivir Resistance in Southern HemisphereOn August 15, 2008, the World Health Organization (WHO) issued a report indicating that clinical samples from the 2008 influenza season provide evidence of a high degree of resistance to the antiviral drug oseltamivir (Tamiflu®). According to WHO, there have been “several reports from National Influenza Centres in the southern hemisphere regarding influenza A (H1N1) virus resistance to oseltamivir.”1 WHO’s report focuses on South Africa, where 139 clinical samples were isolated thus far during the 2008 influenza season. A 107-isolate subsample was tested for oseltamivir resistance, and 100% were found to be resistant to oseltamivir by genetic analysis; just one of the 107 patients with resistant strains had been receiving oseltamivir at the time of sampling. None of the 107 patients was reported to have unusual clinical features or underlying conditions. In a news report from Bloomberg, Terry Besselaar, director of South Africa's National Influenza Centre in Johannesburg commented, “The patients are from across the country, so the resistant strain is widespread.”2 The WHO report also notes that 10 of 10 A(H1N1) viruses isolated and tested in Australia, and 4 of 32 A(H1N1) viruses isolated and tested in Chile, were found to have the genetic mutation that has been associated with oseltamivir resistance. According to Bloomberg, oseltamivir resistance has been reported in 40 countries in Europe, North and South America, Africa, Asia and Australia since January. A representative from Roche, which manufactures Tamiflu®, said the company is planning “to conduct a resistance surveillance study to collect information on both the sensitive and resistant influenza infections during the 2008-2009 flu season.”2 In a summary of the findings, the European Centre for Disease Control and Prevention (ECDC) stated that, while the significance of these findings remains uncertain, the “emergence of drug resistance in the context of limited drug use is unexpected, and the extent of future circulation is difficult to predict.”3 Although there is currently no evidence that resistance is related to the use of the medicine, the ECDC will work with Roche to conduct additional surveillance and testing.2 Jennifer Nuzzo References - World Health Organization. Influenza A(H1N1) virus resistance to oseltamivir-2008 influenza season, southern hemisphere. August 20, 2008. http://www.who.int/csr/disease/influenza/H1N1webupdate20082008_kf.pdf. Accessed August 22, 2008.
- Gale J. Tamiflu-resistant flu is ‘widespread’ in South Africa (update3). August 22, 2008. Bloomberg. http://www.bloomberg.com/apps/news?pid=20601116&sid=a_Ik7zQcRNKM&refer=africa. Accessed August 22, 2008.
- European Centre for Disease Control and Prevention. Resistance to oseltamivir (Tamiflu) in some European influenza virus samples. Influenza News. August 21, 2008. http://ecdc.europa.eu/Health_topics/influenza/news/news_Influenza_080821.html#oseltamivir. Accessed August 22, 2008.
Indonesia Publishes Study on its H5N1 Cases and Factors Linked to Mortality
On August 15, 2008, The Lancet released a study in its early online publication describing the factors associated with H5N1 case fatality in Indonesia; those factors include symptoms, time to hospitalization, time to initiation of antiviral treatment, and several others. The authors, who are officials from the Indonesia Health Ministry and the World Health Organization (WHO), concluded that better diagnostic methods, faster H5N1 case recognition, and better case management would likely lead to a lower mortality rate, because these improvements would give healthcare providers the opportunity to administer antiviral medications to patients at an earlier stage of disease.1 Indonesia has developed a surveillance and patient referral system for human H5N1 infections based on WHO H5N1 case definitions. Health officers are trained to identify cases based on case definitions, conduct preliminary epidemiologic investigation of suspected cases, and take reliable patient samples for confirmatory testing at the labs. Suspected cases of H5N1 are to be sent immediately to an avian influenza referral hospital, which is at most within a day’s travel by land.1 There are currently 44 hospitals in country, and that number is being increased to 100. Since its first reported case in 2005, Indonesia has had the highest number of human cases of H5N1 in the world, with 127 cases confirmed via RT-PCR by WHO reference laboratories in Hong Kong and U.S. Centers for Disease Control and Prevention laboratories in Atlanta (from 2005 to 2007), or by two WHO-accepted national laboratories in Indonesia (after 2007). Of these 127 confirmed infections, 103 (81%) have been fatal.1 The authors note a statistically significant increase in the case fatality rate from 2005 to 2007, with fatalities increasing from 65% in 2005, to 81.8% in 2006, to 86.8% in 2007, with a slight drop to 80% in case fatality through February 2, 2008. Of the 127 patients confirmed to have H5N1, 122 were hospitalized, with a median time to hospitalization of 6 days (range 1-16 days). Of the 122 patients hospitalized, 121 (99%) had fever, 107 (88%) had cough, and 103 (84%) had dyspnea upon reaching the hospital. However, for the first 2 days of illness, symptoms were non-specific, and not all patients displayed all symptoms.1 Oseltamivir was given to 88 (69%) patients suspected of having influenza. However, some H5N1 infections were initially misdiagnosed as pneumonia or other respiratory illnesses. In those who received antiviral therapy, median time from symptom onset to initiation of treatment was 7 days (range of 0-21 days). Those patients who received treatment within 2 days of symptom onset had a significantly higher survival rate than those who received treatment 5 or more days following onset of symptoms.1 Clustering was identified as one factor linked to case fatality. Defined as “two or more confirmed cases epidemiologically linked by time and place,” 11 clusters were identified, with a total of 28 patients among them (2 to 7 individuals identified in each cluster). All of the clusters occurred among blood relatives, with a median age of 18 years. In contrast, the median age for non-clustered cases was 22 years. Mortality was lower in clustered cases, which may be due to earlier recognition and earlier initiation of antiviral treatment; oseltamivir was often started within 5 days following onset of symptoms in clustered cases vs. 8 days for non-clustered cases.1 The authors conclude that both early identification of H5N1 cases in the community and early treatment of patients in hospital are important to lowering mortality rate. They recommend increased training for community healthcare workers in early H5N1 case management; supplying healthcare workers in the field with stocks of oseltamivir; and increased surveillance of both avian and human H5N1 infections in Indonesia.1 Crystal Franco References - Kandun N, Tresnaningsih E, Purba W, et al. Factors associated with case fatality of human H5N1 virus infections in Indonesia: a case series. The Lancet. August 15, 2008. http://www.thelancet.com/journals/lancet/article/PIIS0140673608611253/fulltext?isEOP=true. Accessed August 24, 2008.
IOM Releases Summary of Workshop on Methods for Dispensing Medical Countermeasures
On August 15, 2008, the Institute of Medicine (IOM) Forum on Medical and Public Health Preparedness for Catastrophic Events released a workshop summary entitled “Dispensing Medical Countermeasures for Public Health Emergencies.”1 This workshop was held on March 3-4, 2008, and included representatives from federal, state, and local government, academia, think tanks, private sector organizations, and professional associations. The workshop objective was to “review a range of solutions to provide medical countermeasures rapidly to large numbers of people to protect them before or during a public health emergency, such as a bioterrorist attack or infectious disease outbreak.” The workshop was framed around a scenario involving the release of Bacillus anthracis, the causative agent of anthrax. According to the Principal Deputy Assistant Secretary in the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the Department of Health and Human Services (HHS), Dr. Gerald Parker, the scenario was chosen in part because an anthrax attack “brings to light the seriousness of the threat and the nation’s lack of preparedness in…dispens[ing] countermeasures within an extremely short time window to minimize morbidity and mortality from anthrax…” In addition, Dr. Parker noted that there is an “allure of anthrax…to terrorist groups because of [its] relatively low cost and ease of production and dispersal.”1 Discussion focused on different types of strategies for getting medicines out to the population following an anthrax attack within the 24-48 hours. The committee considered both “push” and “pull” mechanisms for distributing medical countermeasures. “Push” strategies are those that utilize pre-existing service systems, such as Meals on Wheels and home health care, and the U.S. Postal Service, to deliver medicines to individuals.1 Conversely, “pull” strategies for distributing medical countermeasures require people to actively pick up the countermeasures from Points of Distribution (PODs) that are open to the general public in locations such as drive-through clinics or schools. Workshop participants suggested that a layered approach to distributing medical countermeasures that relies on a mixture of both push and pull strategies could help to: 1) alleviate the strain on public health agencies during a health emergency; 2) dispense medication at a faster rate; and, 3) provide vulnerable populations, particularly those with limited mobility, greater access to medicines in an emergency.1 The IOM workshop also addressed key challenges and considerations for dispensing the contents of the SNS to a population, recognizing that “if we do not have the mechanisms to get these lifesaving medicines in the hands of Americans after such an attack or multiple attacks within a very short timeframe, we have squandered an opportunity to save lives.” One of the key recommendations resulting from the workshop was to establish partnerships between government agencies and the private sector entities to dispense medical countermeasures quickly and effectively. Ideas for improving current planning efforts included: - The public and private sector should work together to develop innovative plans for distributing medical countermeasures to the entire community within 48 hours of the decision to do so.
- States should work with local jurisdictions to streamline POD designs to increase the rate at which countermeasures are dispensed.
- Public and private partners should develop plans for alternative POD designs (such as holding closed PODs at corporate facilities for employees and their families) in order to reduce pressure on PODs that are open to the general public.
- Public health agencies should consider tapping into the resources of private sector to more effectively manage dispensing operations. For example, private sector organizations may have technology systems that could be used to track and register medicines and the people who receive them.
- Government agencies should ensure liability protection for private-sector partners that dispense countermeasures.
- Public health agencies should recruit and train a large workforce in order to sustain functionality during an emergency.
- Agencies and organizations participating in the public-private partnership should perform planning exercises that permit and encourage improvised decision making during a mass dispensing event.
- Public health agencies should collaborate with the private sector to identify the best methods for communication during an emergency, as well as, where and how medical countermeasures will be obtained.
- Public agencies should explore partnerships with private security firms to help provide security at all dispensing locations, since there may be an insufficient number of law enforcement personnel to secure POD sites.1
The workshop agenda and presentations from this workshop can be found at the Institute of Medicine website. Christine SooHoo References - Davis M, Kammersall M, Altevogt B, Rapporteurs. Dispensing medical countermeasures for public health emergencies: workshop summary. Forum on Medical and Public Health Preparedness for Catastrophic Events, Institute of Medicine. Released August 15, 2008. http://www.iom.edu/CMS/3740/42532/57467.aspx. Accessed August 18, 2008.
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