Peer Reviewed

travel history

A College Senior Seeks Advice Regarding a Semester of Travel

Ronald Rubin, MD—Series Editor

A college senior visits the office to seek knowledge and advice regarding on an upcoming summer of volunteer work in Africa. He will be helping children to learn English mainly in Kenya, but likely will try to travel as conditions permit in neighboring countries as well. His main schools will be located in the ex-urban countryside areas outside the capital, Nairobi. He wants to know what preparations he should make regarding vaccinations, prophylaxis medicines and related traveler’s infectious disease issues.


He is an otherwise healthy 22-year-old young man who is up-to-date in regards to all recommended vaccinations throughout his lifetime, including revaccination and boosters prior to starting college. 

Physical Examination

As expected, his physical exam is totally within normal limits.

Which of the following is the most indicated travel prophylaxis he requires in relation to his plans?

A. Dengue fever vaccination.

B. Yellow fever vaccination.

C. West Nile virus vaccination.

D. Three-week course of doxycycline coincident with his arrival to prevent rickettsial diseases, such as typhus.

Answer and discussion on next page

Correct Answer: B

Essentially all of the answers offered for this question deal with reasonable concerns for someone traveling to an endemic, frequently underdeveloped tropical region of the world. However, for a variety of reasons, Answer B, yellow fever vaccination, is the most useful and appropriate of the choices given.


Yellow fever virus is the most virulent of the flaviviruses, which also include West Nile virus and dengue. Clinical illness caused by yellow fever virus is severe and carries a very significant mortality risk with it. 

Typical illness begins 3 to 6 days after infection, otherwise known as the incubation period. The acute, viremic phase manifests fever, severe myalgias and headaches, chills, and nausea/vomiting.Physical and laboratory findings include bradycardia despite fever, neutropenia, and elevated transaminases. Most patients recover from this viremic phase within a week, but in 15% to 25% of those infected, a toxic second phase ensues shortly thereafter and includes the return of hectic fevers, acute fulminant hepatitis, significant bleeding dyscrasia with skin (petechiae, ecchymosis), and more morbidly, gastrointestinal hemorrhage including melena, hematemesis, and hematochezia. Eventually, hypotension and shock will ensue—approximately 50% (or 7.5%-12.5% of all initially infected patients) of patients dying within 10 to 14 days.1 

Of interest is the pathophysiology involved which seems more cytokine dysregulation—similar to the hemophagocytic dysregulation syndrome rather than viremia or direct hepatic infection of hepatocytes—but this will be a topic for another column.

Those who recover, recover fully—without chronic organ damage or sequelae. Therapy is supportive as no antiviral or immune therapies have been shown to be effective. Infection does seem to confer subsequent lifelong immunity against reinfection with yellow fever virus.


The strikingly high mortality rate far exceeds that of the other infections listed above. The index student is going to East Africa, where yellow fever is endemic and periodic outbreaks are routine.1 

A very effective vaccine that develops antibodies against 2 substrains, 17D-204Y and 17DD, is available. One dose results in protective antibody response within 10 days in 95% of vaccinated persons. A booster is given after 10 years with this regimen resulting in lifelong immunity.3 The vaccine is quite safe with rare, host-dependant neurotropic (encephalitis) or viscerotropic (hepatic failure) syndromes encountered in 0.2 to 1 per 100,000 people under age 60 and 3 per 100,000 people over age 60.

Our student, besides going to a high-risk region, is young and otherwise healthy so indeed should receive the vaccine.

Differential Diagnosis

Dengue fever (Answer A) is a serious traveler’s febrile illness also caused by a flavirivirus. However, no vaccine is yet available for use at this time5 so this answer is not possible and thus, incorrect. Similarly, there is currently no West Nile Virus (WNV) vaccine (Answer C) available for humans at this time. A commercially available WNV horse vaccine is on the market, but its efficacy in horses, let alone its human efficacy, safety, and toxicity, are unknown.

A formaldehyde-inactivated vaccine does exist for typhus (Rickettsia prowazekii). Two doses 4 weeks apart are required, followed by boosters every 6 to 12 month. However, vaccination against typhus is not required as a condition for entry in any country. Further production of typhus vaccine has been discontinued in the United States. A single 200 mg dose of doxycycline is effective therapy for typhus. An extended course as listed in Answer D is not required.

Outcome of the case on the next page

Outcome of this Case 

Yellow fever vaccination was advised and administered. He had a productive, enjoyable, and uneventful (from an infectious disease point of view) 3 month stay in East Africa. He had one minor bout of “travelers’ diarrhea” that resolved with symptomatic therapy. n

Ronald Rubin, MD, is a professor of medicine at Temple University School of Medicine and chief of clinical hematology in the department of medicine at Temple University Hospital, both in Philadelphia.


1. Markoff L. Yellow fever outbreak in Sudan. N Eng J Med. 2013;368:689-691.

2. Sung L, Weitzman S, Petric M, King SM. The role of infections in primary hemophagocytic lymphohistiocytosis: a case series and review of the literature. Clin Infect Dis. 2011;33:1644-1648.

3. Monath TP. Review of the risks and benefits of yellow fever vaccination including some new analyses. Expert Rev Vaccines. 2012;11:427-48.

4. Centers for Disease Control and Prevention. Adverse events associated with 17D-derived yellow fever vaccination. United States 2001-2002. MMWR. 2002;51:989-993.

5. Simmons CP, Farrar JJ, Vinh Chan NV, Wills B. Dengue. N Eng J Med. 2012;366:1423-1443.