12 January 2011
Daniel R. Lucey MD, MPH
Protecting our best weapon in treating malaria
Dr Margaret Chan (Director-General of the World Health Organization)
Statement at the launch of the Global Plan for Artemisinin Resistance Containment
Geneva, Switzerland
Ladies and gentlemen,
The report we are launching today sets out a high-level plan to protect our most potent weapon in treating malaria, the artemisinins. These medicines are the key ingredient of artemisinin-based combination therapy, or ACTs.
ACTs are the gold standard. They are the most effective treatment for falciparum malaria, the most deadly form of malaria.
Combination therapy is a deliberate strategy to delay the development of drug resistance, which inevitably happens when any antimalarial drug is widely, and especially, unwisely used.
ACTs deliver a two-punch attack on the malaria parasite. By combining drugs with different mechanisms of action and different time spans of activity, ACTs increase the likelihood that any parasites not killed by one drug will be killed by the second one.
The usefulness of these therapies is now under threat.
Evidence of resistance to artemisinins was suspected on the Cambodia-Thailand border in 2008 and confirmed in 2009. Other suspected foci have been identified in the Greater Mekong subregion, but are not yet confirmed.
This part of the world is the historical epicentre for the emergence of drug-resistant malaria parasites. History tells us what to expect.
Over the past several decades, we have lost one front-line antimalarial after another as resistance has developed, become established, and then rapidly spread internationally, rendering these drugs useless.
Today, in launching this global plan, WHO, together with Roll Back Malaria partners, is attempting to break this historical pattern. We are calling on the international community to take advantage of an unprecedented window of opportunity.
The ambition is bold: to stop the emergence of artemisinin resistance dead in its tracks, at its source, and thus prevent, or at least significantly delay, further international spread.
This opportunity is unprecedented in the history of malaria control. Why now?
Thanks to a recent surge in research, we understand malaria, and the mechanisms of drug resistance, much better. Let me thank researchers in hundreds of institutes around the world, also in endemic countries.
Their work has made it possible for WHO to compile the largest collection of studies on antimalarial drug efficacy ever reviewed and standardized for analysis.
Vigilance is at an all-time high. In fact, intensive monitoring of therapeutic efficacy has been in place, with WHO support, on the Cambodia-Thailand border since 2001. A standardized research protocol has been developed to aid similar vigilance elsewhere.
Never before have the first subtle changes in parasite sensitivity been detected so early. Never before have the tools and strategies been in place to attempt to stop the emergence and spread of drug resistance at its source.
Never before have we had such a high level of commitment to make this happen, to stay one step of ahead of at least some of the setbacks that history has taught us to expect.
We believe that the plan has every good chance of success. Above all, the international community is duty bound to seize this opportunity. Too much is at stake if we fail.
It is no exaggeration for me to say that the consequences of wide-spread resistance to artemisinins would be catastrophic.
After decades of stagnation in malaria control, stepped up efforts are finally producing impressive results, including striking drops in transmission rates and deaths. These results are invigorating, adding to the growing momentum to reduce the huge burden of malaria, especially in sub-Saharan Africa.
The spread of resistance to artemisinins and the loss of ACTs could unravel these hard-won gains very quickly and undermine the conviction that malaria can be defeated.
A large number of endemic countries have nothing left to fall back on if the ACTs begin to fail. Most older antimalarials have been rendered useless by drug resistance. While a major effort is under way to develop new classes of antimalarials, no replacement products are on the immediate horizon.
The estimated yearly number of malaria cases, though declining, is still 223 million. Leaving such a large number of people with no effective treatment would be an unthinkable tragedy.
Ladies and gentlemen,
I have two further points.
First, the containment plan is not a side-track, not a diversion of resources and efforts. Basically, what is recommended to contain resistance is what needs to be done to control malaria in every endemic country.
We need to continue to reduce transmission, through either the scaled up use of treated bednets or increased indoor residual spraying of insecticides.
Countries need to stop handing out ACTs to every child with a fever. ACTs should be treated like precious, fragile commodities, dispensed only on the basis of a confirmed diagnostic test.
This is entirely feasible. Inexpensive, quality-assured rapid diagnostic tests are now available that can be used right down to the community level.
We need to ensure that every patient with confirmed malaria gets the best, quality-assured medicines. We need to do more to prevent the sale of counterfeit or substandard medicines. We need to stop the practice of peddlers selling individual pills instead of full treatment courses.
We need to ban the marketing of therapies containing only artemisinin, and thus lacking that two-punch power of combination therapies.
These practices must be prevented as they hasten the development of drug resistance. They also undermine good overall malaria control.
My second point is this. We are launching a global plan at the start of 2011, but this does not mean that aggressive action has not already taken place. On the contrary.
Containment efforts began immediately on the Cambodia-Thailand border at the end of 2008, even before resistance was confirmed. Household coverage with treated bednets is nearly 100%.
Health facilities have been set up to diagnose and treat malaria. Services are open 24 hours a day, free of charge, and stocked with quality-assured ACTs. Intensive monitoring of therapeutic efficacy continues.
What the global plan aims to do is add another safeguard by extending vigilance and preventive measures to all endemic countries.
The emergence of artemisinin resistance has been a wake-up call. It gives us another compelling reason to step up existing control measures with the greatest sense of urgency.
The global plan spells out clearly what needs to be done. It is my sincere wish that the international community will seize this unprecedented opportunity.
Thank you.
17 Feb 2011
Daniel R. Lucey MD, MPH
Glanders (B. Mallei ) Antibiotic Post-Exposure Prophylaxis
(PEP) after a Deliberate Release: Guidelines in Europe
Glanders is a rare infection of humans caused by the gram-negative bacteria Burkholderia mallei that is included on the US CDC Category B biothreat agents. In the USA only one human case has been reported since 1950. This patient was a microbiologist at the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID) in Maryland who was working with B. mallei in the lab. (Srinivasan et al. NEJM 2001 (July 26); 345: 256-58. See also the accompanying editorial by Drs. Ali Khan and David Ashford pages 287-89 titled: “Ready or Not: Preparedness for Bioterrorism”). B. Mallei is a zoonotic infection e.g., horses and related equids; however, in the USA such infections were eliminated in 1934 (Khan and Ashford NEJM 2001; 345: 287). Thus, even one human or animal infection with glanders in the USA, or detection by an environmental sensor, would be cause for an immediate investigation and appropriately measured response.
Animal outbreaks of glanders continue to occur in other parts of the world, for example in horses (UAE 2004, Bahrain 2010) and in lions (Tehran Zoo reported January 17, 2011 in a Washington Post online/Associated Press article by Nasser Karimi, and in the Istanbul Zoo published in the German-language literature in February, 1986).
If glanders were used as an agent of bioterrorism or biowarfare then it would likely be as an inhaled form that could cause a high mortality rate due to respiratory failure. One of the immediate clinical questions would be what antibiotics could be used for post-exposure prophylaxis (PEP) to prevent symptomatic disease? The US CDC website (accessed 17 Feb 2011) on glanders lists under the subsection heading “Challenges” to “Develop post-exposure antibiotic prophylaxis strategies for bioterrorism preparedness”.
A 2008 multinational group of co-authors, including from the US CDC (Dr. Theresa Smith) and USAMRIID (Dr. David DeShazer), published guidance on “Management of Accidental laboratory Exposure to Burkholderia pseudomallei and B. mallei” (Peacock SJ et al. Emerg Infect Dis 2008 (July) ; 14 (7) online. These authors state explicitly, however, that: “The guidance does not address actions required after a bioterrorist event. (see Introduction section on page 2 of 8). Earlier guidance from USAMRIID was published by Rusnak JM et al. “Management Guidelines for Laboratory Exposure to Agents of Bioterrorism” in the Journal of Occup Environ Med (JOEM) 2004 (August); 46: 791-800 also focused on laboratory exposures (for which “doxycycline or ciprofloxacin” for 10 days was recommended for B. mallei PEP (see Table 4, page 795).
In contrast, guidelines for antibiotic post-exposure prophylaxis after a “deliberate” or “bioterrorism-related” glanders (B. mallei) event have been published in Europe in 2008 (by the UK Health Protection Agency (HPA) and in 2004 (by the European Commission (Luxembourg) Task Force on Biological and Chemical Agent Threats (BICHAT) as quoted below:
The United Kingdom (UK) Health Protection Agency (HPA): 30 October 2008 version 3.3 HPA Centre for Infections. Title: Guidelines for action in the event of a deliberate release”. See the UK HPA website (last accessed 17 Feb 2011): www.hpa.org.uk/Topics/InfectiousDiseases/InfectionAZ/GlandersDR/Guidance/
Section 2.4 (on page 9 of 20 in this pdf) provides the following verbatim guidelines under the title “Prophylaxis of persons exposed to glanders/ melioidosis”: “Although there is no evidence of a protective efficacy of post-exposure antibiotic prophylaxis in preventing human melioidosis or glanders, on the basis of animal experiments the following 7 day regimen is currently recommended for those known to have been exposed to heavy contamination:
Doxycycline 100mg twice daily
or
Co-trimoxazole 960mg oral twice daily (for children under 12 years of age sulfamethoxazole 40mg/kg and trimethoprim 8mg/kg oral daily)
Other exposed persons should be monitored and asked to self-record temperature twice daily for 21 days and to report immediately for medical attention in the event of febrile illness (temperature > 38 degrees C) or development of cough.
On the following page of these UK HPA guidelines (page 10 of 20) antibiotic prophylaxis of frontline workers is addressed as follows: Section 2.6, titled “Protection of frontline workers”, defines frontline workers as including “all emergency staff involved in management at the scene of a release, and staff involved in the care of patients.” Section 2.6.2 titled “Antibiotic Prophylaxis” provides the following verbatim guidelines:
“Frontline workers entering the exposed zone and others in the exposed area should be offered antibiotic prophylaxis (see 2.4).
Although person-to-person transmission is rare and there is little evidence of autopsy transmission (glanders only), antibiotic prophylaxis may be considered for workers involved in decontamination of exposed workers or management of patients, or mortuary staff who handle the deceased. Decisions about who should receive prophylaxis should be taken on an individual basis according to duration and degree of potential exposure, and taking into account the availability and side effects of prophylactic treatments.
In addition frontline workers involved at the scene of release and healthcare workers and mortuary staff involved in the management of cases should be advised that if they develop febrile disease they should always mention their exposure on seeking medical attention (see 2.4.2).”
(Note: This above-referenced Section 2.4.2 is titled: “Monitoring of exposed persons”. It reads as follows: “Anyone who is known to have been exposed to a deliberate release of either organisms may be at lifelong risk and should be advised always to bring this to the attention of any doctor they consult subsequently for a febrile illness.”).
In 2004 the Task Force on Biological and Chemical Agents Threats (BICHAT), Public Health Directorate, European Commission, Luxembourg published a paper in Eurosurveillance ( www.eurosurveillance.org) volume 9 issue 12; pages 1-6 titled: “BICHAT Guidelines for the Clinical Management of Glanders and Melioidosis and Bioterrorism-Related Glanders and Melioidosis”. They stated: “Post-exposure prophylaxis with trimethoprim-sulfamethoxazole (co-trimoxazole) is recommended in case of a biological attack, although this is based on experimental data: but the utility of post-exposure prophylaxis in humans is still discussed.” (No dosage or duration of co- trimoxazole was stated for PEP by the authors).
A multi-organizational committee in the USA should be convened in 2011 to reach a consensus on post-exposure prophylaxis (PEP) for glanders (Burkholderia mallei) following a deliberate release (bioterrorism or biowarfare). Such a committee should include, but not be limited to, representatives from HHS (CDC, FDA, NIH, PHECME), DHS (S& T, others), DoD (USAMRIID, USUHS, others), Infectious Disease Society of America (IDSA) State and City Health Departments (e.g., NYC DHMH, others), and other subject matter experts and involved stakeholders.
9 March 2011
Daniel R. Lucey MD, MPH
77 Powerpoint Lectures online from the International Meeting on Emerging Diseases (IMED) & Surveillance
Speaker presentations from the superb February 4-7, 2011 International Meeting on Emerging Diseases (IMED 2011) and Surveillance, International Society of Infectious Diseases (ISID), held in Vienna, Austria are now posted on a public website at: http://imed.isid.org/symposia.shtml. The Final conference program and abstract book are also available via a link at the top of this page. The chair of the conference was again Dr. Lawrence Madoff, and the IMED 2011 was larger and even better than the biannual IMED 2009 and IMED 2007.
Over 75 excellent powerpoint presentations from IMED 2011 are now available from this remarkable collection of what is, in some ways, an ‘e-state-of-the-art’ for the accelerating global field of Emerging Diseases.
A sample of the spectrum of the “One Health” topics covered during this three-day meeting included: Wildlife and Emerging Diseases, Diseases at the Wildlife-Human Frontier, Climate Change and Infectious Diseases, H1N1 Pandemic, Farm to Table: Foodborne Diseases”, Vectorborne Diseases, Surveillance and Public Health, Emerging Infectious Pathogens of Animals and Man, and others.
A sample of specific lecture presentations for which powerpoint slides are now posted online include:
Monitoring Infectious Disease Threats in Europe, Identifying New and Emerging Viruses of Bat Origin, Gideon, Emerging Diseases in Public Health Education, Animals as Detectors of Bio-events, Using Data from social Networking sites to Predict the Spread of Pandemic Influenza, Surveillance of antimicrobial Resistance and antibiotic Use in Humans and Animals, Polio—Vaccine End game Strategy, Regional disease Surveillance Networks, the ProMED Experience in East Africa, Q-fever in the Netherlands, Plague and Climate Change;
Infection prevention and control challenges experienced in the Lujo Adenovirus outbreak, Controlling Transmission of Glanders in the Veterinary Health Setting, Re-emerging mosquito-borne diseases in Europe, Cholera outbreak in Haiti, 2010, Laboratory-acquired human cowpox infection in the USL case investigation, ProMED early warnings in Africa;
Using surveillance data to estimate influenza vaccine effectiveness in Spain during seven seasons (2002-2009), Cost-effectiveness of alternative case finding strategies for prisons with high prevalence of MDR-TB, Emergence of multidrug resistant NDM-1 producing superbugs in Bangladesh, Impact of vaccination on the genetic evolution of H5N1 viruses in Egypt, SARS-coronavirus ancestors foot-prints in southeast Asia: bat colonies and the biodiversity refuge theory, Origin and genetic evolution of swine influenza A virus isolated during winter 2008-2010 in Zhejiang province, China, Zoonotic pathogens present in South African bat species, and more.
This collection of over 77 powerpoint lecture presentations, and several hundred abstracts, from this biannual International Meeting on Emerging Diseases and Surveillance (IMED) is highly recommended to clinicians, researchers, public health officials, teachers, students, and all other persons interested in this accelerating field of global Emerging Infectious Diseases.
21 April 2011
CDC Test for Anthrax Lethal Factor (LF) Quantification (e.g., in Blood and Pleural Fluid), Independent of Antibiotics, is part of the CDC Response Plan during an Anthrax Emergency
Two of the major obstacles in clinical management of patients with suspected or known inhalational anthrax appear to have moved much closer to being removed. These two obstacles are: (1) the ability to diagnose anthrax infection rapidly during the early stages of the disease, and (2) the ability to diagnose a patient who is already on antibiotics and thus will have blood cultures that fail to grow Bacillus anthracis.
Dr. Ann Boyer and colleagues from the Centers for Disease Control and Prevention (CDC) reported in the March 14 issue of the journal Molecules 2011;16:2391-2413 that their investigational mass spectrometry assay for Lethal Factor (LF), one of the components of anthrax lethal toxin, has reached the point where:
“In support of its utility and effectiveness, the LF method has been included as part of the CDC response plan during an anthrax emergency. It is also a required measurement under the investigational new drug protocol for use of the anthrax anti-toxin, anthrax immune globulin intravenous (AIGIV).”
This LF assay has been reported from studies in rabbits and non-human primates (referenced below). Published human clinical data is currently limited to one patient in 2006 (summarized below from Clin Infect Dis (April); 2007;44:968-971). Presumably more clinical data will be published in the future, involving studies on patients with other forms of anthrax (e.g.,injectional anthrax in the UK 2010 who received AIG under the CDC’s IND protocol, given the above statement by CDC that the LF measurement is required as part of their AIG IND and the publications from the UK in 2010 stating that at least some of the 52 patients with “injectional anthrax” due to heroin injection did received adjunctive AIG in addition to multiple antibiotics, surgery and other primary therapies as indicated).
Earlier in 2011 three of the CDC authors (Drs. John Barr, Ann Boyer, and Conrad Quinn) published an article summarizing their research in animals using this LF mass spectrometry assay in the Journal of Exposure Science and Environmental Epidemiology (p.573-574). They reported five encouraging features:
1) Detects infection earlier: “…as early as 12 hours after exposure to spores…Anthrax can be detected even before symptoms such as fever are present”.
2) ) Shorter time to the first result: “Quantitative lethal factor measurements and analyses are completed within 4 hours.”
3) Analyzes many more samples per day: “…automated and can analyze hundreds to thousands of samples per day.”
4) Not subject to antibiotic interference: given that the assay measures toxin, and not the bacteria that produces the toxin, then antibiotics do not inhibit measurement of the toxin. Of note, the toxin(s) (Lethal toxin and Edema toxin) persist after the B. anthracis bacteria are killed and the toxins are responsible for causing death. Thus, this LF assay might provide a rationale for initiating adjunctive therapy with anthrax anti-toxin, whether polyclonal (e.g., AIG) or monoclonal (e.g., Raxibacumab, which like AIG is in the US Strategic National Stockpile (SNS)).
5) Quantifies toxin to track course of infection and responses to treatment. Self-explanatory in that effective treatment eventually result in sustained lowering and removal of LF as a marker of anthrax toxin(s).
In my opinion, failure of LF to decrease quantitatively at all would suggest the presence of antibiotic-resistant anthrax (e.g., MDR or XDR-anthrax as defined in this Newsletter section November 23, 2010 at this website www.BePast.org).
In 2006 the one patient in the USA since 1976 to have been recognized to have naturally acquired inhalational anthrax, had one pleural fluid specimen (on Feb 19) and multiple plasma or serum samples measured using this CDC research assay for Lethal factor (LF) over the 12 day period from Feb 17-28. The patient’s blood cultures, while initially growing a gram+ rod organisms in 4/4 bottles in < 24 hours (as is consistently found for Bacillus anthracis). While these blood cultures were drawn on February 16, then were identified by PCR the next day via the Laboratory Response Network (LRN), and finally “confirmed to be B. anthracis by susceptibility to gamma-phage lysis on 22 February.”
The pleural fluid concentration of LF was higher (543 ng/ml) than any of the plasma or serum {LF} levels, emphasizing once again the crucial importance of draining the pleural fluid that is found in nearly every patient with inhalational anthrax, as proven in all 11/11 patients (including at autopsy) in 2001 in the USA. This 2006 patient was also the first person to be treated with polyclonal anthrax immune globulin (AIG) .The authors noted in their discussion that the optimal timing of administering AIG as an adjunctive therapy with combination antibiotics and aggressive supportive care might be even before the proposed intermediate-progressive stage of inhalational anthrax (e.g., the patient required mechanical ventilation, but did eventually recover unlike any prior patients in 2001 with inhalational anthrax who required mechanical ventilation).
In conclusion, development of this LF quantitative mass spectrometry test at the CDC is encouraging. A next crucial step is to make this assay rapidly available across the USA, e.g., within the Laboratory Response Network (LRN) rather than only in Atlanta at CDC given the predictable very large number of specimens that would be requested to be tested for LF in the event of another anthrax emergency, based on the experience of autumn of 2001. Hopefully, such forward positioning of the LF assay across the USA will occur prior to the autumn of 2011, and its associated commemoration of 9/11 and the anthrax letter attacks postmarked of 9/18 and October 9, 2001.
June 3, 2011
CDC Health Advisory
Distributed via Health Alert Network
CDCHAN-00322-ADV-N
Notice to Health Care Providers — Shiga Toxin-producing E. coli O104 (STEC O104:H4) Infections in U.S. Travelers Returning from Germany
CDC is monitoring a large outbreak of Shiga toxin-producing Escherichia coli O104:H4 (STEC O104:H4) infections ongoing in Germany. The responsible strain shares virulence characteristics with enteroaggregative E. coli (EAEC). As of May 31, 2011, the Robert Koch Institute (RKI) reported 470 patients with hemolytic uremic syndrome, or HUS (a severe condition associated with STEC infection that can lead to kidney failure), and nine deaths. The strain of STEC that is causing this illness, STEC O104:H4 is very rare. The illness that it causes is similar to that caused by E. coli O157:H7 or STEC O157:H7, which is also a Shiga toxin-producing E. coli.
CDC is not aware of any cases of STEC O104:H4 infection ever being previously reported in the United States. However, as of May 31, 2011, three cases of HUS in the United States have been reported in persons who recently traveled to Hamburg, Germany. CDC is working with state health departments to learn more about these suspected cases and obtain bacterial isolates for further characterization.
CDC has recommended that any person who has recently traveled to Germany and has signs or symptoms of STEC infection, or HUS, should seek medical care and let the medical provider know about the outbreak of STEC infections in Germany and the importance of being tested for STEC infection.
Symptoms of STEC infection include severe stomach cramps, diarrhea (which is often bloody) and vomiting. If there is fever, it usually is not very high. Most people get better within 5–7 days, but some patients go on to develop HUS, usually about a week after the diarrhea starts. The classic triad of findings in HUS is acute renal damage, microangiopathic hemolytic anemia (evidence of schistocytes and helmet cells on peripheral blood smear), and thrombocytopenia.
It is not recommended to give antibiotics to patients with suspected STEC infections until complete diagnostic testing can be performed and STEC infection is ruled out. Some studies have shown that administering antibiotics in patients with STEC infections might increase their risk of developing HUS. However, clinical decision making must be tailored to each individual patient. There may be indications for antibiotics in patients with severe intestinal inflammation if perforation is of concern. Of note, isolates of STEC O104:H4 from patients in Germany have demonstrated resistance to multiple antibiotics.
Guidelines to ensure as complete as possible detection and characterization of STEC infections include the following:
- All stools submitted for testing from patients with acute community-acquired diarrhea should be cultured for STEC O157:H7. These stools should be simultaneously assayed for non-O157 STEC with a test that detects the Shiga toxins or the genes encoding these toxins.
- Clinical laboratories should report and send E. coli O157:H7 isolates and Shiga toxin-positive samples to state or local public health laboratories as soon as possible for additional characterization.
- Specimens or enrichment broths in which Shiga toxin or STEC are detected, but from which O157:H7 STEC isolates are not recovered, should be forwarded as soon as possible to a state or local public health laboratory so that non-O157:H7 STEC can be isolated.
- It is often difficult to isolate STEC in stool by the time a patient presents with HUS. Immunomagnetic separation (IMS) has been shown to increase recovery of STEC from HUS patients. For any patient with HUS without a culture-confirmed STEC infection, stool can be sent to a public health laboratory that performs IMS or to the CDC (through a state public health laboratory). In addition, serum can be sent to CDC (through a state public health laboratory) for serologic testing of common STEC serogroups.
The benefits of adhering to the recommended testing strategy include early diagnosis, improved patient outcome, and detection of all STEC serotypes.
All patients with Shiga toxin-positive diarrheal illness or HUS should be reported to health departments, regardless of a travel history to Germany.
For more information:
http://www.rki.de/EN/Home/homepage__node.html
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August 9, 2011
News Release
Health officials investigate case of inhalational anthrax from suspected natural environmental exposure
Officials say case does not represent increased risk to general public
The Minnesota Department of Health (MDH) is working with the Centers for Disease Control and Prevention (CDC) to investigate an apparent case of inhalational anthrax in an individual who officials believe acquired the infection from the natural environment. The individual was hospitalized in Minnesota after traveling through western states, including North Dakota, Montana, Wyoming, and South Dakota. Laboratory analysis in Minnesota confirmed the diagnosis of anthrax.
“All evidence points to this case of anthrax being caused by exposure to naturally occurring anthrax in the environment,” said Minnesota State Epidemiologist Ruth Lynfield. The individual had exposure to soil and animal remains. Cases of anthrax in hooved animals occur yearly in parts of the country including the Midwest and West as far south as Texas, and up to the Canadian border.
Because anthrax can be used as a bioterrorism agent, the Federal Bureau of Investigation (FBI) investigated this matter jointly with MDH, but no evidence suggesting it was a criminal or terrorist act was obtained. As such, the FBI is no longer actively investigating the incident.
Health officials stressed that the case does not represent an increased risk of anthrax to the public. “Anthrax is not spread from person to person, and it is extremely rare for humans to become sickened with anthrax, especially through inhalation,” Lynfieldsaid. In rare cases, individuals can become sickened by anthrax if they handle infected animal carcasses or ingest contaminated soil or meat from infected animals. People can also become infected by handling contaminated wool or hides or other products from infected animals. In years past, anthrax was known as “woolsorter’s disease”.
Because these cases are so rare, health officials are not discouraging people from traveling to areas where anthrax can be found naturally in the environment.
The individual is being treated at a Minnesota hospital.
More information on anthrax, symptoms and treatment, can be found on the MDH website at http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anthrax.html.
August 26, 2011
News Update
Contact information
Health officials update information on anthrax case
The Minnesota Department of Health in collaboration with the Centers for Disease Control and Prevention (CDC) has been investigating a case of inhalation anthrax. The individual, a man in his 60s, had traveled through several states in July and early August, where anthrax is known to be in the soil and to have caused infections in animals, including North Dakota, South Dakota,Montana and Wyoming. He was hospitalized in early August with pneumonia, was determined to have inhalation anthrax and is now recovering. The Bacillus anthracis strain isolated from the patient was found by genetic testing to be similar to other strains isolated in North America. The individual had a prior chronic lung condition, which may have made him more susceptible to infection with anthrax, and had multiple exposures to soil and animal products. No other human cases of anthrax have been reported in 2011.
October 18, 2011
Testimony of the Honorable Tara O’Toole, M.D., M.P.H. before the U.S. Senate Committee on Homeland Security and Governmental Affairs
Dirksen Senate Office Building
Introduction
Good morning Chairman Lieberman, Ranking Member Collins, and distinguished Members of the Committee. It is an honor to appear before you today to discuss the state of U.S biodefense ten years after letters containing Bacillus anthracis or “anthrax” killed five people and sickened seventeen others and to report on the biodefense portfolio within the Department of Homeland Security’s (DHS) Science and Technology Directorate (S&T). In the decade since the Amerithrax incident there have been significant gains in the country’s ability to detect, respond to and recover from a deliberate bioattack or a natural epidemic of infectious disease.
Designing and implementing a viable biodefense is a complex undertaking. U.S. efforts to date have engaged multiple Federal agencies, national laboratories, state and local governments, first responders, the medical and public health communities, the private sector and individual American households. International biodefense collaborations involving U.S. allies are underway. President Obama and Secretary Napolitano regard biosecurity as a top national priority. The President’s recent address to the U.N. General Assembly urged all nations “to come together to prevent, detect and fight every kind of biological danger – whether it is a pandemic like H1N1, a terrorist threat, or a treatable disease.”
Overview of Biological Defense Programs at the Science and Technology Directorate
Since its creation in 2002, the Department of Homeland Security’s Science and Technology Directorate (DHS S&T) has made many contributions to US biodefense in the form of knowledge products (analyses, standards, assays), new technologies and technical tools and through participation in various Interagency processes. S&T’s efforts have been especially focused on:
- Biothreat studies – deepening our understanding of the specific biothreat agents of greatest concern to better focus national preparedness and response activities,
- Detection and Identification of bioagents -developing science-based strategies, practices and technologies required for the timely detection of covert biological attacks, including the development and fielding of the original Biowatch technology, and the precise identification of biothreat agents,
- Environmental remediation and area recovery – determining feasible and effective means of identifying and remediating the environmental contamination left in the wake of bioattacks,
- Essential Biodefense Laboratory Infrastructure – building and operating national laboratories essential to biodefense, such as the National Biodefense Analysis and Countermeasures Center (NBACC), the Plum Island Animal Disease Center (PIADC), and the National BioAgro Defense Facility (NBAF),
- Biodefense for Agriculture – conducting, in collaboration with the US Department of Agriculture (USDA), front line research in biodefense of US agricultural assets, including the development of diagnostics, medicines and vaccines relevant to foreign animal diseases
- Bioforensics – establishing a sound technical and operational basis for conducting forensic investigations of bioattacks and biocrimes.
DHS S&T staff have been highly active participants and leaders in numerous, ongoing Federal Interagency efforts to advance USbiodefense. I co-chair the National Science and Technology Committee on National and Homeland Security, along with Mr. Zack Lemnios of the Department of Defense (DoD) and Phil Coyle, Associate Director of the White House Office of Science and Technology Policy. Our scientists serve on 32 Committees and Working Groups across the interagency. These working groups and committees examine the full range of biodefense issues from dual-use research, bioterrorism threat intelligence, and first responder detection CONOPs, to diagnostics and the development of medical countermeasures (MCM). These efforts involve all of the executive branch partners including Department of Health and Human Services (HHS), USDA, DoD, Department of Justice, and Environmental Protection Agency (EPA).
While there are still important challenges ahead of us, these extensive efforts have resulted in a government and citizenry considerably more prepared to respond to and recover from a biological attack than we were a decade ago. DHS S&T has been an important part of this progress. Building upon the work started in the national labs and other federal agencies, S&T has crafted a portfolio that addresses the full continuum of the threat. My testimony will provide an overview of the bioterror threat and DHS S&T’s biodefense work.
The Bioterror Threat is Real and Will Grow as Bioscience Advances
Ten years after anthrax was mailed to members of the U.S. Congress and to media organizations, dozens of policy, intelligence, and technical reports have affirmed the viability of terrorist groups using biological weapons to cause death, suffering, and socio-economic disruption on a calamitous scale. In 2008, the Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism stated that it, “…is more likely than not that a weapon of mass destruction will be used in a terrorist attack somewhere in the world by the end of 2013.” S&T has worked diligently to increase understanding of the full spectrum of potential threats and their consequences.
More than a decade ago, the Defense Science Board affirmed that, “there are no technical barriers to a large-scale bioattack.”2 We are living in the midst of a biotechnology revolution where the knowledge and tools needed to acquire and disseminate a biological weapon are increasingly accessible. It is possible today to manipulate pathogens’ characteristics (e.g. virulence, antibiotic resistance), and even to synthesize viruses from scratch. These procedures will inexorably become simpler and more available across the globe as technology continues to mature. Thankfully, the combination of technical expertise required and the restrictions limiting the acquisition of the materials necessary for production still make this a challenging task.
Even small-scale attacks could be highly lethal and disruptive, and as has been noted, there is a real possibility of a campaign of bioattacks on multiple targets (the “reload” phenomenon) – because these weapons are self-replicating organisms. Moreover, it is not necessary for a nation-state to maintain a large stockpile of bioweapons to pose a significant asymmetric threat as the development of a significant offensive bioattack capability could occur within weeks or months.
DHS S&T Biothreat Studies
Understanding the biological threat and the relative risk posed by biological agents is a fundamental need for any biodefense capability. Homeland Security Presidential Directive 10: Biodefense for the 21st Century, DHS S&T has the responsibility to conduct the Biological Terrorism Risk Assessment (BTRA) every two years. The BTRA has been developed in partnership with experts in the law enforcement and intelligence communities, along with input from the scientific, medical, and public health communities, and serves as a starting point for biodefense investment priorities.
The BTRA is a comprehensive, strategic-level assessment designed to 1) aid in identifying and prioritizing credible, high impact threats, 2) aid in identifying and prioritizing vulnerabilities and knowledge gaps, and 3) provide a systematic, science-based, common framework for “what if” analyses. At its core, the BTRA is a model. It does not predict the future, but provides a way to think logically, using common assumptions, about more and less likely possible futures. The BTRA approach encompasses a wide variety of possible attack scenarios to ensure that the assessment outcomes are comprehensive. Consider the scope of the 2010 study which examined:
- 4 types of terrorists (international, state-sponsored, domestic, lone wolf) exploiting
- 43 different bioagents (38 human, five livestock pathogens) that may be obtained from
- 2 locations (foreign and domestic) by
- 5 routes of acquisition (among them theft and environmental isolation) with
- 6 methods of production and weaponization to attack
- 20 different targets (including a subway, stadium, transportation or outdoor events) using
- 8 modes of dissemination (e.g. food, aerosol) causing exposure by
- 2 routes (inhalation or ingestion) resulting in
- 3 public health consequences (illnesses, fatalities, and economic consequences).
The end result is millions of enumerated scenarios of what is possible in bioterrorism. To date, S&T has conducted BTRAs in 2006, 2008 and 2010. Additionally, S&T conducts companion analyses such as the Chemical Terrorism Risk Assessments (conducted in 2008 and 2010), the Radiological and Nuclear Terrorism Risk Assessment (conducted in 2010) and the Integrated Terrorism Risk Assessments (conducted in 2008 and 2010). These risk assessments are used by other Federal departments and agencies to guide their CBRN response planning.
The strength of the BTRA is due in large part to the work conducted by the National Biological Threat Characterization Center (NBTCC). This unique, national-level S&T asset was created by DHS in 2004 as part of the NBACC to address gaps in our knowledge related to high priority biological threat agents and to help support decisions regarding biodefense resource prioritization. The NBTCC performs scientific experiments to address the critical knowledge gaps related to acquisition, production, and dissemination in order to ensure an effective knowledge base for critical decision making in biological defense.
The most significant utilization of the BTRA is its role in providing risk input in shaping the multi-million dollar MCM investment decisions of the HHS. The Project BioShield Act of 2004 outlines the multi-step process utilized by DHS and HHS to ensure that the nation’s MCM research, development, and acquisition activities are grounded in a risk-based process. In summary, as identified in the BTRA, the bio-agents which present the greatest risk to the U.S. population are further analyzed in a Material Threat Assessment (MTA) process led by DHS’s Biodefense Knowledge Center, located at Lawrence Livermore National Laboratory. During the MTA process, DHS evaluates the intelligence and threat information for top priority agents and develops and models a “highly plausible” consequence scenario includes the number of potentially exposed individuals. The MTAs are provided to HHS, which then conducts further analysis to determine public health impacts. DHS and HHS work collaboratively to review all of these data and determine if an agent poses a significant national security threat. Based on these deliberations, the Secretary of Homeland Security issues a Material Threat Determination (MTD).
To date, DHS has issued 11 MTDs for biological agents, two MTDs for classes of chemical agents, one MTD for radiological materials, and one MTD for nuclear detonation effects. The MTD is a statutory requirement for procurements using BioShield funds; however the issuance of an MTD does not guarantee that the government will pursue countermeasures against that agent. If an MCM is sought, DHS has a statutory responsibility alongside HHS in recommending to the Office of Management and Budget to release the BioShield Special Reserve Funds.
Biological Surveillance, Detection, and Diagnostic Capabilities
Early indication of a biological attack is very challenging due to the dual-use nature of the required knowledge and materials and the small size of operational footprint necessary to produce the agents making detection difficult. In the absence of pre-attack interdiction, it is crucial that the U.S. has the means to detect and mitigate an attack either through large-scale technology programs such as BioWatch or through enhancing the capabilities of First Responders and Public Health professionals by, for example, the creation of better methods for detecting bioagents in the field or conducting reliable lab analyses. Other S&T investments also work to create sensors which could automatically initiate protective actions (e.g. altering a building’s airflow patterns) as well as develop rapid diagnostic capabilities as both a means of detection and a critical element to help mitigate an attack by guiding our response.
Standard Field Protocol for Rapid Resolution of Suspicious White Powders: Since 2001, responses to incidents involving suspicious “white powders” have impacted the First Responder community; these events are often costly and disruptive. S&T has invested in tools to both reduce the cost and impacts of these responses and to standardize the responses to ensure that any real events are optimally handled.
S&T has led an interagency effort with the Center for Disease Control and Prevention (CDC), Federal Bureau of Investigation (FBI), EPA and National Institute of Standards and Technology to develop multiple standards on bulk and swab sample collection of suspected biothreat powders and operational guidelines for initial response to a suspected biothreat agent to ensure that the procedures and sampling strategies used are effective and support confirmation and prosecution if a real incident were to occur. These standards were published by the American Society for Testing and Materials, an international standards organization in 2010. These standards are increasingly being adopted by First Responders and are already in use by multiple states and the FBI.
Rapid Portable BioDetector for First Responders: S&T is developing technology intended to evaluate suspicious powders in the field in a matter of minutes. Although laboratory confirmation is the only way to reliably determine the presence of a biological organism, this technology will help emergency responders assess a threat.
Detect to Protect (D2P): Current biodetection systems are designed to “detect to treat”. Studies done by S&T of bioattacks and chemical attacks on subways and by DOD at the Pentagon show that bio-aerosols can spread throughout a subway system or building very quickly. These investigations highlight the need for very rapid, tight connections between initial detection of a release and response actions. Such “detect to protect” systems are challenging to build, because they must balance the need for a fast detection against the fact that fast detection sensors are prone to false alarms.
To address these difficulties, S&T is pursuing a multi-tiered bio-aerosol DP2 program for sensing a bioattack within metro systems, airports, buildings, and stadia. Low cost, rapid “trigger” sensors when tripped immediately initiate “behind the scenes” protective actions to slow spread of an agent, such as changing air flows within a space while turning on a confirmation sensor. The confirmation sensors are high confidence detection technologies provide the high confidence analysis necessary to support high-impact actions such as building evacuations or warnings to shelter in place or alerting of public health officials. Such a multi-tiered detection approach not only helps reduce the spread of the agent and the extent of human exposure in near-real time, but could also reduce system costs by decreasing the required number of expensive confirmer sensors. S&T is currently conducting operational tests and evaluations on the D2P system within the Boston Metro (Massachusetts Bay Transportation Authority – MBTA).
Assay development and standards: A key element of any successful detection or diagnostic tool is the assay which provides the ability to discern the unique molecular signatures of an agent. DHS S&T has a highly robust bioassay program that is focused on the development of improved assays as well as standards and test methodologies to foster confidence in deployed detection systems. Some of the aspects of assay development currently ongoing include:
- Efforts that focus on the creation of highly specific assays with the ability to differentiate microbes at the sub species. This is important because different sub species will have very different impacts on human health. This level of resolution is essential information for public health officials.
- The recent development of a rapid Ricin Detection Assay with extremely high specificity and sensitivity. This assay is currently undergoing its final validation study and is anticipated to be deployed through the Center for Disease Control and Prevention’s (CDC) Laboratory Response Network (LRN) before the end of the calendar year.
DHS S&T has led the interagency in the development of standards that guide the appropriate levels of sensitivity and specificity needed for assays deployed in various environments. There are generally two levels of standards for assays, one for use by First Responders when making decisions to evacuate buildings or close off streets, and another used by the CDC to declare medical emergencies and issue medications. Working with the Association of Analytical Communities and their Stakeholder Panel on Agent Detection Assays S&T developed the consensus standards for Public Safety Actionable Assays (PSAA) to support the testing and validation of commercial technologies that might be used by the First Responders in the field. A much higher standard of performance is needed for those assays designed to be used by the CDC LRN when making high-impact public health decisions such as the distribution of antibiotics. At the request of the White House in Fiscal Year 2008, S&T has been working with our Interagency partners including the CDC, DoD, State and Local public health authorities to develop the Federal Standards for Assay Performance and Equivalency (FSAPE) which specifically aims to ensure a common standard for sensitivity and specificity for assays that will be used to make public health actionable decisions. This process is nearing completion and has already received the buy-in from multiple stakeholders in the public health community.
Any bio-detection architecture needs to be a coordinated effort leveraging multiple federal laboratories for sample analysis and public health decisions. S&T led in the establishment of the Integrated Consortium of Laboratory Networks (ICLN) to serve this purpose The ICLN coordinates a network of laboratories that, in the case of an act of bioterrorism, will be accountable for provision of timely, credible, and interpretable data in support of surveillance, early detection, and effective consequence management. By coordinating Federal labs, the ICLN can take a risk-based approach to events and minimize capability gaps of individual labs.
Advanced Biodiagnostics: Currently, there are no approved, point-of-care clinical diagnostic tests that physicians could use to determine if an individual is infected with a bioterror threat agent. The traditional diagnostic approach involves blood culture analysis which requires one or more days to deliver results. In situations where outcomes depend on rapid treatment after exposure, or in mass casualty situations where scarce resources must be deployed intelligently, the ability to rapidly identify infected victims is a strategic necessity. DHS S&T, in partnership with the DoD Defense Threat Reduction Agency, the National Labs, and the CDC, are pursuing an effort to develop a broad-spectrum diagnostic with the potential to identify exposure to biological agents prior to the onset of symptoms.
Rapid Test for Antibiotic Susceptibility: DHS S&T, in collaboration with the CDC, has developed a rapid assay to determine antibiotic susceptibility for B. anthracis and Y. pestis. These rapid assays reduce the timeline for answers by 50% compared to the gold standard conventional susceptibility assay. Given that some of the biothreat agents possess very short incubation periods for disease onset and are coupled with high mortality rates after symptomology, the need for rapid antimicrobial susceptibility assays is critical.
Response and Recovery from Bioattacks
Much of our national biodefense investment focuses on detection of and medical treatment for a biological attack. However, it is equally essential to develop capabilities, protocols and technologies that support rapid attribution to identify the source of the attack as well as help an impacted area quickly and appropriately respond to and recover from an attack
Bioattack response and recovery operations are complex and much work remains to be done in this arena. The Environmental Protection Agency (EPA) has the lead in the area of environmental restoration but it is widely acknowledged that the EPA budget is too small to support a robust program. DHS S&T, as well as DoD, have made strategic investments in this area and several of the efforts have yielded valuable insights that I would like to bring to your attention.
Responding to an Attack: S&T’s biodefense investments include the development of guidance and technologies to diminish uncertainty and enhance data-driven decisions in the hours and days after an epidemic is first detected. Immediately following a bioattack there will be a critical need for “situational awareness” – information leaders will need to guide the response – but reliable data will be hard to obtain quickly with current systems, technologies, biosurveillance capacities and communication flows. During the initial days following a covert attack, there is likely to be significant uncertainty regarding whether the observed epidemic is natural or deliberate, the scale of the attack, where the attack occurred; who was exposed; whether the bioagent is susceptible to specific antibiotics, whether and where the environment is contaminated, whether and where there might be additional attacks, etc.
Viable Particle Capture Device: This program is developing a low-cost deployable device that continuously samples the air and collects and stores any airborne particles or pathogens in a manner that keeps them viable for laboratory analysis. Because of the low-cost nature of the device it can be widely deployed throughout a city as an augmentation of the BioWatch network and after an attack has been detected the additional sample points would greatly increase the knowledge of where an agent had been dispersed. Even more importantly, the device ensures that any agent collected during an attack is viable allowing laboratories to identify it and test it for virulence and anti-biotic resistance.
Multi-Application Multiplex Technology Platform (MAMTP): The testing systems currently in use at the Laboratory Response Network labs that process the BioWatch samples were designed around the public health mission and are not optimized to support a Biodefense surveillance system in terms of the number of agents that can be tested and throughput. The MAMTP is a technology platform that will be able to perform up to 100 tests or detect 100 targets simultaneously within a single sample. The platform will use a standardized cartridge system to reduce costs and aid in surge capacity which will be needed to handle the thousands of samples that will be collected after an attack in an effort to identify where the agent has spread.
Anthrax Re-aerosolization: A significant question with regard to anthrax attacks is whether the anthrax bacteria, which are unusual as they are protected by an extremely hardy spore coat that makes it resistant to environmental degradation, could become “re-aerosolized” and continue to pose a health threat once it is deposited on surfaces following the initial attack. The answer has significant implications for remediation strategies, but existing data is limited and contradictory. DHS S&T, in partnership with DoD, EPA and the national labs, is conducting studies to understand this problem within urban areas. These studies will address gaps in our understanding and will inform key policy decisions for evacuation vs. shelter-in-place, distribution of medical countermeasures, clean-up, and re-occupancy.
Recovery from an Attack: It is essential that the Nation have the capability to rapidly restore buildings, public infrastructure and critical utilities to full-function after an attack. This need is especially pertinent in the context of anthrax, because of the long-lived nature of this microbe, but understanding the extent, duration and consequences of post-attack contamination needs to be further explored.
Interagency Biological Restoration Demonstration (IBRD): This interagency effort included partnerships with state and local governments in the Seattle Urban Area and was co-funded with the DoD’s Defense Threat Reduction Agency. The IBRD program developed a Seattle Region Plan for determining approaches for response and restoration activities, which served as the foundation for the development of the “Interim Consequence Management Guidance for a Wide-Area Biological Attack” document that can be used by other cities.
Mass Transit System Biological and Chemical Dispersion Studies: S&T studied releases of simulated biological and chemical agents in the Boston subway and DC metro systems to determine how material would move, disperse, deposit and could be mitigated through fast acting detection systems and changes to the airflow control systems. This effort is being continued through a partnership with the Washington Area Metropolitan Transit Authority to conduct simulated attacks on the Metro system to develop response protocols and above-ground countermeasure requirements.
Bioforensics: In 2001, there existed numerous challenges associated with microbial forensics investigative capabilities. Among them were no biocontainment lab, staff or equipment singly dedicated to microbial forensic analysis and limited evidence handling processes peer-reviewed analytical methodologies, or quality guidelines. Today, S&T owns and operates a national asset for biological forensics and attribution, the National Bioforensics Analysis Center (NBFAC), which is part of NBACC, was established by HSPD10 as “the lead Federal facility to conduct and facilitate the technical forensic analysis and interpretation of materials recovered following a biological attack in support of the appropriate lead Federal agency.” S&T owns and operates this national asset for biological forensics and attribution.
The NBFAC provides 24/7 support for biocrime and bioterror investigations for the Federal Bureau of Investigation (FBI), DHS Customs and Border Protections , the U.S. Secret Service and other government agencies with dedicated staff, equipment and biocontainment laboratories designed specifically for bioforensic analysis. The NBFAC has developed sensitive and specific assay capabilities for more than 60 bacterial, viral and toxin agents and has processed over 8,000 samples and completed 137 cases in support of Federal Law Enforcement agencies. The NBFAC also maintains a Bioforensic Reference Repository collection of geographically and temporally diverse biological agents to support comparative forensic analyses. The NBFAC trains FBI examiners to safely handle biologically contaminated evidence and supports traditional forensic exams. As a result of NBFAC, the U.S. can now do in days to weeks what previously required months.
Construction of the National Bio- and Agro- defense Facility
S&T was charged by Congress to design and build the National Bio- and Agro-defense Facility (NBAF), a laboratory with the capacity to perform research and development work on large animals at the highest (BSL-4) laboratory biosafety containment levels. After an extensive three year competition and evaluation, Manhattan, Kansas was selected as the site for NBAF. Since 2009, Congress has appropriated $154 million for NBAF design, site preparation and construction. The state of Kansas has pledged to contribute $110 million towards construction costs and has donated land for the site. The total remaining cost of NBAF construction was estimated as of 2011 to be $874 million. Construction of this facility, which is an essential part of the US biodefense infrastructure, is dependent upon continued support from Congress.
For more than 50 years, the Plum Island Animal Disease Center (PIADC) has served as the primary US laboratory facility for conducting vital livestock disease research. Despite its many successes, the age of PIADC facilities, its limited capacity restricts research and is impeding the development of needed countermeasures. PIADC has no capacity to do research at the Biosafety Level 4 (BSL-4), the highest bio-safety level, which is essential to combating the most dangerous animal disease threats. Currently, the U.S. must rely on partnerships with large animal BSL-4 labs in Australia and Canada. In the event of a bioattack on agriculture, or an attack employing a zoonotic disease, the U.S. would be unable to do the research needed for response. PIADC has no surge capacity for response to wide-scale events and its island location off the coast of New York limits operations in adverse weather conditions. Failure to build the NBAF will not only place the security of US agriculture in jeopardy, but would seriously impair U.S. scientific eminence in this important field.
S&T’s R&D efforts are subject to ongoing review
Biodefense is just one of the many areas addressed by S&T’s diverse portfolio. To ensure that individual R&D projects are meeting the goals established by our partners in the operating components and the broader homeland security enterprise (HSE), S&T has committed to an annual review of our portfolio of basic and applied R&D and all proposed “new start” projects. The review process consists of written materials, an oral presentation by the project manager, and careful analysis of the project’s likely impact and feasibility (or “riskiness”) as judged against specific metrics determined by S&T with input from the operating components. These metrics are designed to address elements essential to programmatic success in the context of the DHS’s QHSR missions, namely:
- Impact: Is our portfolio making a significant impact on our customer’s mission?
- Transition: Are we transitioning relevant products to the field?
- Technical Positioning: Is our investment positioning the organization for the future?
- Customer Alignment: Are our projects aligned with well-understood customer requirements?
- Customer Involvement: Do we have the appropriate level of customer interaction?
- Innovation: Are we sufficiently innovative in the way we approach our challenges?
A review panel of S&T leaders, the DHS Component representatives, and outside experts evaluates and rates each project. By measuring all of our projects against this framework, we will provide a transparent and “shareable” view of all R&D within S&T; enable more strategic, longer-term budget decisions; ensure efficient delivery to the component or end user; and nurture effective communication throughout the process. This particular review model has been used by both Federal and private R&D organizations, including the prize-winning Army Engineering, Research and Development Laboratory. Review is key to ensure that S&T remains focused on the highest priority challenges in biodefense and ensuring that our work is complementary, not duplicative, of other agencies.
Challenges Remain for Biodefense
The design and implementation of a robust, cohesive, and cost-effective biodefense system will be the work of a generation. Despite the significant gains made over the past decade, much work remains to be done to deal with today’s – and tomorrow’s – challenges. As President Obama has noted, true biodefense against both deliberate and natural epidemics of infectious disease must be an international endeavor.
In the coming years, the DHS S&T Directorate intends to focus its resources on developing capacities to detect bioattacks in near-real time in order to enhance protective response actions. There will also likely be calls to improve detection of a wider range of potential threat agents, including genetically altered, synthetic or unanticipated agents, and possibly to enable detection of food and surface contamination. Faster, more detailed and reliable characterization of bioevents to improve situational awareness and inform response will be necessary. We must continue to develop an agile approach that accommodates possible epidemics of emerging disease or attacks using unforeseen bioagents or agents not addressed by stockpiled countermeasures. Inexpensive, real-time, point-of-care diagnostics will be essential to enabling rapid identification and treatment of those at risk from epidemic disease and to containing the spread of contagious disease. Strategies for coping with and stopping bioterror campaigns must be developed. Mechanisms of international cooperation in dealing with infectious disease outbreaks and collaborative approaches to financing and refining needed biodefense technologies and countermeasures must evolve.
It is critical to understand that bioscience is in a state of revolution. Advances in our understanding of living systems and our technological ability to manipulate these systems are proceeding globally at a breathtaking pace. The biothreat landscape of the next ten years will not resemble today’s. The technologies, tools and capabilities being developed need to be viewed not just through the lens of today’s threat agent list, but from the perspective of capabilities available to our adversaries in the future.
Thank you for the opportunity to appear before you today. I am happy to answer any questions you might have.
30 December 2011
WHO concerned that new H5N1 influenza research could undermine the 2011 Pandemic Influenza Preparedness Framework
Statement
The World Health Organization (WHO) takes note that studies undertaken by several institutions on whether changes in the H5N1 influenza virus can make it more transmissible between humans have raised concern about the possible risks and misuses associated with this research. WHO is also deeply concerned about the potential negative consequences. However, WHO also notes that studies conducted under appropriate conditions must continue to take place so that critical scientific knowledge needed to reduce the risks posed by the H5N1 virus continues to increase.
H5N1 influenza viruses are a significant health risk to people for several reasons. Although this type of influenza does not infect humans often, when it does, approximately 60% of those infected die. In addition, because these viruses can cause such severe illness in people, scientists are especially concerned that this type of influenza could one day mutate so it spreads easily between people and causes a very serious influenza pandemic.
Research which can improve the understanding of these viruses and can reduce the public health risk is a scientific and public health imperative. In order to enable those public health gains, countries where these viruses occur should share their influenza viruses for public health purposes while countries and organizations receiving these viruses should share benefits resulting from the virus sharing. Both types of sharing are on equal footing and equally important parts of the collective global actions needed to protect public health.
While it is clear that conducting research to gain such knowledge must continue, it is also clear that certain research, and especially that which can generate more dangerous forms of the virus than those which already exist, has risks. Therefore such research should be done only after all important public health risks and benefits have been identified and reviewed, and it is certain that the necessary protections to minimize the potential for negative consequences are in place.
In May 2011, the new Pandemic Influenza Preparedness (PIP) Framework came into effect. This Framework was adopted by all WHO Member States as a guide to the sharing of influenza viruses with pandemic potential and the resulting benefits. One specific requirement of this Framework, which pertains to influenza viruses of pandemic potential, and is in keeping with best scientific practice, is for laboratories receiving them through WHO’s Global Influenza Surveillance and Response System (GISRS) to collaborate with, and appropriately acknowledge, scientists in countries where the virus originated when initiating research.
WHO recognizes that the scientists who led the work of the new studies received their virus samples from the WHO Global Influenza Surveillance Network (GISN), which preceded GISRS, and before negotiations on the new PIP Framework began.However, now that the Framework has been adopted by all WHO Member States, WHO considers it critically important that scientists who undertake research with influenza viruses with pandemic potential samples fully abide by the new requirements.
Since the PIP Framework represents a major step forward and was agreed upon only after several years of difficult negotiations, WHO stresses that this H5N1 research must not undermine this major public health achievement. WHO will work with MemberStates and other key parties to ensure scientists understand the new requirements that have been agreed to with the Framework.
Race against time to develop new antibiotics
The second part of a series of three news features on antimicrobial resistance looks at how the antibiotics pipeline is drying up while resistance to existing drugs is increasing. Theresa Braine reports.
Bulletin of the World Health Organization 2011;89:88–89. doi:10.2471/BLT.11.030211
Within a few days of scraping his leg in a scooter accident in 2009, nine-year-old Brock Wade was in hospital fighting for his life with a methicillin-resistant Staphylococcus aureus (MRSA) infection. Once the infection – caused by one of the bacteria most often resistant to antibiotics – had been diagnosed, doctors put him on five different antibiotics. “After a month in the hospital, and against all odds, Brock recovered and was well enough to come home,” says his mother Rhonda Bailey-Wade on the web site of the Infectious Diseases Society of America (IDSA).
Scenarios such as this IDSA case study are increasingly being played out all over the world. But not all the thousands of patients that contract drug-resistant bacterial infections every year are as lucky as Brock. And the problem looks set to get worse. While infectious agents are becoming more and more resistant to the medicines that are currently in use, not enough drugs are being developed to combat them.
Courtesy of Infectious Diseases Society of America
Young Brock Wade spent a month in hospital fighting an antibiotic-resistant infection.
“MRSA continues to be a major cause of community-acquired antibiotic resistant infections,” says Dr Brad Spellberg, one of the authors of the 2004 IDSA report Bad bugs, no drugs. “However, because companies in the late 1980s and early 1990s recognized the threat of MRSA, starting in 2000 we did get new MRSA drugs. Right now, we have reasonable antibiotics to treat MRSA. As resistance catches up with them, in the future we will have problems again.”
There are many reasons. One is scientific. “The low-hanging fruit has been picked,” says Spellberg. “But the concept that we’ve exhausted the pantry is ridiculous. Now we have to dig deeper, think harder and more cleverly.”
Another reason is commercial. Antibiotics, in particular, have a poor return on investment because they are taken for a short period of time and cure their target disease. In contrast, drugs that treat chronic illness, such as high blood pressure, are taken daily for the rest of a patient’s life. “Companies have figured out that they make a lot more money selling the latter drugs than they do selling antibiotics,” Spellberg says, highlighting the lack of incentive for companies to develop antibiotics.
That’s why many companies have stopped developing antibiotics altogether. Only five major pharmaceutical companies – albeit five of the biggest – GlaxoSmithKline, Novartis, AstraZeneca, Merck and Pfizer, still had active antibacterial discovery programmes in 2008, according to an article published in the journal Clinical Infectious Diseases in January 2009.
Adding to the grim picture, a comprehensive study of antibiotic development, covering innovative, small firms, as well as pharmagiants, found in 2008 that only 15 antibiotics of 167 under development had a new mechanism of action with the potential to meet the challenge of multidrug resistance. Most of those were in the early phases of development, according to the study entitled Thebacterial challenge: time to react.
But there is hope. “Given that the antibiotics we have available today were discovered as growth byproducts of bacteria that we can culture, and that we’ve cultured less than 1% of the bacteria on our planet, there are many potential solutions out there,” Spellberg says.
WHO/Chadin Tephaval
Checking vials of biological samples at Thailand’s National Institute of Health in Bangkok.
A variety of biological solutions have yet to be fully explored, such as phage therapy and the potential use of the lytic enzymes found in mucus and saliva to kill pathogens (as described by researchers in an article published in October 2010 in the Institute of Physics’ journal Physical Biology).
Another example is that of researchers at GlaxoSmithKline who recently described a novel class of antibacterial agents that target type IIA topoisomerases. The article was published in Nature in August 2010. “This investigational compound class has activity against a broad spectrum of Gram-positive and Gram-negative bacteria,” says Dr Mick Gwyn, the study’s lead author and a researcher in antibacterial drug discovery at GlaxoSmithKline.
Antimicrobial resistance is the inevitable consequence of prescribing antibiotics. “Whatever infections we treat, the bacteria that are part of our normal flora are always exposed to these antibiotics,” says Dr Hajo Grundmann, chair of infectious diseases and epidemiology at the University of Groningen and head of the Department of Bacteriology at the National Institute of Public Health in the Netherlands. “Simply by surviving the onslaught of antibiotics, they are developing more clever ways to overcome the most sophisticated and advanced antibiotics.”
There are no global data on the number of cases, including fatal ones, of resistant bacterial infections. According to the 2008 study, every year at least 25 000 patients in the European Union alone die from an infection caused by multidrug-resistant bacteria and estimated additional health-care costs and productivity losses are at least 1.5 billion Euros.
Some of the most resistant infections are caused by Gram-negative Acinetobacter, and by certain strains of Klebsiella and Pseudomonas species, according to Spellberg. These bacteria cause a variety of illnesses ranging from hospital-acquired pneumonia, bloodstream infections, urinary tract infections from catheters, abdominal infections and even meningitis in people who have had head and spine procedures, for example, epidurals during labour.
“Anywhere in the body can be hit by these bugs. And the issue is that without effective antibiotics the death rate is much higher,” says Spellberg.
WHO/Chadin Tephaval
A laboratory technician at Thailand’s National Institute of Health in Bangkok.
The outbreak of resistant strains of Escherichia coli (E. coli) – a common cause of food poisoning – carrying a gene called NDM1 (New Delhi metallo-β-lactamase) in India in 2010, which spread to other countries, is a case in point. Until recently such completely resistant bacteria have only been found in hospitals, Spellberg says, but “now we’re starting to see virtually or totally pan-resistant bacteria spilling into the community”.
The solution may lie not only in scientific discovery but also in the economic incentives for developing drugs. “I think that Congress understands that this is now a market failure and that economic incentives are needed to correct the market failure,” he says.
Public–private partnerships could provide one solution, according to a May 2010 commentary in the British Medical Journal, such as the GlaxoSmithKline research partnerships with the Wellcome Trust and with the United States Defence Threat Reduction Agency.
Referring to “the twin challenges of conserving the effectiveness of existing antibacterial drugs and developing new ones”, authors of the British Medical Journal article Anthony So, Melissa Furlong and Andreas Heddini of Swedish-based nongovernmental organization, ReAct, write that “delinking research and development costs from drug pricing and the return that drug companies receive on investment could correct misaligned economic incentives”.
This delinking of research costs and drug pricing is something that industry may be prepared to accept, according to Richard Bergström, director-general of LIF, the trade association for the research-based pharmaceutical industry in Sweden.
“Incentives that separate the financial return from the use of a product are the only way to change this behaviour,” said Bergströmat a conference held at Uppsala University in September 2010. “Intelligent pull incentives, such as advance commitments and prizes, provide financial rewards to the developer that are not based on the volume of use of the novel antibiotic. With the right set-up, pharma companies will have no incentive to drive use. Maybe they will not do any promotion at all. Use would be agreed with public policy-makers, purchasers and national health systems.”
Bergström called for a “global compact” similar to the one used for the United Nations programme for good governance and sustainable development enshrined in Millennium Development Goal 7. This agreement “could focus on the agreed and gradual introduction – and responsible marketing and use of – new agents”.
“A global compact would require that not only industry but also governments, physicians and pharmacists join forces to preserve the new medicines that our children and grandchildren need,” said Bergström. “No single tool will solve the problem. What is really needed is a collection of incentives that address the multiple obstacles to success.”
This year the World Health Organization is devoting World Health Day on 7 April to raising awareness around the issue of antimicrobial resistance. More information is available at: http://www.who.int/world-health-day