Interim Guidance for Follow-up of Close Contacts of Persons Infected with Novel Influenza A Viruses Associated with Severe Human Disease or with Potential to Cause Severe Human Disease, and Use of Antiviral Medications for Post-exposure Prophylaxis

Overview

This interim guidance is based on expert opinion and currently available published and unpublished data for antiviral treatment and chemoprophylaxis of seasonal, pandemic, and novel influenza A virus infections. These recommendations are based on the following considerations:

• Novel influenza A viruses have caused sporadic infections of wide clinical severity, and some [e.g. highly pathogenic avian influenza A(H5N1) and A(H5N6) viruses, and avian influenza A(H7N9) virus] have resulted in severe human disease and substantial mortality to date.
• Limited, non-sustained human-to-human transmission of some novel influenza A viruses associated with severe human disease likely occurred or cannot be excluded in some human case clusters that have occurred in the past worldwide.
• Sufficient supplies of influenza antiviral medications that are expected to be effective against novel influenza A viruses are available.

The public health goal of this interim guidance is to reduce the risk of human-to-human spread of novel influenza A viruses from infected persons in the United States. It is specific to a scenario in which there are sporadic cases of human infections associated with exposures to infected domestic poultry, wild birds, dairy cows, or other infected animals.

Definition of Close Contacts

Close contacts are defined as persons with close (within 6 feet) within a room or care area or other enclosed space (e.g., vehicle), who had unprotected (without use of recommended personal protective equipment) exposure to a person who is a symptomatic confirmed or probable human case of novel influenza A virus infection for a prolonged period of time, or who had direct contact with infectious secretions while the case-patient was likely to be infectious (beginning 1 day prior to illness onset and continuing until resolution of illness).

In general, decisions to begin antiviral post-exposure prophylaxis should be guided by the risk stratification described below based on observational data for reported cases of human infections with avian influenza A(H7N9) and A(H5N1) viruses, and on data from seasonal influenza studies. The risk of infection following close contact with a confirmed or probable novel influenza A case-patient is higher for persons with prolonged, unprotected exposures (e.g., without use of respiratory and eye protection) than for close contacts (e.g., health care personnel) who were wearing recommended personal protective equipment.

Table. Risk by exposure to inform clinical decision-making

The purpose of this table is to help clinicians and public health practitioners to categorize the risk for novel influenza A virus infection among exposed human close contacts of symptomatic¹ confirmed or probable cases of human infection with novel influenza A virus, to inform decisions about prescription of antiviral post-exposure prophylaxis to close contacts. This risk stratification table is for clinical purposes and differs from other tables that provide a framework for epidemiologic assessment of individual risk for novel influenza A virus infection for use by public health practitioners to help determine how best to prioritize monitoring and investigation efforts when resources are limited.

1. Confirmed and probable cases whose symptom status was unknown at the time of exposure should be treated as symptomatic for purposes of follow up and management of close contacts.
2. Household members who have prolonged unprotected close contact to a symptomatic person with confirmed or probable novel influenza A virus infection may be at higher risk of exposure and infection than others because of the duration of exposure in a closed setting.
3. Health care personnel with prolonged unprotected close contact to a symptomatic person with confirmed or probable novel influenza A virus infection may be at higher risk of infection than others through caring for patients with severe illness who may have levels of virus in the respiratory tract.
4. Persons with prolonged unprotected close contact to a symptomatic person with confirmed or probable novel influenza A virus infection and mild illness may have a higher risk of infection than those with short duration of exposure.
5. Persons with prolonged, unprotected close contact to a symptomatic person with confirmed or probable human infection with a novel influenza A virus outside of a room or other enclosed space have an unknown risk of infection and need to be evaluated on a case-by-case basis.
6. Laboratory personnel with unprotected direct or close exposure to a person with confirmed or probable novel influenza A virus infection have an unknown risk of infection depending upon the specific exposures and need to be evaluated on a case-by-case basis.

Follow-up of Close Contacts of a Novel Influenza A Case-Patient

Public health personnel should attempt to identify as soon as possible and monitor all close contacts of symptomatic confirmed or probable cases of human infection with novel influenza A viruses associated with severe or potentially severe human disease for new illness.

• Identified close contacts should be monitored daily for illness for 10 days after the date of the last known exposure to a symptomatic confirmed or probable case.
• Measured temperature and presence of acute respiratory symptoms should be assessed daily during this period.
• Any close contacts of a symptomatic confirmed or probable case who develop any new illness signs or symptoms, especially respiratory symptoms (e.g., cough, sore throat, shortness of breath, difficulty breathing), conjunctivitis, or other symptoms, with or without fever (see clinical criteria) should be referred for prompt medical evaluation and testing for novel influenza A virus infection.
• To facilitate investigation, and if resources are available, close contacts of suspected cases (especially those with a high index of suspicion) also may be identified and monitored for any new illness signs or symptoms, especially respiratory symptoms (e.g., cough, shortness of breath, difficulty breathing), conjunctivitis, or other symptoms, with or without fever, while the results of laboratory testing are pending.

Rationale for duration of monitoring of close contacts of a novel influenza A case-patient

Available data suggest that the estimated incubation period for human infection with avian influenza A(H5N1) and A(H7N9) viruses is generally 3 to 5 days, but has been reported to be 7-10 days 123456789101112. Limited non-sustained person-to-person transmission of A(H7N9) virus could not be excluded in some family clusters 7 . Limited non-sustained person-to-person transmission of A(H5N1) virus has been reported in several countries following close, prolonged unprotected contact with a severely ill A(H5N1) patient, including in household and hospital settings 61011.

Post-exposure Antiviral Prophylaxis of Asymptomatic Close Contacts

Oral oseltamivir post-exposure prophylaxis should be provided to close contacts of a symptomatic confirmed or probable novel influenza A case-patient as soon as possible according to risk of exposure.

• In highest-risk exposure groups, post-exposure prophylaxis should be administered.
• In moderate-risk exposure groups, post-exposure prophylaxis can be considered on a case-by-case basis.
• In low-risk exposure groups, post-exposure prophylaxis is not routinely recommended.

Decisions to begin antiviral post-exposure prophylaxis for persons in moderate- and low-risk exposure groups should be based on clinical judgment, with consideration given to the type of exposure and to whether the close contact is at higher risk for complications from influenza.

• Antiviral post-exposure prophylaxis should begin as soon as possible (ideally within 48 hours) after the first exposure to the symptomatic confirmed or probable case.
• Oral oseltamivir at treatment dosing frequency (one dose twice daily) is recommended instead of the typical antiviral chemoprophylaxis regimen (once daily) for seasonal influenza. All human infections with highly pathogenic avian influenza A(H5N1) virus in the U.S. have been with viruses susceptible to oseltamivir.
• Antiviral post-exposure prophylaxis with oseltamivir (twice daily) should be continued for 5 or 10 days. If the exposure was time-limited and not ongoing, the recommended duration is 5 days from the last known exposure. If the exposure is likely to be ongoing (e.g., household setting), a duration of 10 days is recommended because of the potential for prolonged infectiousness from the novel influenza A case-patient.

• Specific dosage recommendations for treatment by age group are available at Recommended Dosage and Duration of Influenza Antiviral Medications for Treatment or Chemoprophylaxis. Refer to the treatment dosing (twice daily) as provided for seasonal influenza.
  • This recommendation for oral oseltamivir with twice daily antiviral post-exposure prophylaxis dosing is based on limited data in animals that support higher chemoprophylaxis dosing for avian influenza A(H5N1) virus infection 13, and on the desire to reduce the potential for development of antiviral resistance while receiving once daily chemoprophylaxis 141516.
  • To support post-exposure prophylaxis with oseltamivir using twice daily dosing for novel influenza A viruses associated with severe human disease, including highly pathogenic avian influenza A(H5N1) virus, CDC issued Emergency Use Instructions (EUI) for oseltamivir.

Antiviral Treatment of Symptomatic Close Contacts

• Close contacts of a symptomatic confirmed or probable novel influenza A case-patient who develop any new respiratory symptoms (e.g., cough, sore throat, shortness of breath, difficulty breathing), conjunctivitis, or other symptoms, with or without fever (see clinical criteria) should be promptly tested for novel influenza A virus infection).
• Close contacts of a symptomatic confirmed or probable novel influenza A case-patient who develop any new respiratory symptoms (with or without fever) and who are not receiving antiviral post-exposure prophylaxis should receive empiric antiviral treatment as soon as possible with oral oseltamivir. More antiviral information is available at Interim Guidance on the Use of Antiviral Medications for Treatment of Human Infections with Novel Influenza A Viruses Associated with Severe Human Disease.)
• Symptomatic persons should be isolated at home except to seek medical care and advised to avoid contact with other persons until their illness is resolved.

New Symptoms in close contacts after Use of an Antiviral Agent

• If a close contact develops respiratory symptoms or has worsening of symptoms after or during use of an influenza antiviral medication, contact with other persons should be minimized and appropriate infection prevention and control measures should be used in healthcare settings. More information is available at Interim Guidance for Infection Control Within Healthcare Settings When Caring for Patients with Confirmed Cases, Probable Cases, and Cases Under Investigation for Infection with Novel Influenza A Viruses Associated with Severe Disease).
  • A newly symptomatic close contact should have an initial respiratory specimen collected promptly and sent to the state public health department for novel influenza A virus testing, and potentially for antiviral resistance testing.
  • A previously symptomatic close contact with worsening of symptoms should have a second respiratory specimen collected promptly and sent to the state public health department for novel influenza A virus testing, and potentially for antiviral resistance testing.

• If a close contact tests positive for a novel influenza A virus associated with severe disease in humans (e.g., A(H5N1), A(H5N6) or A(H7N9) virus) and had taken oseltamivir post-exposure prophylaxis for 3 or more days before becoming symptomatic 17, oseltamivir should be stopped as soon as treatment with inhaled zanamivir (twice daily) or oral baloxavir can be initiated. This is because some novel influenza A viruses may rapidly become oseltamivir-resistant (and potentially peramivir-resistant) and remain zanamivir-susceptible and baloxavir-susceptible.
• Investigation for antiviral resistance should be initiated immediately (in conjunction with the CDC Influenza Division), and infection prevention and control measures recommended for patients with novel influenza A virus infection should be implemented. More information is available at Interim Guidance for Infection Control Within Healthcare Settings When Caring for Confirmed Cases, Probable Cases, and Cases Under Investigation for Infection with Novel Influenza A Viruses Associated with Severe Disease.)
• Questions regarding arranging testing for antiviral resistance, or regarding appropriate clinical management if antiviral resistance is a concern, should be directed to the CDC Influenza Division via the CDC Emergency Operations Center (770-488-7100).