Rapid National Response to Smallpox Attack in the United States
- The Issue of Smallpox
Disease History
Cause and Eradication
Smallpox, caused by variola virus, had a mortality rate of 30%, and 65-80% of survivors developed scars. Based on the idea that survivors were resistant to repeat infection, people eventually developed methods of protection, like variolation and vaccination. In the 1900s, “vaccination programs led to the interruption of smallpox transmission” in the United States and Europe, leading to the World Health Organization’s (WHO’s) global eradication campaign in 1959. This program helped reduce the number of countries with endemic smallpox, and the World Health Assembly certified the worldwide eradication of smallpox in May 1980.
History as a Bioweapon
Multiple countries have investigated using smallpox as a biological weapon. During the French and Indian War in 1763, British troops gave contaminated blankets to enemy Native American tribes. Following the global eradication of the virus, Iraq and other foreign powers have attempted to develop smallpox weapons. The most comprehensive smallpox weapons development was performed by the Soviet Union, whose bioweapons program concluded that “there was no biological weapon comparable to smallpox” because of its contagiousness, disease severity, and the lack of vaccinated enemy troops and civilians.
The Risk of Future Attacks and Outbreaks
Naïve Population
As a result of the disease’s eradication, the United States ceased giving its citizens routine smallpox vaccinations in 1972, so most Americans under the age of 53 are not protected. Smallpox could therefore quickly spread throughout the population, where each case of smallpox may result in an additional 3.5 to 6 cases. When this vulnerability is combined with the disease’s 30% mortality rate, a smallpox attack represents a serious national security threat.
Genetic Modifications of Concern
There have been three concerning cases of poxvirus gene editing in the 21st century. In 2001, Jackson et al. created a modified mousepox virus that could infect and kill vaccinated mice. Since mousepox is a model for smallpox research, this study provides evidence that variola could potentially be similarly manipulated to circumvent smallpox vaccination. Second, Rosengard et al. (2002) successfully modified a protein made by vaccinia virus (the virus used to make smallpox vaccines) to synthetically create a functional variola virus protein. Finally, in an attempt to make a safer smallpox vaccine, Noyce et al. (2018) synthetically recreated the previously extinct horsepox virus, inadvertently providing a low-skilled and inexpensive method for others to create novel variola virus particles. These studies demonstrate the potential to create new, deadlier smallpox variants using widely available genetic engineering techniques.
Modern Disease Outbreaks
Recently, two major disease outbreaks have demonstrated the US’s lack of preparedness. The nation struggled greatly during the COVID-19 pandemic, particularly in its initial onset. One report found that the US Public Health Service, composed of the Centers for Disease Control and Prevention (CDC) “and its network of state, local, and private organization partners,” failed in contact tracing, diagnostic screening for infection, promoting mask-wearing, and adequately protecting high-risk populations. Following the 2022 and 2023 global outbreak of mpox (monkeypox), a close relative of smallpox, the Government Accountability Office (GAO) criticized the Department of Health and Human Services’ (HHS’s) ineffective communication, lack of central coordination, slow deployment of medical countermeasures, and inadequate funding and workforce capacity. These failures to respond to pandemics suggest that the US would be unable to effectively react to and mitigate a smallpox outbreak.
- The Nature of a Response
Current Structure
Vaccines
The Strategic National Stockpile (SNS) houses three smallpox vaccines in the event of a smallpox outbreak: ACAM2000, Jynneos, and the APSV. The ACAM2000 vaccine features a viral strain that can replicate, so vaccine recipients can transmit the disease to close contacts. Of the three smallpox vaccines, ACAM is in the largest supply in the SNS. The APSV is not currently licensed by the US Food and Drug Administration (FDA) for use against smallpox, so it is held in the SNS as a backup for the depletion of the ACAM2000 vaccine. Jynneos, which contains a replication-defective virus, is FDA-approved for use for both smallpox and mpox. Jynneos is held in the smallest supply in the SNS and is intended for use exclusively in populations contraindicated for the other two. Both ACAM and Jynneos can be administered within 7 days of exposure to the virus, but smallpox symptoms, on average, do not appear until around 12 days post-exposure.
Government Organization
There are three mechanisms for declaring a public health emergency: by the Secretary of HHS under Section 319 of the Public Health Service Act, by a governor or chief executive under the Stafford Act, or by the president under the National Emergencies Act. Disease response activities are allocated between the Administration for Strategic Preparedness and Response (ASPR), CDC, FDA, National Institutes of Health (NIH), Indian Health Services (IHS), and Health Resources and Services Administration (HRSA). However, there is significant redundancy in these activities. For example, communication to the public about virus transmission and risk is shared by ASPR, CDC, IHS, and HRSA. Local public health departments are responsible for reporting cases to their state’s health department, which will then be shared with the CDC.
Responsibilities of HHS agencies during the 2022 mpox public health emergency. Table taken from GAO report.
Challenges
Vaccine Toxicity
The ACAM2000 vaccine is associated with numerous adverse health effects, particularly cardiovascular events. By contrast, when Jynneos was used for the mpox outbreak, cardiovascular events were incredibly rare. Additionally, ACAM has numerous contraindications, while Jynneos only has one. Jynneos also generates twice as strong of an immune response. Finally, from a financial standpoint, Jynneos is cheaper per person ($115.50 versus $139, respectively). Despite all these factors, the ACAM2000 vaccine is in greater supply in the SNS.
Disjointed Government Response
The different arms of the US government are severely uncoordinated during a public health emergency. Because responsibilities are jointly shared by several different agencies, messaging is plagued by inconsistencies. For example, the government’s response to the mpox outbreak was not cohesive until the White House stepped in to manage the response. Similarly, during the COVID-19 pandemic, each state was given the power to determine its public health response, leading to dramatically different actions. For instance, while the state of New York was one of the first states to institute a mask mandate, Missouri never instituted one. In an emergency featuring a 30% mortality rate, the lack of an overarching vision could be catastrophic.
III. The Proposal
Proposed Changes
Vaccines
The Jynneos vaccine induces a stronger immunological response and has fewer adverse effects than ACAM2000. Thus, the SNS smallpox vaccine stockpile should mostly consist of Jynneos. Since the lack of Jynneos may be attributed to a limited manufacturing capability, the US government should sign a new, substantial contract with Bavarian Nordic, the vaccine’s manufacturer. Simultaneously, because of its large number of severe side effects, ACAM2000 should be reclassified as a vaccine of last resort. There is precedent for large manufacturing contracts with Bavarian Nordic: because Jynneos was the only FDA-approved vaccine for mpox, the US Biomedical Advanced Research and Development Authority (BARDA) signed a $120 million order with the company in 2023 to make more vaccines.
Rapid National Reporting Window
In the current system, local health departments report confirmed smallpox cases to the state public health department, which will then report the case to the CDC. This system can result in delays in federal response to an outbreak. However, because most Americans are unprotected from deadly smallpox, the government must work promptly to control the spread of the disease. Thus, the CDC should create a Rapid National Reporting Window that local health departments can use to report cases of smallpox and other diseases of bioterrorism risk directly to the CDC. With this mechanism in place, the federal government will be able to immediately respond to an outbreak without first waiting for the reports to trickle through the states’ departments. The local department will still also report to the state, but there will not be an administrative delay in the federal government receiving the information.
The current system of disease case reporting is shown on the left. The addition of the Rapid National Reporting Window (right) allows for the Local Health Department to directly report to the CDC, saving crucial time.
Rapid National Response
The federal government has been too diffuse in assigning responsibilities during a public health emergency; various agencies’ responsibilities are too redundant. What follows is a proposed guide for a federal response to smallpox with as little redundancy as possible:
A confirmed case of smallpox will be directly reported from the local health department to the CDC via the proposed Rapid National Reporting Window. The CDC will communicate the information to ASPR, which will mobilize the medical countermeasures stored in the SNS. All emergency responders, healthcare workers, mortuary workers, and other personnel who will interact directly with those infected with smallpox must be protected. Therefore, the Federal Emergency Management Agency (FEMA) will be responsible for the distribution of personal protective equipment (PPE) to all essential parties. HHS will mobilize the Public Health Service to supply personnel wherever needed. State, local, tribal, and territorial (SLTT) health departments will perform surveillance with assistance from the Department of Homeland Security (DHS). The CDC will communicate information to doctors, who will be responsible for communicating with their patients and communities. However, the CDC will also communicate the same information to the public.
DHS’s involvement will allow for federal surveillance if the outbreak crosses state lines. Additionally, the federal government’s activity amid the outbreak will ensure a uniform response nationwide. Primary communication through doctors will potentially increase compliance with public health recommendations because doctors are the most trusted sources of health information, but the CDC will also communicate to the public to ensure that individuals who do not see a doctor still receive the information.
The Rapid National Response enhances efficiency and reduces redundancy in the federal government’s disease response.
Conclusion
These proposals remedy each of the identified issues. Vaccine toxicity will be far less of a problem when the SNS switches to Jynneos as the immunization of first use. ACAM2000 works better in a supporting role, used only if all the Jynneos vaccines have been exhausted. The Rapid National Reporting Window will expedite the speed with which the national government can learn about and respond to a smallpox outbreak. Finally, the Rapid National Response plan will resolve the cooperation and efficiency issues highlighted by the GAO. With the implementation of these proposed policies, the United States government will be better equipped to respond efficiently to a smallpox attack and reduce civilian suffering.
Biography of Author
Zachary H. Berliner graduated in December 2024 with an MS in Biodefense from the George Mason University Schar School of Government and Policy. I am very interested in policy related to bioweapons and health security. I also have interests in terrorism studies and counterterrorism measures. I graduated in May 2021 with an ScM from the Johns Hopkins University Bloomberg School of Public Health. My concentration was in Molecular Microbiology and Immunology.
Edited by: Aklesia Maereg, MPP &. MSI ’27 // Francisco Brady, MPP ’25 // Drew Bluethmann, MPP ’26
