Should Health-Care Providers in the United States Have Access to Influenza Vaccines Formulated for the Southern Hemisphere?

Authors

  • Raymond A. Strikas MD,

    Corresponding author
    1. National Vaccine Program Office, Department of Health and Human Services, Washington, DC, USA
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  • Phyllis E. Kozarsky MD,

    1. Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA
    2. Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA, USA
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  • Christie Reed MD,

    1. Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA, USA
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  • Brian K. Kapella MD,

    1. Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA, USA
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  • David O. Freedman MD

    1. Center for Geographic Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA
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  • This article was presented in part at the ISTM conference, May 23, 2007, in Vancouver, British Columbia, Canada.

Raymond A. Strikas, MD, National Vaccine Program Office, Department of Health and Human Services, 200 Independence Avenue, S.W., Room 443H, Washington, DC 20201, USA. E-mail: raymond.strikas@psc.hhs.gov

Abstract

Background Influenza is the most common vaccine-preventable disease in travelers. It circulates year-round in the tropics, November to March in the northern hemisphere (NH), and April to October in the southern hemisphere (SH). In 2005, approximately 8.5 million US adults aged 18 years and older traveled to the Caribbean. A similar number traveled to the tropics and the SH. SH formulation of influenza vaccine is not available in the United States. We surveyed International Society of Travel Medicine (ISTM) members to ask if they would use SH influenza vaccine if available.

Methods We electronically mailed a survey in December 2006 to 1,251 ISTM members in the United States. We asked if respondents would use SH vaccine for patients traveling to the SH or tropics, how many such patients per week they see, and their practice location.

Results We received 157 responses for a response rate of 12.5%. Of these, 129 (82%) stated that they would be interested in having SH influenza vaccine available. Of those indicating interest, 73 (60%) reported seeing >10 patients traveling to the SH or tropics each week. Respondents reported practice settings in 34 states and the District of Columbia. Respondents requested more information about the likely cost of SH influenza vaccine, ordering conditions, vaccine use guidelines, comparability with NH vaccine, and approval of SH vaccine by the Food and Drug Administration.

Conclusions Many travelers to the SH are at risk for influenza infection. Although only a limited number of ISTM members responded, respondents indicated considerable interest in availability of SH influenza vaccine for their patients. More data from travel medicine and other practitioners are needed on this topic. Inquiries are being made of influenza vaccine manufacturers about licensing SH influenza vaccines in the United States. Adding SH influenza vaccine to the vaccines available to NH clinicians could help mitigate the morbidity of influenza in travelers.

Influenza is the most common vaccine-preventable disease in travelers. Influenza-confirmed illness incidence has been estimated at 1/100 person-months traveling to all parts of the world.1 Cruise ship outbreaks in both the southern hemisphere (SH) and the northern hemisphere (NH) have documented 17% to 37% influenza-like illness attack rates.2,3 These ships often host an admixture of passengers and crew from both hemispheres simultaneously. Influenza viruses circulate year-round in the tropics, November to March in the NH, and April to October in the SH4 (Figure 1). In 2005, approximately 8.5 million US adults aged 18 years and older traveled to the Caribbean, with almost an equal number traveling to the tropics and SH [Centers for Disease Control and Prevention (CDC), unpublished data; Table 1]. The CDC’s Advisory Committee on Immunization Practices recommends that any traveler who wishes to reduce the risk for influenza infection should consider influenza vaccination.5 This recommendation is challenging because the NH influenza vaccine usually only becomes available in September each year and expires the following year on June 30. It is often not available for some months before the expiration date. Since 1999, influenza vaccines have been produced in two formulations, one each for the NH and SH in sequential 6-month cycles, to allow for the best possible match between wild viruses and vaccine strains.6 One or two of the vaccine strains have been different in 5 of the 9 years since 19997 (Table 2). One strain difference was noted in 4 of the 5 years with differences and two in the other, resulting in 6 years with differences. In those years with strain differences between the two vaccine formulations, significant antigenic similarity of NH vaccine strains for circulating SH viruses occurred for only one of the six strains (CDC, unpublished data). Therefore, given better representation of circulating SH influenza viruses in most years’ SH vaccine and unavailability of year-round NH vaccine, persons traveling to the SH should ideally receive SH influenza vaccine for optimal protection. The SH formulation of influenza vaccine, while sold in many countries (Table 3), is neither presently approved for use or distributed in the United States nor commonly available in other NH countries. Data are needed on the level of interest in SH vaccine by health-care providers, particularly specialists who advise travelers, should it become available in the United States.

Figure 1.

Seasonal occurrence of influenza. Adapted from Viboud C and colleagues 2006, figure 1, comparison of influenza seasonal patterns in temperate and tropical countries in the Americas (from lat +39° N to −35° S).

Table 1.  2005 estimates of US travelers aged 18 years and older to tropics and the southern hemisphere
DestinationNo. of travelers (million)
  1. Source: Centers for Disease Control and Prevention, unpublished data, and 2005 HealthStyles Survey.

Central and South America3.3
Australia, New Zealand1.3
Oceania1.2
Asia (minus Japan)2.6
Subtotal8.4
Caribbean8.5
Total16.9
Table 2.  Differences between northern and southern hemisphere influenza vaccines, 1999 to 2006*
YearNorthern hemisphereSouthern hemisphere
1999–2000A/Sydney/5/97 (H3N2)A/Moscow/10/99 (H3N2)
A/Beijing/262/95 (H1N1)A/New Caledonia/20/99 (H1N1)
2000–2001B/Beijing/184/93B/Sichuan/379/99
2003–2004A/Moscow/10/99 (H3N2)A/Fujian/411/2002 (H3N2)
2004–2005A/Fujian/411/2002 (H3N2)A/Wellington/1/2004 (H3N2)
2005–2006B/Shanghai/361/2002B/Malaysia/2506/2004
Table 3.  Countries where southern hemisphere influenza vaccine is available
  1. Source: Personal communications from CSL, GlaxoSmithKline, Sanofi Pasteur, and Solvay.

Argentina
Australia
Bolivia
Brazil
Chile
Costa Rica
Curacao
Ecuador
Hong Kong
Indonesia
Kenya
Madagascar
Malaysia
Mauritius
New Zealand
Panama
Paraguay
Peru
Philippines
Singapore
South Africa
Thailand
Uruguay

Methods

We surveyed United States–based members of the International Society of Travel Medicine (ISTM) to ask if they would use SH influenza vaccine if it were available.

We sent a three-question survey once electronically to 1,251 ISTM members listed for 2005 and/or 2006 and requested return within 3 weeks. The questions, with response categories of yes, no, maybe, were as follows:

  • 1If a southern hemisphere influenza vaccine were available in the United States, would you be interested in making it available to your patients?
  • 2How many travelers do you see (weekly) between March and September who are traveling to the tropics or the southern hemisphere?
  • 3Please list the state in the United States where your practice is located.

Comments could be added to any of the questions. Frequencies of responses and percent answering each response were calculated. The number of respondents adding comments was also calculated for each type of comment.

Results

We received 157 unique responses of 1,251 solicited in the United States for a 12.5% response rate. Respondents reported practice settings in 34 states and the District of Columbia. Respondents from Belgium (one) and Japan (one) were excluded. The most common practice locations were California [21 of 168 (12.5%)], New York [14 of 104 (13.5%)], Texas [12 of 77 (15.6%)], Massachusetts [10 of 50 (20%)], and the District of Columbia [10 of 18 (55.6%)]. When we compared the rate of response from the different practice locations, District of Columbia health-care providers were more likely to respond than those from the first four locations (p < 0.001).

A total of 129 respondents (82%) reported that they would be interested in having SH vaccine available for their patients. An additional 25 (16%) reported that they may have an interest, 2 (1%) reported no interest, and 1 (0.6%) reported that they do not offer any vaccines in their practice.

Of those who indicated interest in this vaccine and who reported the number of travelers seen in their practice per week, 73 (60%) reported seeing >10 patients traveling to the SH or tropics each week and 49 (40%) reported seeing ≤10 such patients per week (Figure 2). Of those with possible interest, 18 (75%) reported seeing >10 such patients per week.

Figure 2.

Frequency of travelers to the southern hemisphere (SH) and tropics per practice per week stratified by practice interest in SH influenza vaccine.

Based on our review of the comments from respondents replying “maybe” as to whether they would use SH vaccine if available, we categorized these comments into four areas. Two scientific concerns were as follows: (1) the SH vaccine’s utility in comparison to NH vaccine should be clearly defined, with clear guidance for use (10 respondents) and (2) risk and benefit for patients should be defined (two respondents). Two practical concerns included (1) vaccine costs, minimum purchase amount, and time to order should be defined (nine respondents) and (2) the vaccine’s approval by the Food and Drug Administration (FDA) (two respondents).

Conclusions

Respondents to our survey demonstrated a clear interest in having SH influenza vaccine available for their patients who travel to the SH. Most of these practitioners see more than 10 patients per week for whom this vaccine could be recommended. The concerns evinced by the respondents could be readily addressed, given the vaccine would require approval by the USFDA. Inquiries are being made of influenza vaccine manufacturers about the feasibility of licensing SH influenza vaccines in the United States. Production and licensure of SH influenza vaccine in the United States should be fairly straightforward for companies already having licensed other influenza vaccines, given identical production processes and clear licensure guidelines.8 Thereafter, recommendations for its use would be published by the CDC’s Advisory Committee on Immunization Practices, likely in its annual influenza vaccine recommendations.5 These recommendations address risk and benefit of annual vaccination with the NH vaccine and would do so also for any FDA-approved SH vaccine. The recommendations would also need to distinguish between recommended uses of the SH and NH vaccines. The World Health Organization already recommends that travelers to the SH or tropics receive SH vaccine if feasible.9 Cost of this vaccine and ordering requirements would be addressed by vaccine manufacturers and distributors, if and when such a vaccine were approved. Both vaccines would probably be available at the same time during most of the period beginning in the late winter through the fall each year. To avoid confusion between the two, manufacturers and public health and travelers’ health authorities would need to employ creative labeling and information efforts for health-care providers. Practitioners who elected to offer both SH and NH vaccines would have to be careful in their ordering and vaccine-handling practices to avoid confusing the two vaccines and to have both available at the appropriate times of the year. Recommendations for the respective vaccines’ use in the same country should address the appropriate time interval between receipt of each vaccine because a traveler could receive the SH vaccine in August and then request the NH vaccine as early as September. Existing data do not suggest any contraindication to administering one influenza vaccine a month or more after a different influenza vaccine was received.10–12 In addition to travelers to the SH and tropics, the Defense Health Board (DHB) of the US Department of Defense has evinced interest in SH influenza vaccine for active duty personnel.13 The DHB encouraged better influenza surveillance by the military in developing areas such as Africa and simultaneously encouraged manufacturers to seek licensure of SH vaccines in the United States (Dr. Gregory Poland, Chair of the DHB, personal communication, October 8, 2007).

Our survey was limited by the low response rate, and therefore, it would be helpful to collect more data from travel medicine practitioners on this topic. We limited the response time to 3 weeks, did not issue any reminders to complete the survey, and did not use standard mail or an Internet site to garner additional responses. However, we note that over 50% of US air travel to the Caribbean, tropics, and SH originates from the five most commonly reported practice areas in our survey, suggesting significant interest among practitioners in these areas about SH influenza vaccine.14 While the survey was only for practitioners who reported to ISTM that they were based in the United States, it would be important before implementation of SH vaccine to assess the interest of travel medicine practitioners in other NH countries. Also, because travelers to areas such as the Caribbean may not see travel medicine practitioners, others, such as internists, family medicine physicians, and community vaccination providers, should also be surveyed to assess their attitudes toward possible use of SH influenza vaccine. Adding SH influenza vaccine to the armamentarium of vaccines available to NH clinicians could help mitigate the morbidity of influenza in travelers. In addition, making NH influenza vaccine available to SH health-care providers should also be considered. Influenza affects travelers from the SH to the NH, and there are recommendations in Australia for travelers to consider receiving NH vaccine when traveling to the NH between October and March.2

Acknowledgments

We thank Ann Moen and Alexander Klimov, both from CDC, for their assistance in providing influenza surveillance data. The survey described was sponsored by the ISTM and Geosentinel. The survey was not a clinical trial and therefore was not registered in a public trials registry.

Declaration of interests

D. O. F. has accepted honoraria and consulting fees from Novartis Vaccines. The other authors state that they have no conflicts of interest.

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