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Antiviral Drug Priority Group Recommendations
1. Persons admitted to hospital with influenza infection

a) Definition
Persons admitted to acute care facilities (traditional or non-traditional with a clinical diagnosis of influenza; laboratory confirmation not required). Excludes persons admitted for a condition consistent with a bacterial superinfection (e.g., lobar pneumonia developing late after illness onset) or after viral replication and shedding has ceased (e.g., as documented by a negative sensitive antigen detection test)

b) Strategy
Treatment within 48 hours of symptom onset. (10 capsules)

c) Rationale
This group is at greatest risk for severe morbidity and mortality. Although there are no data to document the impacts of antiviral drug treatment among persons who already suffer more severe influenza illness, benefit is biologically plausible in persons with evidence of ongoing virally mediated pathology (e.g., diffuse pneumonia, ARDS). Providing treatment to those who are most ill is also consistent with standard medical practices, would be feasible to implement, and would be acceptable to the public.

d) Population size
The number of persons admitted to hospital in an influenza pandemic would vary substantially depending on the severity of the pandemic and on the ability to expand inpatient capacity, if needed.

e) Unresolved issues
More specific guidance should be provided to healthcare workers on implementing antiviral treatment, including when and when not to treat. In some persons with severe illness, the ability to take oral medication or its absorption may be important issues. For infants <1 year old admitted to hospital, decisions about whether to treat with antiviral drugs may depend on the child’s age and potential risk versus benefit as the neuraminidase inhibitors are not licensed for use in infants. If possible, data on time from symptom onset to hospital admission, current use of antiviral drug treatment among inpatients, and its impacts should be collected during interpandemic influenza seasons.

2. Healthcare workers and emergency medical service providers who have direct patient contact

a) Definition
Persons providing direct medical services in inpatient and outpatient care settings. Includes doctors, nurses, technicians, therapists, EMS providers, laboratory workers, other care providers who come within 3 feet of patients with influenza, and persons performing technical support functions essential to quality medical care.

b) Strategy
Treatment within 48 hours of symptom onset. (10 capsules)

c) Rationale
Maintaining high quality patient care is critical to reduce health impacts of pandemic disease and to prevent adverse outcomes from other health conditions that will present for care during the pandemic period. Treatment of healthcare providers will decrease absenteeism due to influenza illness and may decrease absenteeism from fear of becoming ill, given the knowledge that treatment can prevent serious complications of influenza. Good data exist documenting the impacts of early treatment on duration of illness and time off work, and on the occurrence of complications such as lower respiratory infections. Treating healthcare providers is feasible to implement, especially for inpatient care providers who can be provided drugs through the occupational health clinic. It also would be acceptable to the public, who would recognize the importance of maintaining quality healthcare and would understand that persons with direct patient contact are putting themselves at increased risk.

d) Population size
There are about 12.6 million persons designated as healthcare workers by the Bureau of Labor Statistics and about 820,000 EMS providers. Among HCWs, two-thirds are estimated to provide direct patient care services.

e) Unresolved issues
Further work is needed to hone definitions and estimate population sizes. Implementation issues include the approach to identifying healthcare providers who would be eligible for treatment and where the treatment would be provided, particularly for outpatient care providers.

3.Outpatients at highest risk for severe morbidity or mortality from influenza infection

a) Definition
The Advisory Committee on Immunization Practices defines groups at high risk (or increased risk) of complications from influenza infection during annual outbreaks based on age (6-23 months and >65 years) and underlying illnesses. Among this population of about 88 million persons, some can be identified who are at highest risk of severe disease and death. These include persons with hematopoetic stem cell transplants (HSCT) and solid organ transplants; those with severe immunosuppression due to cancer therapy or hematological malignancy; persons receiving immunosuppressive therapy for other illnesses (e.g., rheumatoid arthritis); persons with HIV infection and a CD4 count <200; persons on dialysis; and women who are in the second or third trimester of pregnancy.

b) Strategy
Treatment within 48 hours of symptom onset. (10 capsules)

c) Rationale
Of the large group of persons who are at increased risk of severe disease or death from influenza, these groups represent the population at highest risk and who are least likely to be protected by vaccination. Studies show that neuraminidase inhibitor therapy decreases complications and hospitalizations from influenza in high-risk persons and one unpublished study shows a significant decrease in mortality among patients who have undergone a hematopoteic stem cell transplant.

d) Population size
About 150,000 persons have had an HSCT or solid organ transplant. Assuming that the period of severe immunosuppression after a cancer diagnosis lasts for 1 year, the population targeted with non-skin, non-prostate cancers would equal the incidence of about 1.35 million persons. Based on a birth cohort of 4.1 million, a 28-week risk period during the second and third trimesters, and an 8-week pandemic outbreak in a community, there would be about 400,000 pregnant women included in this risk group. Further work is needed to estimate the size of other immunosuppressed groups.

e) Unresolved issues
Specific definition of included groups and population sizes.
4. Pandemic health responders, public safety workers, and key government decision-makers

a) Definition

Public health responders include those who manufacture vaccine and antiviral drugs; persons working at health departments who are not included as healthcare workers; and those who would be involved in implementing pandemic vaccination or other response components. Public safety workers include police, fire, and corrections personnel. Key government decision-makers include chief executives at federal, state, and local levels.

b) Strategy
Treatment within 48 hours of symptom onset. (10 capsules)

c) Rationale
Preventing adverse health outcomes and social and economic impacts in a pandemic depend on the ability to implement an effective pandemic response. Early treatment of pandemic responders will minimize absenteeism and ensure that vaccination and other critical response activities can be maintained. Implementing early treatment for public health workers and vaccine manufacturers is feasible at workplace settings. Public safety workers prevent intentional and unintentional injuries and death, are critical to maintaining social functioning, and will contribute to a pandemic response, for example by ensuring order at vaccination clinics. A small number of decision-makers at federal, state, and local levels are needed to for an effective pandemic response.

d) Population size
An estimated 40,000 workers who produce pandemic vaccine and antiviral drugs in the U.S.; ~300,000 public health workers who would not be included in the HCW category; 3 million public safety workers; and a small number of government decision-makers.

e) Unresolved issues
Need to define the exact composition and size of this group.

5. Outpatients at increased risk of severe morbidity or mortality from influenza

a) Definition
For planning purposes, this group would include those currently designated as high-risk groups, except for those who have been categorized as being at highest-risk and included in a separate category. This increased-risk group includes persons 6-23 months and >>65 years old, or who have underlying illnesses defined by the ACIP as associated with increased risk. Definition of this group may change based on the epidemiology of the pandemic.

b) Strategy
Treatment within 48 hours of symptom onset. (10 capsules)

c) Rationale
Early treatment has been shown to significantly decrease lower respiratory infections and to reduce the rate of hospitalization in elderly and high-risk populations. By extrapolation and based on the results of one small uncontrolled study, significant reductions of mortality can be expected as well. As these risk groups are familiar to the public given recommendations for annual vaccination, communication would be easy and acceptability high.

d) Population size
About 85.5 million persons are included in this group. Although all are at increased risk of annual influenza compared with the healthy under-65 year old population, there are different levels of increased risk for severe complications and death within this category. Further stratification may be possible based on several parameters including number of underlying conditions; recent hospitalization for a high-risk condition, pneumonia, or influenza; and age.

e) Unresolved issues
Stratifying this group into those at greater and lesser risk may be important if antiviral supplies are limited. Implementing treatment will be challenging given that it should be provided at the initial point of care to accrue the greatest benefit from early therapy.

6. Outbreak control

a) Definition
Use of antiviral drugs to support public health interventions in closed settings where an outbreak of pandemic influenza is occurring.

b) Strategy
Treatment of cases and post-exposure prophylaxis of contacts (once daily antiviral medication for 10 days).

c) Rationale
Influenza outbreaks in nursing homes are associated with substantial mortality and morbidity. Nursing home residents also are less likely to respond to vaccination. Post-exposure prophylaxis has been shown to be effective in stopping influenza outbreaks in closed settings.

d) Population size
The number of outbreaks that may occur during a pandemic is unclear. Measures should be implemented to prevent outbreaks including limiting visitors, vaccination of staff, furloughing non-critical staff, and screening and exclusion for illnesses consistent with influenza.

e) Unresolved issues
Should this policy also be implemented in prisons or other settings where explosive spread of illness may occur but the risk for severe complications is not high?

7. Healthcare workers in ER, ICU, EMS, and dialysis settings

a) Definition
Includes all staff in these settings who are required for effective functioning of these health care units.

b) Strategy
Prophylaxis (40 capsules)

c) Rationale
Optimally effective functioning of these units is particularly critical to reducing the health impacts of a pandemic. Prophylaxis will minimize absenteeism in these critical settings.

d) Population size
Need to obtain population estimates.

e) Unresolved issues
Population sizes

8. Pandemic societal responders and healthcare workers who have no direct patient contact

a) Definition
This group includes persons who provide services that must be sustained at a sufficient level during a pandemic to maintain public well-being, health, and safety. Included are workers at healthcare facilities who have no direct patient contact but are important for the operation of those facilities; utility (electricity, gas, water), waste management, mortuary, and some transport workers.

b) Strategy
Treatment within 48 hours of symptom onset.(10 capsules)

c) Rationale
Maintaining certain key functions is important to preserve life and decrease societal disruption. Heat, clean water, waste disposal, and corpse management all contribute to public health. Ensuring functional transportation systems also protects health by making it possible for people to access medical care and by transporting food and other essential goods to where they are needed.

d) Population size
Within these broad categories, there are about 2 million workers at healthcare facilities who have no direct patient contact; 730,000 utility workers; 320,000 waste management workers; 62,000 in mortuary services; and 2.3 million in transportation. Not all occupations within these categories would be classified as pandemic societal responders. Estimates are that 35% of this population will develop illness and present within 48 hours of onset regardless of pandemic severity.

e) Unresolved issues
Need to stratify within these groups to identify who fills specific pandemic societal response functions and to assess whether those functions could still operate if a substantial proportion of the workforce became ill during a 6-8 week pandemic outbreak within a community. Implementation issues need to be addressed, especially with respect to how persons would be identified as falling within this priority group when presenting for treatment and where that treatment would be provided.

9. Other outpatients

a) Definition
Includes persons not in one of the earlier priority groups.

b) Strategy
Treatment within 48 hours of illness onset. (10 capsules)

c) Rationale
Treatment reduces the risk of complications and mortality, reduces duration of illness and shortens time off work, and decreases viral shedding and transmission. If sufficient antiviral supplies are available, providing treatment to all who are ill achieves equity and will be most acceptable to the public.

d) Population size
There are an estimated 180 million persons who are not included in previously targeted groups.

e) Unresolved issues
Consider whether there are any strata that can be defined within this population.
Note: a chart of the priority groups on pg. D-21 contains the following 2 groups that were not accounted for in the the wider explanations listed above:

Highest Risk Outpatients:
Definition: Unknown
Strategy: Prophylaxis (40 capsules)
Rationale: Prevents illness in the highest risk groups
for hospitalization and death
Population: Estimated 2.5 million
Unresolved issues: Unknown

Other Health Care Workers with direct patient contact
Definition: Unknown
Strategy: Prophylaxis (40 capsules)
Rationale: Prevention would best reduce absenteeism
and preserve optimal function.
Population: Estimated 8 million
Unresolved issues: unknown

C. Additional NVAC recommendations on antiviral drugs for pandemic influenza :

In addition to recommendations for priority groups, NVAC unanimously adopted the following recommendations:
Sufficient drugs should be stockpiled to address top priorities. NVAC recommends that the minimum stockpile size be about 40 million courses, allowing coverage of the top 7 priority groups.
Oseltamivir should be the primary drug stockpiled, but some zanamivir also should be obtained as it is effective against some oseltamivir-resistant strains, may be preferred for treatment of pregnant women, and supporting two manufacturers enhances security against supply disruptions. Approximately 10% of the stockpile should be zanamivir if feasible and cost effective. No additional adamantanes should be stockpiled.
Antiviral drugs can also be used as part of an international effort to contain an initial outbreak and prevent a pandemic. Use to slow disease spread early in a pandemic may be useful but requires large amounts of drug.
Critical research should be conducted to support development and implementation of recommendations for pandemic influenza antiviral drug use, including:
Impact of treatment at hospital admission on outcome
Optimal treatment dose for H5N1 and other potential pandemic strains
Sensitivity and use of rapid diagnostic tests for H5N1 and other influenza strains with pandemic potential
Safety and pharmacokinetics of oseltamivir among infants <1 year old
Investigation of the impact of other drugs (new antiviral agents and other classes such as statins) on influenza
Additional work with public and private sector groups should be done to further hone definitions of target groups and their estimated population sizes, and to provide further guidance on antiviral drug distribution and dispensing.