Perspectives: Why Guidelines Differ

CDC Yellow Book 2024


Author(s): David Shlim

Numerous international, national, and professional organizations publish guidelines and recommendations for travelers; CDC’s Yellow Book is but one example. Travel health providers should be aware of these recommendations, even though they might not follow them in every instance. Through awareness, travel health providers can explain to their patients how their recommendations, and their patients’ choices, might be discrepant with what others recommend. It can be unsettling for patients to receive travel medicine advice, vaccines, or an antimalarial drug prescription from a provider, only to find that the advice and prescriptions are contradicted by what other professionals, friends, or destination-country nationals have to say. The skillful travel health provider will be able to help the traveler reconcile seemingly conflicting advice, and travelers will be reassured when providers explain why these differences exist.

How Guidelines are Created

In the United States, the Food and Drug Administration (FDA) approves standards for how to use a vaccine or medication, including dosages, ages for which the product is approved, and booster recommendations. Guidance about when to use a product can come from a separate body (e.g., the Advisory Committee on Immunization Practices [ACIP]). To give ACIP the best possible information on which to base their recommendations, working groups of experts hold meetings to review the literature and new studies.

International bodies (e.g., the World Health Organization [WHO]), national committees of other countries, and medical organizations (e.g., the International Society of Travel Medicine and the Infectious Diseases Society of America), also promote their own guidance. Other professional organizations might create consensus clinical practice guidelines based on published medical literature and expert opinion. Travel medicine–specific paid subscription services employ travel medicine experts to organize and present guidelines for health care providers who see international travelers in their practice but who might lack expertise in the subject. Guidance about vaccinations and malaria prophylaxis developed by these organizations and subscription services can differ from CDC advice. Reasons for this are varied and include differences in product availability, licensure standards, cultural perceptions of risk, and opinions among experts, as well as lack of definitive evidence.

Availability of Products

Travel health providers can only use the products available to them. Availability is determined by the regulatory approval status of the product and, to a lesser extent, the marketing and distribution plan of the manufacturer. Regulatory approval processes vary greatly by country. For example, registering a new vaccine or antimalarial drug in the United States is a costly and rigorous process. If the market in a particular country is insufficient to justify the expense of registration, a commercial company might not seek it.

Licensure Standards

Licensure standards also vary. What might be sufficient for one regulatory authority might not suffice for another. For example, primaquine, an option for malaria prophylaxis in the United States, is not registered or commercially available in Switzerland. Atovaquone-proguanil also was available for malaria prophylaxis in the United States before many other countries. In another example, 4 Japanese encephalitis vaccines are available in the world, but only 1 is licensed in the United States.

Differences in Data Interpretation

Even when the same products are available, recommendations for use might not be the same in all countries. The injectable Ty21a typhoid vaccine and the oral typhoid vaccine are examples. In the United States, a booster of the injectable Ty21a vaccine is recommended after 2 years, but in most European countries, a booster is recommended after 3 years. In the United States, health providers dispense a packet of 4 oral typhoid vaccine capsules, whereas in Europe, 3 doses are considered adequate. The regulatory agencies might have reviewed the same data and drawn different conclusions, or they might have reviewed different data at separate times. Regulatory submissions to various agencies rarely occur at the same time. Therefore, for legitimate reasons, the data available for review by each agency might not be the same.

Perception of Risk

People from varying backgrounds can view the same risk data and come to very different conclusions regarding the costs and benefits of minimizing risk to what they consider to be an acceptable level. For example, recommendations to prevent malaria during travel to India vary widely. Germany does not recommend using malaria prophylaxis for any travel to an Indian destination; standby emergency treatment or self-treatment are the only recommendations for identified risk destinations. Guidelines from the United Kingdom recommend only awareness and mosquito bite prevention for more than half the Indian subcontinent, including large cities and popular tourist destinations in the north and south, but suggest prophylaxis consideration for some travelers or for those visiting higher-risk areas. By contrast, CDC recommends malaria prophylaxis for all travelers to any Indian destination, except for some mountainous areas of northern states.

The Impact of Advice

The real question is not just which recommendations each country should adopt, but the possible impact of that advice. Because we do not usually have detailed data on the exact risk to travelers for different vaccine-preventable diseases at a given destination, immunization guidance and recommendations often are based on serologic studies or on the original studies, most often performed in local people, that led to licensing. For example, as noted above, most European countries recommend a booster for the injectable Ty21a typhoid vaccine after 3 years, whereas the United States recommends a booster at 2 years. This difference is based on the perception of falling antibody levels over time, and a decision about where the line of protection against disease falls. Both standards have been in effect for many years, but no current available evidence would lead someone to conclude that one regimen has had a different impact than the other.

An extensive literature review, conducted by the Canadian Committee to Advise on Travel Medicine and Travel, led the committee to limit the recommendation of typhoid vaccine for travelers to South Asia only. This recommendation has not been adopted by CDC or many other international advisory boards. Despite this, we have little evidence that Canadian travelers are experiencing more typhoid fever than their counterparts from other countries.

Similar conclusions can be drawn for malaria prophylaxis recommendations. If the guidance provided by one group or organization consistently resulted in more cases of malaria than another, the guidance likely would change. In the absence of that data, however, health professionals continue to use their best judgment, without much knowledge of the true impact of their advice.

Can We Harmonize Guidelines?

The complex nature of how health organizations obtain, evaluate, and verify data, combined with fundamental differences in risk perception, makes it likely that multiple, overlapping, and at times conflicting guidelines will continue to exist. However, conflicting guidelines have decreased in the past decade due to the efforts of several organizations. A recent example has been the collaboration among the WHO, US CDC, and the European Centre for Disease Prevention and Control to develop consistency and clarity in defining travel-associated risk for Zika infection so that providers can more clearly relay that information, particularly to those who are pregnant or planning pregnancy. In addition, more rapid and frequent communication via the internet and regularly held international conferences have narrowed the gaps between conflicting advice.

In summary, the role of the travel health provider is to understand the differences in guidelines, interpret this information, and convey tailored and informed advice in an assured and comforting manner to travelers. There are no absolute right or wrong answers for many existing travel health guidelines. Even with all the data available, recommendations often are based on expert opinion, which can vary.

The following authors contributed to the previous version of this chapter: David R. Shlim

Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP). Atlanta: The Centers; 2021. Available from:

Chiodini P, Patel D, Goodyer L, Ranson H. on behalf of the PHE ACMP. Guidelines for malaria prevention in travellers from the UK 2021. London (UK): Public Health England. Available from:

Committee to Advise on Tropical Medicine and Travel (CATMAT). Canadian recommendations for the prevention and treatment of malaria. Ottawa (CA): Public Health Agency of Canada; 2021. Available from:

German Society for Tropical Medicine and International Health Association (DTG). [Recommendations for the prophylaxis and treatment of malaria of DTG 2018]; 2018. Available from:

Hill DR, Ericsson CD, Pearson RD, Keystone JS, Freedman DO, Kozarsky PE, et al. The practice of travel medicine: guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(12):1499–539.

Mace KE, Lucchi NW, Tan KR. Malaria surveillance—United States, 2017. MMWR Surveill Summ. 2021;70(2);1–35.

World Health Organization. International health regulations (2005). Geneva: The Organization; 2005. Available from:

World Health Organization. International travel and health. Geneva: The Organization; 2012. Available from:


. . . perspectives chapters supplement the clinical guidance in this book with additional content, context, and expert opinion. The views expressed do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).