Scientific Challenges
How do authorities keep track of a disease that moves quickly from person to person, city to city, country to country? How do they plan their responses to a virus that is notoriously unpredictable? This section explains the major scientific challenges to preparing for an influenza pandemic.
Uncertainty
Scientists can now identify the frequent small mutations in the evolving seasonal flu strains and map the
bigger genetic reshuffling that can create new pandemic subtypes. That information may advance vaccines, vaccine production, and treatment, but so far it has not helped researchers predict which flu viruses will become pandemic, or when.
When a new pandemic virus emerges, public health officials and other decision makers must take action quickly, well before information on the severity, transmissibility, and natural history of the virus is available.
Even when information becomes available, the numbers may not be right. Policy makers need to make decisions that account for the possibility that things are better or worse than they appear.
In the early phases, authorities must weigh the urgency of early action and possible harm of a greater outbreak against the risks and costs of interventions.
Most pandemic planning has been directed toward an extremely severe pandemic, as witnessed in the 1918-19 pandemic and as dreaded if H5N1 begins to spread easily from person to person. Each pandemic holds new lessons for preparing for the next one.
Tip: Harvard-Epidemiologist Mark Lipsitch explains
how journalists can deal with such uncertainties in their reporting.
Surveillance: How dangerous is the virus?
Surveillance refers to the recording of cases, such as how many illnesses and deaths occur, what changes over time, the severity, and risks to specific groups. The results may change as the virus spreads and changes.
The severity of the virus is characterized by how many people get sick and how many of them die. However, this is not always easy to keep track of. For example, no large jurisdiction in the world has been able to maintain an accurate count of total H1N1 cases once the epidemic exceeded hundreds of cases. Why? Because the number of new infections grew much faster than the health systems could confirm and count cases. In June, the World Health Organization advised countries to stop trying to count every case.
Scientists and health officials have been scrambling to develop different ways to track 2009 H1N1 infections and to analyze the limited numbers they have more effectively. The death rate, for example, is an important trigger for mitigation strategies, which begin with non-pharmaceutical inventions to buy time until a vaccine can be produced in sufficient quantities.
Since May, preliminary scientific findings have been made available online at
PLoS Currents: Influenza, an expertly moderated, but not peer reviewed, collection of new scientific data, analyses and ideas.
For example, a
working paper posted on Sept. 25, 2009 reports that 2009 H1N1 infected many more children but hit 18- 64-year-olds much harder. The estimate was based on data in Milwaukee and New York from April to July. Such findings suggest high priorities groups for vaccination and early treatment.
Surveillance: How do we know?
Flu reporting in the traditional public health infrastructure involves a partnership among the WHO, CDC, state, and local health departments, public health and private clinical laboratories, vital statistics offices, health care providers, clinics, and emergency departments. A major drawback is the time that lapses after the data is collected but before it can be analyzed. (Reasons for delays range from lack of technology to lack of compliance.).
Newer Internet-based electronic surveillance systems add informal channels, ranging from press reports to blogs to chat rooms to analyses of Web searches. These may speed recognition of an outbreak, prevent governments from suppressing outbreak information, and aid public health responses to outbreaks and emerging diseases. Drawbacks include information overload, false reports, disproportionate media interest, lack of verification and follow up, lack of context, and public fear.
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The HealthMap
Global Disease Alert Map creates a visual mash-up of many of these electronic feeds. This spring, for example, the system collected early media reports from the Mexican press, beginning with an April story about a "mysterious" influenza-like illness that infected up to 60% of the 3,000 inhabitants and killed two since early March. A new iPhone application allows users to submit outbreak reports directly, as well as view the HealthMap data in their geographic area.
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Surveillance: What do we need to know?
The
President’s Council of Advisors on Science and Technology (
PCAST) developed six surveillance questions to provide the necessary data to federal decision makers crafting responses to the pandemic:
| 1. |
Roughly how many people are becoming infected, getting sick, seeking medical care, being hospitalized, requiring intensive care, and dying from H1N1? |
| 2. |
How are the numbers changing over time? |
| 3. |
Who is at greatest risk of becoming infected and most susceptible to severe outcomes? |
| 4. |
How is the virus changing? |
| 5. |
Are the medical and public health systems able to respond adequately? |
| 6. |
How well do medical and public health responses work? |
The report outlines an ambitious surveillance system that upgrades the current national surveillance systems in time for Fall 2009 by integrating and expanding existing systems.
Surveillance: Who needs to know and why?
| • |
Federal decision-makers: to inform policies and recommendations about the priority groups for vaccination and treatment, to calibrate the intensity of social mitigation interventions, and to provide guidance to clinicians about appropriate treatment and prevention. |
| • |
State and local decision-makers: to understand the situation in their communities, which may differ from the national picture. |
| • |
Clinicians: to target scarce treatment to the appropriate patients, improve clinical treatment, and implement surge capacity plans in the event of increased demands on the health care system. |
| • |
The general public: to understand the size and severity of the outbreak and be motivated to comply with social mitigation measures, according to PCAST and other government preparedness planners. Historically, compliance improves when the epidemic is perceived to be severe.3 |
Vaccines
Influenza vaccines can be given to children older than six months. The biggest scientific challenge with respect to pandemic preparedness is that developing a pandemic vaccine currently takes about six months, which is rarely enough time for the vaccine to be administered to a population before a second pandemic wave arrives. And even if the vaccine were ready, current global production capacity can cover far fewer people than are at risk worldwide. (Also see
global challenges.)
Adjuvants can greatly increase the potency of vaccines and extend the number of people who can be vaccinated with a given supply. However, as of October 2009, none were approved for use with influenza vaccines in the United States. Adjuvants have, however, been approved and are being used with influenza vaccines in Europe.
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The PCAST report recommends faster assessment and licensing of adjuvants that are compatible with influenza vaccines.
Vaccine production
Vaccines have been produced in eggs since the 1940s. One of the reasons it takes so long to make a pandemic vaccine is that roughly 900 million chicken eggs are needed to make vaccine for 300 million people. Scientists have been working on new approaches to make vaccines, such as:
| 1. |
Cell-based vaccines. These are furthest along. Viruses are grown in cultured cells rather than eggs. This method potentially increases production levels and may shorten the time period between virus identification and vaccine availability by a month or two (from six to nine months). Several companies are using this approach to produce candidate 2009-H1N1 vaccines and are licensed in Europe but not in the United States. |
| 2. |
Recombinant vaccines still require more studies of safety and immunogenicity. Several methods to produce influenza virus vaccine proteins by molecular biology techniques are under development and evaluation, including some by industry and by the Defense Advanced Research Projects Administration (DARPA). This approach has potential to shorten the time between vaccine strain identification and final vaccine production to as little as a few months, as well as provide a large increase in vaccine production volume. |
| 3. |
Other basic research strives for new kinds of influenza vaccines with longer-lasting immunity against a wider range of viruses. Approaches include understanding the immunity-inducing virus proteins, three-dimensional protein structure, the mechanisms of immune recognition, and the highly variable sites on the virus. |
Antivirals
Vaccines and social distancing will remain the primary preventions.
Antiviral drugs used to treat influenza may also be used for prevention, for example to provide additional protection to emergency responders and other critical personnel. This is especially true if a vaccine is not yet available or may not yet have prompted the full immune protection.
The limited supply of antivirals, however, raises sticky questions. For example, if a group is targeted to receive priority prophylaxis or treatment, will their family members also be given first priority?
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Researchers have raised concerns about the potential rise of drug resistant pandemic strains and the need to monitor resistance rates in the virus. Drug resistance in the virus may reduce, but not completely offset, the benefits of an antiviral drug used to control a pandemic.
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Sources
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Brownstein, John S., Freifeld, Clark C., Madoff, Lawrence C., “Influenza A (H1N1) virus, 2009—online monitoring,” New England Journal of Medicine 360 (May 21, 2009): 2156. ↑
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Brownstein, John S., Freifeld, Clark C., Madoff, Lawrence C., “Digital disease detection—harnessing the Web for public health surveillance,”, New England Journal of Medicine 360 (May 21, 2009): 2153-2155. ↑
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President’s Council of Advisors on Science and Technology, Report to the President on U.S. Preparations for 2009-H1N1 Influenza, Aug. 7, 2009. ↑
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Centers for Disease Control and Prevention, Influenza A (H1N1) 2009 Monovalent Vaccine Safety Monitoring: CDC Planning Recommendations for State, Local, Tribal, and Territorial Health Officials, August 21, 2009. ↑
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World Health Organization, WHO guidelines on the use of vaccines and antivirals during influenza pandemics, 2004.
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S.M. Moghadas, C.S. Bowman, G. Rost, et. al., “Population-Wide Emergence of Antiviral Resistance during Pandemic Influenza,” PLoS ONE 3 (March 19, 2008): 1-8. ↑