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Keywords:

  • Guidelines;
  • immunosuppression;
  • pandemic

Abstract

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References

Novel influenza A/H1N1 virus has caused significant illness worldwide. In response to this global crisis, the American Society of Transplantation (AST) Infectious Diseases Community of Practice and the Transplant Infectious Diseases section of The Transplantation Society (TTS) developed a guidance document for novel H1N1. In this paper, we discuss current guidance for H1N1 as it relates to solid organ transplantation. We include discussion around clinical presentation, diagnosis, therapy and prevention specifically addressing areas such as chemoprophylaxis, immunization and donor-derived infection. Although this document addresses conditions specific to novel H1N1, many principles could be applied to future pandemics. As new information emerges about novel H1N1, updates will be made to the electronic version of the document posted on the websites of the AST and TTS.


Background and Significance

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References

Influenza A and B are common causes of viral infections each year in transplant recipients, with predictable complications including viral pneumonia, secondary bacterial pneumonia and possibly acute allograft rejection in the setting of weaning of immunosuppression (1). Annual vaccination with seasonal trivalent influenza vaccine for recipients as well as close contacts is the standard of care in most transplant centers.

In April 2009, a novel influenza A (H1N1) virus was initially detected in two children in the United States and subsequently determined to be the cause of outbreaks of disease in Mexico; within 2 months, infection had spread worldwide, causing the World Health Organization (WHO) to declare a pandemic on June 11, 2009. Infection has been noted to be most common in the young, with particularly severe disease in pregnancy and presumably in more traditional high-risk groups for influenza infection, including transplant candidates and recipients. Although initially effective against this novel H1N1 strain, oseltamivir resistance was noted in two immunocompromised patients in August 2009 (2). Reassortment with seasonal human influenza A strains and potentially with H5N1, with unpredictable virulence is a significant concern. Recent data show that in persons born before 1950, there is a potential for cross-reactive antibodies to novel H1N1 in 34% (3).

Reaction to this novel respiratory virus in the transplant community has been swift, with concern for prevention, diagnosis and treatment of infection as public health data mount and the course of the pandemic evolves. The International Society for Heart and Lung Transplantation has developed guidelines for heart and lung transplant recipients in the pandemic setting, raising concern for transmission of novel H1N1 infection from thoracic organ donors (4).

Animal and human autopsy studies have demonstrated that acute influenza A infection in the immunocompetent host may result in infection of multiple organs, including the brain, kidney, pancreas, spleen, liver and heart, in addition to the lungs (5–8). This has implications for potential donor transmission for transplant types other than lung. Overall, the impact of infection in potential donors (living and deceased), in those waiting on the transplant list with endstage organ disease, and in those having undergone transplantation has implications for donor selection, peritransplant management and the care of the transplant recipient.

The Infectious Diseases Community of Practice of AST and the Transplant Infectious Disease section of The Transplantation Society have developed the following guidelines for the prevention, diagnosis and treatment of novel H1N1 influenza A infection in the solid organ transplant (SOT) setting, using available data on current patterns of infection, reports of resistance, and what is already known about the control of influenza. The guidelines will be updated as new data become available. Updates will be posted on the AST and TTS websites.

Diagnosis of Novel Influenza A/H1N1

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References
  • • 
    H1N1 should be suspected when patients present with flu-like symptoms (i.e. temperature ≥37.8°C, and cough and/or sore throat) and have suspected or confirmed evidence of exposure to H1N1 virus. This could include specific exposure to a confirmed case or evidence of H1N1 activity in the community. Novel H1N1 may also be associated with gastrointestinal symptoms such as nausea, vomiting and diarrhea in up to a third of cases. Atypical presentations may occur in those with significant immunosuppression and/or lymphopenia (e.g. fever with no other symptoms or an afebrile patient with rhinorrhea alone).
  • • 
    We recommend confirming a diagnosis by specific testing when H1N1 is suspected in a transplant patient. This includes patients with influenza-like illness and those with milder symptoms such as rhinorrhea if contact with novel H1N1 has occurred.
    • ○ 
      Suspected cases of H1N1 are defined as those occurring in patients who have signs and symptoms consistent with influenza and potential exposure to H1N1 (i.e. presence of H1N1 activity in the community or exposure within the prior 7 days to a confirmed or probable case) in the absence of another defined cause of symptoms.
    • ○ 
      Probable cases are patients who have flu-like symptoms, positive testing for influenza A and negative for seasonal H1 and H3 by influenza reverse transcriptase polymerase chain reaction (RT-PCR).
    • ○ 
      Confirmed cases require confirmation of the presence of novel H1N1 (2009) by real-time RT-PCR or viral culture (9).
  • • 
    Appropriate samples for testing include nasopharyngeal swab with or without an oropharyngeal swab, or a nasal aspirate. Endotracheal aspirates from intubated patients, bronchoalveolar lavage specimens and sputum specimens may also be used. All specimens should be promptly placed in sterile viral transport media and kept at 4°C for transport to the microbiology laboratory (10).
  • • 
    Specific testing for H1N1 by standard methodology should be performed using real-time reverse transcriptase polymerase chain reaction (RT-PCR) or other nucleic acid based detection assay whenever possible. Samples that are positive for influenza A and negative for seasonal H1 and H3 can be further tested at the CDC or state laboratories for definitive confirmation as H1N1.
  • • 
    If RT-PCR is not available, rapid antigen detection may be acceptable for point of care testing, although will have lower sensitivity (estimated to range from 10% to 51%) and will not differentiate novel H1N1 from other strains of influenza A. Consequently, negative rapid tests cannot exclude the diagnosis (11).
  • • 
    Immunofluorescence by direct or indirect assays can also identify influenza A but will not differentiate novel H1N1 strains from seasonal influenza, In addition, the rapid kits have variable sensitivity for novel H1N1; accordingly, a patient with a negative test must have further testing with more a sensitive method (11,12).
  • • 
    Specific instructions on collection of appropriate specimens for testing are available at http://www.a-s-t.org/files/pdf/ast_h1n1_guidance.pdf.

Treatment of Novel Influenza A/H1N1

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References
  • • 
    The viral dynamics of seasonal influenza have been well studied among hematopoietic stem cell transplant recipients and prolonged viral replication, even in the setting of active antiviral therapy has been shown (13). Similar studies have not been conducted in SOT recipients.
  • • 
    Lymphocyte depletion as well as enhanced immune suppression, particularly high doses of steroids, are likely to prolong viral replication (14). Viral replication of novel influenza A/H1N1 is predicted to be prolonged in transplant recipients.
  • • 
    As such, the optimal duration of therapy for influenza has not been well established but courses longer than the currently approved 5 days may be needed. Some experts recommend continuing antiviral therapy until viral replication has ceased (e.g. check PCR once a week and treat until negative). Duration of therapy should be guided based on current CDC treatment recommendations and individualized patient assessments. Lung transplant patients with impaired lung function may need longer treatment than other organ transplant recipients.
  • • 
    As recommendations on therapy may change over time, consult the CDC antiviral therapy page prior to selecting antiviral therapy http://www.cdc.gov/h1n1flu/recommendations.htm (15).
  • • 
    In healthy individuals, use of antiviral agents has not been found to be beneficial if symptoms have been present for more than 48 h. Contrary to this, there is likely to be benefit in treating symptomatic SOT recipients with evidence of viral replication (positive culture, rapid antigen or PCR-based testing), even if symptoms have extended beyond 48 h. Treatment of all transplant patients is recommended regardless of the duration of symptoms (Table 1).
  • • 
    Empiric antiviral therapy should be considered in SOT recipients in whom symptoms are suggestive of novel influenza A/H1N1 (also see ‘Diagnosis of Novel Influenza A/H1N1’ section). All attempts must be made to confirm a diagnosis, however.
  • • 
    Prolonged shedding has been noted in SOT recipients with novel influenza A/H1N1 (14).
  • • 
    Data on treating the recipient who is asymptomatic at the time of diagnosis are not available. Clinical judgment should be used.
  • • 
    Currently, wild-type novel H1N1 is resistant to both M2 inhibitors (amantadine and rimantadine) and this class should not be used as monotherapy. All wild-type novel H1N1 are susceptible to all approved (oseltamivir and zanamivir) and investigational (peramivir) neuraminidase inhibitors. A number of novel H1N1 viruses have been described to have developed resistance to oseltamivir secondary to a mutation, typically at position 275, over the course of therapy (17). These strains have typically continued to be susceptible to zanamivir. If cocirculation of neuraminidase-inhibitor resistant influenza occurs, combination therapy with both a M2 inhibitor and oseltamivir or zanamivir monotherapy may be indicated.
  • • 
    Intravenous antiviral therapy may be considered in those individuals who are severely ill and have progressed despite oral therapy or in whom there is concern about the absorption of oral therapies. Alternatively, some experts recommend that the dose of oseltamivir may be doubled (e.g. increased to 150 mg b.i.d.) in critically ill adult patients. In patients with significant disease, a reduction in immunosuppression is recommended.
  • • 
    Currently, there are two investigational IV antiinfluenza antivirals: peramivir and zanamivir. An Emergency Use Authorization has recently been issued for peramivir (see website for details: http://www.cdc.gov/h1n1flu/eua/peramivir.htm), which facilitates access to this antiviral. IV zanamivir is available via compassionate use request and required the site to file an eIND with the FDA.
  • • 
    Patients with viral replication beyond 7–10 days despite active antiviral therapy or progression of symptoms despite therapy should raise the concern for antiviral resistance. There are few reference laboratories that can do resistance testing; optimally testing should include screening for more than just the presence of the H275Y mutation.
  • • 
    Ongoing studies: Currently, there are a number of antivirals and antiviral combinations that are undergoing investigation and/or are available for compassionate use. These are listed and will be updated periodically at http://www.a-s-t.org/files/pdf/ast_h1n1_guidance.pdf.
Table 1.  CDC-recommended doses of oseltamivir and zanamivir
DrugTreatment dose1Dose adjustment
CrCl (mL/min)Dose
  1. CrCl, creatinine clearance.

  2. 1Dose recommended in normal renal function. Some experts recommend consideration of higher doses of these agents (typically twice the approved dose) as registration studies demonstrated a trend toward increased antiviral activity with similar toxicity profiles (16).

  3. 2There are limited data on the safety and tolerability of zanamavir in lung transplant recipients. Also, there is limited systemic exposure of the drug. The clinical significance of this is unknown.

  4. 3No treatment or prophylaxis dosing recommendations are available for patients undergoing renal dialysis.

Zanamivir2Two puffs (10 mg) twice dailyNo dose adjustment needed 
Oseltamivir75 mg twice dailyCrCl < 30375 mg once daily

Routine Chemoprophylaxis and Postexposure Prophylaxis

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References
  • • 
    Based on concerns about drug resistance, chemoprophylaxis with oseltamivir for the duration of the pandemic is not routinely recommended but can be considered for select patients. Prophylaxis may be considered for recent transplant recipients, those who have recently received lymphocyte-depleting antibodies, and those in whom immunization is contraindicated.
  • • 
    A SOT recipient who has had known exposure to novel Influenza A/H1N1 should be counseled to watch for early signs and symptoms of influenza. A prescription can be given (with treatment doses of antivirals) and treatment initiated with early signs and symptoms.
  • • 
    Alternatively, the transplant patient who has been exposed can receive chemoprophylaxis to complete 10 days from the day of last known exposure (see doses for children in pediatric section). However, cases of oseltamivir resistance have occurred in the setting of patients receiving prophylaxis.

Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References

Recommendations for individual patients and family

  • • 
    Avoid contact with individuals who are known to have been diagnosed with influenza.
  • • 
    Strict hand washing or hand hygiene (use of alcohol-based hand gels), particularly after coughing or sneezing, should be performed as this is an effective way to decrease the risk of contracting H1N1.
  • • 
    Practice cough etiquette; cover the nose and mouth with a tissue when coughing or sneezing, and throw the tissue in the trash after use. If no tissue is available, the person should cough or sneeze into their sleeve to avoid contaminating their hands.
  • • 
    Visits for routine well health checks and diagnostic tests to a health care facility should be limited during epidemic periods.
  • • 
    Vaccinations should be obtained when available from your health care provider or health department for both seasonal influenza and for novel H1N1.
  • • 
    There are no general restrictions for SOT patients with regards to travel.

Recommendations for health care providers/ immunization

  • • 
    Health care workers should remain off work and not have contact with patients if they have symptoms of influenza-like illness.
  • • 
    Transplant programs should communicate with SOT candidates and recipients outlining precautions with regards to H1N1. Principles of infection control should be reinforced at clinic visits (see ‘Infection Control Recommendations for Novel Influenza A/H1N1’ section).
  • • 
    Transplant patients and candidates should be vaccinated with at least one dose of H1N1 vaccine. Whether more than one dose is required to achieve immunogenicity will depend on the type of vaccine. In healthy adults, a single dose of inactivated split-virus 2009 H1N1 vaccine had a seroconversion rate of 96.7% (18). Another H1N1 vaccine containing the adjuvant MF59 had a seroconversion rate of 76% after a single dose (19).
  • • 
    Transplant recipients, candidates and household contacts should also receive the annual trivalent inactivated influenza vaccine in addition to H1N1 vaccine. If a transplant recipient has already received vaccine pretransplant, there is no need to give a repeat dose posttransplant.
  • • 
    The seasonal influenza vaccine is generally recommended to be given starting 3–6 months after transplant (20). Given the rapid spread of H1N1 virus, transplant recipients can begin to receive H1N1 vaccine as soon as one month posttransplant. However, the immune response of early vaccination may only be partially protective.
  • • 
    Although the risk of adverse effects (local and systemic reactions) with H1N1 vaccine is largely unknown, there is no reason to believe that adverse effects will be greater than those seen with the seasonal annual influenza vaccine.
  • • 
    If only adjuvanted H1N1 vaccine is available, this should be given to SOT recipients. Adjuvants act locally to attract greater number of antigen-presenting cells to the site of vaccination and reduce the amount of antigen necessary for an effective vaccine response. There is no evidence that adjuvants increase the risk of allograft rejection.
  • • 
    Pregnant SOT recipients are a priority group for vaccination.
  • • 
    Pneumococcal vaccine should also be updated given the risk of pneumococcal super- infection in those infected with influenza.
  • • 
    Health care workers in contact with SOT candidates and recipients should also be immunized with both seasonal and novel H1N1 vaccines. Both vaccines can be administered simultaneously in opposite arms.

Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References
  • • 
    Intranasal influenza vaccine is a live attenuated virus vaccine and should not be given to SOT recipients.
  • • 
    Persons who receive LAIV may shed virus for up to 21 days postimmunization (21). There may be a theoretical and undefined risk of transmission of vaccine strain virus to transplant recipients from close contacts who receive intranasal influenza vaccine.
  • • 
    For health care workers in contact with transplant recipients, if both inactivated and live vaccines are available, then inactivated vaccine is preferred. However, if only live vaccine is available, those caring for transplant recipients should be vaccinated. All health care workers should be reminded to observe strict hand hygiene which is especially critical for those that have received live vaccine. The use of masks may be considered as well.
  • • 
    For household contacts, if both inactivated and live vaccines are available, then inactivated vaccine is preferred. However, if only live vaccine is available, vaccination should still be given. In this circumstance, the importance of good hand hygiene practices and minimizing contact with secretions (e.g. sharing food/drink, direct saliva contact) should be emphasized to the patient and their household contacts.

Organs from a donor who has received the LAIV can be utilized. Vaccine virus has not been shown to replicate in lung tissue (21).

Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References
  • • 
    Clinical presentation: Influenza illness is more likely to present in a nonspecific manner in young infants compared to older children and adults. Young infants, for example, may present with a sepsis-like picture. In addition, diarrhea may be seen in younger children. When influenza illness is present in young children, the likelihood of illness among adult family members is high. Thus, when a child presents with influenza illness to a health care setting, the accompanying family member might also have influenza illness.
  • • 
    Infection control: Compliance with infection control measures is difficult in young children. The use of masks poses practical challenges in very young infants. In addition, young children are not likely to be compliant with accepted respiratory etiquette. Viral shedding may be more prolonged and copious in young children compared to adults. Thus, the young SOT patient is expected to shed virus for an even more prolonged period, and be more likely than adults to spread the virus to close contacts and to the environment. Family members should use frequent hand hygiene for themselves and their children.
  • • 
    Immunizations:
    • ○ 
      Seasonal influenza vaccine is approved for infants and children greater than 6 months of age. Children under the age of 9 years who are receiving seasonal influenza vaccine for the first time will require two doses, 1 month apart.
    • ○ 
      Pediatric transplant recipients >6 months of age should also receive H1N1 vaccine. All household and close contacts of pediatric SOT recipients should also be vaccinated. Pediatric SOT recipients 6–12 months of age should be a priority group for vaccination, given the paucity of data on the use of antiviral agents in infants <12 months of age. Pediatric transplant recipients do respond to influenza vaccines, although their cellular responses may not be as vigorous as that found in healthy children (22).
  • • 
    Antiviral agents: The approach to the use of antiviral agents in the treatment and prophylaxis of novel H1N1 influenza in children is similar to adults and has been adapted from existing CDC and other guidelines. The recommended dosing is shown in Tables 2 and 3. There are age-related issues that should be highlighted as follows:
Table 2.  Dose recommendations for children 12 months of age or greater
AgeTreatment (duration = 5 days)Chemoprophylaxis (duration = 10 days)
  1. 1Zanamivir use is impractical below 7 years of age.

Oseltamivir
 Children ≤15 kg30 mg twice daily30 mg once daily
 Children 15–23 kg45 mg twice daily45 mg once daily
 Children 24–40 kg60 mg twice daily60 mg once daily
 Children >40 kg75 mg twice daily75 mg once daily
Zanamivir1
 ChildrenTwo 5-mg inhalations (10 mg total) twice daily [age, 7 years or older]Two 5-mg inhalations (10 mg total) once daily [age, 7 years or older]
Table 3.  Dose recommendations for children less than 12 months of age (weight-based dosing preferred; see footnote)
AgeTreatment with oseltamivir (duration = 5 days)Chemoprophylaxis with oseltamivir (duration = 10 days)
  1. Note: Dose adjustments are recommended for patients with creatinine clearance between 10 and 30 mL/min. For these patients, the treatment dose is reduced to a once daily dose. Similarly, the prophylaxis-dosing regimen is altered, with the dose being given every other day.

  2. • Based on preliminary data from a National Institutes of Health-funded Collaborative Antiviral Study Group (CASG) some experts recommend weight-based dosing of oseltamivir for children aged younger than 1 year, particularly for very young or premature infants based on preliminary data.

  3. • Weight-based dosing for infants less than 12 months of age: Treatment

  4.  ○ 9 months to ≤12 months should receive 3.5 mg/kg/dose b.i.d.

  5.  ○ <9 months should receive 3.0 mg/kg/dose b.i.d.

  6. • Weight-based dosing for infants less than 12 months of age: Chemoprophylaxis

  7.  ○ 9 months to ≤12 months: 3.5 mg/kg/dose qd

  8.  ○ <9 months: 3.0 mg/kg/dose qd

  9. Source: D. Kimberlin et al. Oseltamivir (OST) and OST carboxylate (CBX) pharmacokinetics (PK) in infants: Interim results from a multicenter trial. Abstract presented at Infectious Diseases Society of America Meeting, October 2009.

  10. Health care providers should be aware of the lack of data on safety and dosing of oseltamivir in seriously ill young infants with confirmed 2009 H1N1 infection or following exposure to a confirmed 2009 H1N1 influenza case. Infants should be carefully monitored for adverse events when oseltamivir is used. A pediatric infectious disease consult is advised. Additional information on oseltamivir for this age group can be found at: http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM153547.pdf

<3 months12 mg twice dailyNot recommended unless situation judged critical due to limited data on use in this age group
3–5 months20 mg twice daily20 mg once daily
6–11 months25 mg twice daily25 mg once daily
  • (i) 
    There was initial concern regarding the safety of oseltamivir in infants less than 1 year of age. This was based on animal data using drug exposures that were several fold greater than what would be experienced in infants. While data are emerging, the collective body of evidence relating to the safety of oseltamivir in infants less than 1 year of age is increasing. As such, at this point in time, current consensus favors the use of oseltamivir in infants less than 1 year of age.
  • (ii) 
    The dosing of infants less than 1 year of age remains problematic, as data are limited on appropriate dose of oseltamivir in this age group, notably neonates and those with lower body weights. For these infants, most experts now prefer dosing based on body weights where such weights are available. In all situations, an infectious diseases expert must be consulted when antiviral agents are being considered in this age group.

Infection Control Recommendations for Novel Influenza A/H1N1

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References
  • • 
    Influenza is transmitted through large respiratory droplets produced during coughing or sneezing, which can be directly deposited on the mucosal surfaces of people who are within 3 to 6 ft. of the infected patient.
  • • 
    Aerosolized respiratory secretions may also contaminate nearby surfaces leading to spread when susceptible individuals touch contaminated areas and then touch mucosal surfaces on their face.
  • • 
    Influenza A remains viable on hard nonporous surfaces like countertops for 24–48 h, while it may persist less than 8–12 h on porous materials such as cloth or paper. Viruses can survive much longer on wet surfaces, though dry virus particles may live for 3 h on human hands (23).
  • • 
    SOT candidates and recipients who present at health care facilities including physician offices should be encouraged by signs and personal inquiry to identify themselves immediately if they have symptoms of influenza-like illness. Cough etiquette should be encouraged, and tissues and hand sanitizer should be provided. Masks should be provided to patients who are actively coughing and sneezing until they can be placed in a private room.
  • • 
    A system for separating possible influenza cases from other patients is strongly recommended but sometimes cannot distinguish one respiratory viral infection from another.
  • • 
    If an SOT recipient requires admission to the hospital for influenza-like illness, isolation using Standard and Droplet Precautions should be implemented. This requires that health care personnel wear a surgical or procedure mask, nonsterile gloves and nonsterile gowns (24).
  • • 
    Patients should be placed in private rooms with the doors kept closed. If private rooms are not available, H1N1 influenza patients may be cohorted once the diagnosis has been confirmed. Consideration should be given to rooming patients in wards away from the ‘traditional transplant ward’.
  • • 
    Isolation precautions should continue until hospital discharge, or until the signs and symptoms of influenza have resolved and the patient has been afebrile for at least 24 h. Due to the possibility of prolonged viral shedding and atypical symptoms, it is reasonable to maintain Droplet Precautions until hospital discharge if possible, or documentation of a negative test for H1N1 (25).
  • • 
    Hospital visitors with respiratory symptoms should be discouraged. Healthy visitors should be required to wear appropriate personal protective equipment when visiting infected patients, including a surgical mask and gloves (26). Household contacts of the influenza patient, who may themselves be experiencing early symptoms of influenza, should be screened closely for symptoms and encouraged to stay home if appropriate. Unimmunized household contacts may be candidates for antiviral prophylaxis.
  • • 
    Patients with influenza are contagious to others 1 day before symptoms develop. Adults remain infectious for approximately 5 days after symptom onset, although immunosuppressed individuals and children may be contagious for 10 or more days.

Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References

Prevention of donor-derived influenza

  • • 
    During an influenza pandemic, all donors and recipients should be screened for clinical symptoms and signs of recent flu-like symptoms. Every potential organ donor and recipient must be evaluated individually, with specific guidance if needed from infectious disease specialists or clinical microbiologists. Even with other causes of death, potential for influenza illness and/or carriage should be considered. Nosocomial transmission has occurred, thus a prolonged hospital stay does not preclude novel H1N1 infection. In general, centers should have a low threshold to test potential donors and recipients.
  • • 
    Many of the rapid tests are poorly sensitive (11) and thus more sensitive testing should be used, optimally with a sensitivity of over 90%. The relatively short duration of positive assays (often 5–7 days or less from the onset of symptoms) should be taken into consideration when screening donors and recipients with recent flu-like symptoms.
  • • 
    Potential organ donors who have been diagnosed as recently having influenza (e.g. within the previous 2 weeks) should likely be deferred from lung and small bowel donation; those donors with influenza who have received appropriate antiviral therapy could be considered as potential non-lung or small bowel organ donors, after obtaining input from the organ procurement organization's medical director and local infectious disease experts (see also UNOS website; http://www.unos.org/news/newsDetail.asp?id=1292).
  • • 
    There are currently no data on the duration of therapy required for the donor before organs can be safely used. Accordingly, until more data are available many would recommend a 5- to 10-day course of therapy (at therapeutic, not prophylaxis doses) for the recipient if the donor did not complete a course of treatment.
  • • 
    Since only a very small number of cases of peritransplant novel H1N1 infection have occurred, organ procurement in the presence of suspected infection should be carefully evaluated. If the potential living donor is found to have novel H1N1 then transplantation should be deferred if possible until the donor has received a course of treatment and is clinically well.

Identification of donor-derived influenza

  • • 
    When transmission of influenza is suspected, attempts should be made to fully diagnose disease in both the donor (when possible) and recipient. Transplant centers may wish to bank blood specimens and nasal washes or nasopharyngeal swab samples for further diagnostics. When influenza is diagnosed and felt to be donor-derived in origin, other centers with recipients from the same donor should be notified through local organ procurement organization.

Management of donor-derived influenza

  • • 
    Donor-derived influenza in SOT recipients should be treated with oseltamivir and/or zanamivir, depending on the individual patient and local resistance patterns at the time of transplant, similar to the recommendations by the WHO, CDC and others (see ‘Treatment of Novel Influenza A/H1N1’ section). With emerging resistance, optimal treatment recommendations may evolve over time.
  • • 
    Since recent SOT recipients are often in their deepest period of immunosuppression, clinicians caring for such patients may elect to increase the duration of treatment and continue antiviral therapy until viral replication has been documented to be eradicated.
  • • 
    Recipients should be monitored closely for allograft rejection, and for coinfection or superinfection with Streptococcus pneumoniae, Staphylococcus aureus, cytomegalovirus, Pneumocystis jiroveci pneumonia or other infections. In addition, clinicians should consider minimizing immunosuppression if possible, although the risk of rejection in the early transplant period must be weighed against the risk of influenza on an individual basis.

Conflict of Interest Statement

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References

D.K., Research support (clinical trial)—Adamas; S.A.F., M.I.M.—none; E.A.B., Research support (clinical trial)—Roche and Viropharma; Consultant—Roche; A.H., Research support—Roche; M.G.I., Research support—Roche (Oseltamivir), Adamas (TCAD), BioCryst (peramivir); M.G.M., Research support—Roche (Oseltamivir); M.G., Research support (clinical trial)—Wyeth; Consultant—Roche, Bristol-Myers Squibb; C.N.K., Research support—Wyeth; U.A., Research support—Roche; Advisory Board, Roche.

References

  1. Top of page
  2. Abstract
  3. Background and Significance
  4. Diagnosis of Novel Influenza A/H1N1
  5. Treatment of Novel Influenza A/H1N1
  6. Routine Chemoprophylaxis and Postexposure Prophylaxis
  7. Prevention of Novel Influenza A/H1N1 in SOT Candidates, Recipients and Contacts: Practical Strategies and Immunization Recommendations
  8. Specific Considerations for Live Attenuated Influenza Vaccine (LAIV)
  9. Special Issues of Novel Influenza A/H1N1 for Pediatric SOT Recipients
  10. Infection Control Recommendations for Novel Influenza A/H1N1
  11. Donor-Derived Novel Influenza A/H1N1: Prevention, Identification and Management
  12. Conflict of Interest Statement
  13. References