Public Health Response Activities

Medical providers will contact their state health department if they suspect a patient of theirs might have smallpox. CDC will also consult with state or local public health departments and the patient's medical team to confirm or rule out the disease, especially for the first patient(s) who present with a rash illness suggestive of smallpox.

Take steps now to ensure your department and local healthcare providers will communicate and collaborate easily in an emergency.

• Document contact information for the different roles needed during an outbreak. Identify individuals, if possible. Distribute the list and include email addresses and phone numbers. Make sure this list includes the best way to contact key individuals during non-business hours. Schedule regular reviews to make sure this list stays up-to-date.
• Inventory the number, location, and typical availability of Airborne-Infection Isolation Rooms (AIIR) in the community. Also determine the surge capacity of the healthcare facilities with AIIRs.
• Work with healthcare facilities to determine procedures to ensure probable or confirmed smallpox patients could be isolated in an AIIR or transferred to a facility with an available AIIR as quickly as possible.

Federal and state public health authorities will use the information gathered through enhanced surveillance and case reporting to monitor the success of control efforts. Enhanced surveillance plans should include how to:

• Ensure rapid identification and reporting of additional cases after an initial case is confirmed (within jurisdiction or elsewhere).
• Conduct epidemiological analysis to estimate the population at risk, identify unexpected epidemiological features of the outbreak, and evaluate the characteristics and extent of the outbreak to develop the most effective containment and communication strategies.
• Increase laboratory testing capabilities to quickly diagnose cases of smallpox and differentiate suspected cases from other illnesses and adverse reactions to the vaccine.
• Monitor and report serious adverse events to vaccination.

Case definition

The clinical case definition of smallpox is an illness with acute onset of fever ≥101°F (38.3°C) followed by a rash characterized by firm, deep-seated vesicles or pustules in the same stage of development in the same area of the body without other apparent cause. See Evaluating Patients for Smallpox: Acute, Generalized Vesicular or Pustular Rash Illness Protocol. If consultation among medical providers, state and local public health departments, and CDC determines a patient is at high risk of having smallpox, Laboratory Response Network (LRN) laboratories will conduct diagnostic testing for variola virus. CDC will conduct concurrent, confirmatory testing. Variola virus is a select agent and is subject to 42 Code of Federal Regulations Part 73.

Once an outbreak has been confirmed, classify cases as confirmed, probable, and suspect using the following definitions:

• Confirmed case: A case of smallpox that is laboratory confirmed, or a case that meets the clinical case definition that is epidemiologically linked to a laboratory confirmed case.
• Probable case: A case that meets the clinical case definition, or a case that does not meet the clinical case definition but is clinically consistent with smallpox and has an epidemiological link to a confirmed case of smallpox. Examples of clinical presentations of smallpox that would not meet the ordinary type (pre-event) clinical case definition are: a) hemorrhagic type, b) flat type, and c) variola sine eruptione.
• Suspect case: A case with a febrile rash illness, with fever preceding development of rash by 1 to 4 days.

Case reporting

Local public health departments with jurisdiction over an area with confirmed smallpox cases will need to report information about cases to their state public health departments. Public health authorities will use this information to make informed decisions about the best course of action to stop the outbreak.

The extent of the outbreak and the resources available will affect the level of investigation and reporting of smallpox cases. At minimum, public health departments should submit aggregate reports of cases and deaths by age group.

Prepare for effective surveillance by:

• Educating medical and public health workers on the case definitions and case classifications for smallpox and chickenpox (varicella), the disease most often confused for smallpox.
• Establishing capability to do rapid diagnostic tests for varicella zoster virus infections (both varicella and disseminated herpes zoster).
• Developing information management systems to monitor calls and reports received.
• Building capability for enhanced rash illness surveillance.
• Designating case reporting mechanisms.
• Designating a centralized location for reporting suspect smallpox cases with 24/7 capability.
• Identifying and testing after hours and emergency notification systems and ensuring that on-call staff has appropriate access to communication resources, such as cell phones and laptops.
• Developing data management and reporting procedures for cases of disease and for serious adverse events from vaccination.

After the diagnosis of a patient with smallpox in a community, especially if it is the first case confirmed in the United States, the state epidemiologist or designee should coordinate an epidemiological investigation in collaboration with federal authorities and law enforcement. The investigation will determine the initial source of the outbreak, the population at risk, and the epidemiological features of the outbreak. If indicated, this investigation may be performed alongside contact identification and verification activities.

Monitor outcome of confirmed cases

Work with medical providers to monitor the outcome of patients with confirmed smallpox. Report aggregate data to the state epidemiologist or designee.

Contact tracing

The Clinical Guidance for Smallpox Vaccine Use in a Postevent Vaccination Program defines a contact of a smallpox patient as:

• Household family members of the smallpox patient
• Others spending ≥3 hours in the household since the patient's onset of fever
• Non-household members with ≥3 hours of contact <2 meters (<6.5 feet) from a patient with a rash

Start contact tracing activities as soon as possible after a patient has been diagnosed with smallpox.

• Interview the patient – Review the patient's travel history for the previous 2 to 3 weeks. If more people are diagnosed with smallpox, this information will help determine a common source of exposure. Identifying the source of exposure will help to estimate the number of people at risk for illness. Also identify other people the patient has had close contact with since their symptoms began (when the patient became infectious). The interviewers should be vaccinated prior to, or within 72 hours (preferably within 24 hours), of their first contact with the patient and wear appropriate personal protective equipment (PPE). If there is suspicion the smallpox emergency is the result of a deliberate release of the virus, the Federal Bureau of Investigation (FBI) and law enforcement agencies may need to collaborate on these interviews.
• Identify contacts of the patient and their own close household contacts – Interview and assess contacts for symptoms. If any show symptoms of smallpox, arrange for their transport to the healthcare facility in the community designated to care for suspected smallpox cases. As long as those being interviewed do not show symptoms or have a fever, interviewing personnel do not need to wear PPE.
• Vaccinate contacts and their household contacts – Give all contacts and their respective close household contacts information about where and when they can get the smallpox vaccination. Arrange for transportation to the place to receive the vaccination, if necessary. Provide a time and place for a vaccine "take" reading 6 to 8 days after vaccination. Also provide vaccinated contacts with a way to report their temperatures to designated public health officials.
• Monitor vaccinated contacts for 14 to 18 days – Establish a dedicated phone line or other method for vaccinated contacts to report their temperature readings each day (fever surveillance). Contacts who do not have symptoms should take their temperatures twice every day (every 12 hours) for 18 days after their last contact with the smallpox patient, or 14 days after being vaccinated, whichever comes first. Contacts should report their temperatures to the designated public health official daily. If the contact develops a fever ≥101°F (38.3°C) for 2 successive readings, they should notify health department personnel and remain at home until transportation to the healthcare facility in the community designated to care for suspected smallpox cases can be arranged. Designate personnel to follow up with contacts who do not report regularly. Provide contacts information about how to seek care for and report adverse events to vaccination.
• Monitor unvaccinated contacts for 18 days – Any contact or other person deemed as high risk for developing smallpox who refuses vaccination should undergo fever surveillance and remain at home for 18 days after their last known exposure to the smallpox virus.

In a smallpox emergency, the first-line vaccination strategy will be ring vaccination. This strategy was used to successfully eradicate smallpox in the late 20^th century. If there are not enough personnel to trace and vaccinate all contacts quickly enough, public health authorities may augment ring vaccination with a mass vaccination (community-wide) strategy.

The Strategic National Stockpile (SNS) has stockpiled enough smallpox vaccine to vaccinate every person in the United States. In a smallpox emergency, the SNS will coordinate with the Medical Countermeasures (MCM) coordinator or the preparedness office in the state or territorial health department. The MCM coordinator will allocate vaccine to local areas, depending upon the circumstances of the emergency.

Key points for vaccination plans

There are three different smallpox vaccines that each require distinct implementation considerations in a smallpox emergency vaccination strategy: ACAM2000®, APSV, and JYNNEOS^TM (also known as Imvamune or Imvanex). The following highlighted considerations are not comprehensive. Full documentation of vaccine-related clinical information and implementation considerations are found in the Vaccination section for Clinicians. For more information, refer to the Clinical Guidance for Smallpox Vaccine Use in a Postevent Vaccination Program. The Advisory Committee on Immunization Practices (ACIP) is currently evaluating JYNNEOS^TM for the protection of people at risk of occupational exposure to orthopoxviruses in a pre-event setting.

ACAM2000^® and APSV considerations

ACAM2000® is licensed by the U.S. Food and Drug Administration (FDA) and will be used if there is ever a smallpox emergency. APSV has a similar safety profile to ACAM2000® and is also held by the Strategic National Stockpile for use in a smallpox emergency. It will be used under an Emergency Use Authorization (EUA) or Investigational New Drug application (IND) if ACAM2000® is depleted, is not readily available, or on a case-by-case basis for individuals with an allergy to a component of ACAM2000®.

ACAM2000® and APSV are both administered as a single dose by the percutaneous route using the multiple puncture technique. Medical and public health personnel will likely not be familiar with this administration technique, so both advance and just-in-time training will be needed. Training for this unfamiliar method of vaccination may take a couple of hours, even among experienced medical personnel.

Medical personnel with gloved hand administering smallpox vaccine with a bifurcated needle

ACAM2000® and APSV are live virus vaccines containing vaccinia virus. Those vaccinated with either of these vaccines who do not properly care for their vaccination site may spread the vaccinia virus to other parts of their body or to other people, and therefore require vigilant vaccination site care from the day of vaccination until the scab falls off, which usually happens about 14 to 21 days later.

Educate vaccinees on how to care for their vaccination sites properly, what a "take" should look like, and how to seek care for and report any serious adverse events to vaccination. Full immunity is achieved after the confirmation of a "take" 6 to 8 days after vaccination.

JYNNEOS^TM considerations

JYNNEOS is licensed by the FDA for the prevention of smallpox and monkeypox. It is also marketed under the brand names Imvamune and Imvanex in Canada and the European Union, respectively.

The Advisory Committee on Immunization Practices (ACIP) is currently evaluating JYNNEOS^TM for the protection of people at risk of occupational exposure to orthopoxviruses in a pre-event setting. Unlike ACAM2000® and APSV, JYNNEOS^TM is administered subcutaneously as two doses separated by 4 weeks (one dose at week 0 and a second dose at week 4) for primary vaccinees (individuals who have never been vaccinated against smallpox or do not recall receiving a smallpox vaccine in the past). Individuals previously vaccinated against smallpox receive one dose.

Full immunity may not develop until 2 weeks after the second dose (for primary vaccinees). This delay may leave individuals not fully protected for up to 6 weeks after their initial vaccination. Individuals receiving JYNNEOS^TM will need to be especially vigilant to avoid exposure to smallpox patients and the vaccination sites of those vaccinated with ACAM2000® or APSV during the 6 weeks after receiving the first dose and before developing immunity. Smallpox vaccination plans should include ways to ensure these vaccinees return for the second dose.

JYNNEOS^TM does not produce a noticeable "take" like ACAM2000® or APSV. While this means there is no chance of secondary vaccinia transmission with this vaccine, the lack of a noticeable "take" makes it difficult to know whether or not the vaccinee has developed immunity.

Cold chain management

Vaccines should be shipped in a way that maintains the cold chain. ACAM2000® or APSV are shipped refrigerated. JYNNEOS^TM may be shipped and stored either frozen or refrigerated. Cold chain management plans should include the possibility of maintaining the cold chain of vaccines at two different temperatures.

Vaccine supply tracking

Keep accurate counts of vaccine doses given and lost during an outbreak. The SNS and state public health departments will use the information reported by local public health departments to manage the supply and distribution of vaccine during an emergency.

Screening considerations

Because of the high case-fatality rate and severity of smallpox, no clear absolute contraindications exist for the use of smallpox vaccines for those exposed to smallpox virus or at high risk for smallpox infection. Plan for screening potential vaccinees thoroughly, using established criteria. Most people will meet the criteria for vaccination with ACAM2000® or APSV. Clinicians should be available to consult on individuals with a health status that may require using JYNNEOS^TM instead of ACAM2000® or APSV.

Staff vaccination

Staff should be vaccinated, but there is no waiting period between when they receive their vaccination and when they can start administering vaccinations or working in vaccination clinics. To prevent the spread of vaccinia virus from ACAM2000® or APSV, any clinical staff who provide vaccinations or care to patients should follow enhanced vaccination site care methods.

Vaccinee follow-up

For those vaccinated with ACAM2000® or APSV: Identify a time and place for vaccinees to have their vaccination site evaluated. Use the number of people vaccinated and the days on which they were vaccinated to determine the number and timing of staff needed for the follow-up evaluations. Include plans for revaccinating those with non-takes. Follow-up on vaccinees who do not come in for a take evaluation.

For those vaccinated with JYNNEOS^TM Identify a time and place for primary vaccinees to receive their second dose of JYNNEOS^TM, 4 weeks after the first dose. Include plans for following-up on vaccinees who do not come in for their second dose of vaccine.

Adverse event monitoring

While rare, adverse events may happen, especially within a large population of new vaccinees. Give vaccinees information about who to contact or where they can go for medical care if they suspect they are having an adverse event to the vaccination. Consider how to monitor and report these adverse events to public health authorities quickly in overall surveillance plans. Smallpox response plans should also ensure that all adverse events are reported to the Vaccine Adverse Events Reporting System (VAERS).

Countermeasures Injury Compensation Program

The Countermeasures Injury Compensation Program (CICP) is a federal program created to help pay for related costs of medical care and other specific expenses for eligible people seriously injured by the administration or use of certain medical countermeasures. Medical countermeasures may include vaccines, medications, devices, or other items used to prevent, diagnose, or treat the public during a current, or potential future, public health emergency or security threat. For more information, visit the CICP website or call: 1-855-266-2427. In an emergency, provide information about this program to vaccinees.

This strategy vaccinates the contacts of confirmed smallpox patients, and will be the first-line strategy in a smallpox emergency. It also vaccinates people who are in close contact with those contacts. This way, everyone who has been, or could have been, exposed to a patient with smallpox receives the vaccine. Ring vaccination requires thorough and rapid surveillance and epidemiologic case investigation. The Intensified Smallpox Eradication Program used this strategy with great success in its efforts to eradicate smallpox in the latter half of the 20^th century.

In addition to the operational and logistical considerations for vaccination, consider the following in your department's plans for implementing this strategy:

• Decide how to offer the vaccination to identified contacts. For example, do you give contacts referrals to get the vaccination at a designated location? Or do you offer the vaccination at a time and place convenient for the contact?
• Determine how to follow up with the contacts who are vaccinated with ACAM2000® or APSV to evaluate the vaccination site for a "take" (and possibly revaccination, if the vaccinee does not have a visible "take").
• Identify ways to ensure people vaccinated with JYNNEOS return for their second dose (for primary vaccinees).

This strategy vaccinates all eligible and willing people in an area. If there are not enough personnel to trace and vaccinate all contacts quickly enough, public health authorities may choose to implement community-wide, or mass, vaccination campaigns in addition to the ring vaccination strategy. Local public health departments will be responsible for standing up smallpox vaccination clinics in this strategy. Even if mass vaccination campaigns have begun, public health officials should continue ring vaccination to make sure those who have been, or may have been, exposed to a smallpox patient receive the vaccine within a timeframe that will reduce their chances of contracting the disease.

Use existing plans for Points of Dispensing (POD) for other emergencies as a starting point for developing smallpox-specific mass vaccination plans. If you need more information on PODs, refer to the webinar, Mass Dispensing Overview: An SNS Perspective, available online at TRAIN. This hour-long course goes through the necessary details to include in a POD plan.

Emergency plans should address the following points where smallpox vaccination clinics will differ from PODs:

• PODs are designed to dispense medication to the public as quickly as possible. Some plans may allow for head of household pickup or even drive-through dispensing. A smallpox vaccination clinic will require each vaccinee to come to a specific location. The increase in headcount may require additional clinic locations, additional hours of service, or larger locations. All of these changes will affect the number of staff required.
• In addition to the regular staff required for a POD, a smallpox vaccination clinic will require more medically trained staff who will:
  • Screen vaccinees for contraindications
  • Assess vaccinees for which vaccine they should receive (if different vaccines are available)
  • Administer the vaccine
  • Educate the vaccinee on proper vaccination site care (for those receiving ACAM2000® or APSV) or how to decrease the risk of exposure to smallpox before developing immunity (for those receiving JYNNEOS^TM)
• The different vaccines may be shipped at different temperatures (either frozen or refrigerated) and may require separate storage facilities to maintain the cold chain. Work with local and state immunization teams and use existing plans for cold chain management.
• Determine ways to protect vaccinee privacy when screening for which vaccine to use. Consider ways to include private screening areas in the clinic layout. Avoid situations which single out or draw attention to vaccinees who are receiving a replication-deficient vaccine rather than a replication-competent vaccine (for example, JYNNEOS^TM rather than ACAM2000® or APSV) and ensure proper safeguarding of all vaccinees' confidential health information and personal identifying information.
• All vaccine-related waste from a smallpox clinic is classified as Category B hazardous waste. Verify plans for disposal and transport meet local, state, and federal requirements. Educate all clinic staff to follow these guidelines.

Modeling staffing requirements

Two software programs may help plan a smallpox vaccination clinic by modeling different staffing and patient volume options:

• Maxi-Vac Simulation Software – Developed by CDC, Maxi-Vac (2.0) and Maxi-Vac Alternative (2.0) are programs state and local public health officials can use to plan large-scale smallpox vaccination clinics with maximum patient flow-through.
• RealOpt – A program to model mass dispensing and mass vaccination efforts during a pandemic, bioterrorism attack, or radiological disaster. This free program is available for public health or emergency management professionals. RealOpt training is available on TRAIN.

What's new?

Maxi-Vac (2.0) and Maxi-Vac Alternative (2.0) are updated versions of Maxi-Vac and Maxi-Vac Alternative. The updates, made in October 2021, focus on presenting these tools in a spreadsheet-based format. Both the original tools were produced in a Visual Basic format which presented software compatibility issues. The data underlying the calculations and results presented in Maxi-Vac (2.0) and Maxi-Vac Alternative (2.0) remain unchanged.

Overview of Maxi-Vac

The World Health Organization formally declared the eradication of smallpox in May 1980. Following this major public health accomplishment, smallpox vaccinations concluded throughout the world. Although the last recorded natural case of smallpox occurred in 1977, the intentional release of the smallpox virus may be a potentially devastating bioterrorism threat.

To help states and local communities prepare to respond to a potential smallpox attack, the U.S. Centers for Disease Control and Prevention has released generic guidelines on how to set up a smallpox vaccination clinic. However, individual states and communities have differing numbers of qualified personnel that would be available in such an event.

Maxi-Vac (2.0) and Maxi-Vac Alternative (2.0) help a public health official answer the following question: "How can I allocate the limited number of personnel available so that the maximum number of people are vaccinated in a 24-hour period?"

Maxi-Vac uses a mathematical simulation model, assumed time spent in each station, and your input (e.g., the number of personnel available for each shift in a clinic) to optimally allocate personnel and maximize the number of people vaccinated in a clinic during a 24 hour-period. Technical details and other assumptions used in Maxi-Vac (2.0) and Maxi-Vac Alternative (2.0) are provided in the manual.

Getting started with the simulation model

We recommend downloading and saving the spreadsheet tool to your computer so that you can open the spreadsheet from your computer. This will allow the spreadsheet to open in Excel instead of your web browser.

Download the Maxi-Vac tool and user manual

• Maxi-Vac 2.0
• Maxi-Vac Alternative 2.0
• Maxi-Vac 2.0 user manual
• Maxi-Vac Alternative 2.0 user manual

If you encounter any issues with the tool or need assistance with accessibility, please contact HEMU@cdc.gov.

Considerations for using the model

The numbers generated by the tool should not be considered as predictions; rather, they are estimates of what could happen given the user input and assumptions.

You are encouraged to run the model several times. Once you are comfortable using the tool, you may wish to consider a plan wherein you systematically alter the values of input variables. You may alter one variable at a time (univariate sensitivity analysis) or alter the values of two or more variables simultaneously (multivariate sensitivity analysis).

Differences between Maxi-Vac and Maxi-Vac alternative

Between the two tools, there are differences in the number of personnel that a user can select (i.e., how many physicians, nurses, and other non-medical staff can be selected) in the stations of the mass vaccination clinic (i.e., the size of the orientation room, the need for orientation and/or witnesses), and the percentage of families that need more detailed pre-vaccination medical screening. Processing times at the stations vary between the two versions. See the manual for more details on the specific differences.

Which version should I use?

Each public health unit is likely to face unique circumstances when standing up vaccination clinics. You are strongly encouraged to examine the differences between Maxi-Vac (2.0) and Maxi-Vac Alternative (2.0) before deciding which version to use. Maxi-Vac (2.0) may be best suited for larger vaccination clinics as it allows for more staff and larger orientation rooms, while Maxi-Vac Alternative (2.0) may be better suited to see how potentially optional stations affect the flow of people vaccinated in a 24-hour period. In addition, Maxi-Vac Alternative (2.0) assumes a much shorter processing time in the orientation, medical screening, and physician evaluation stations. It also possible to use both versions of the tool and compare results between versions to get a range of people vaccinated, instead of a precise number. Results from both models should not be viewed as definitive, but rather as a guide to the first steps in planning such clinics.

Disclaimer

Please keep in mind that the numbers generated should not be considered predictions of what will occur while running a mass immunization clinic. Rather, they are estimates of what could happen. The findings and conclusions of this manual and software are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.