New-onset headache and fevers in a young volunteer

A public-health student helping to clear debris in New Orleans is exposed to potentially toxic waters.

Mr. C, a 28-year-old public-health student, knew something was wrong when his fevers and rigors continued throughout his wedding ceremony. Five days earlier, while assisting the Hurricane Katrina relief effort in New Orleans, his temperature had risen to 104°F, and he had developed a retro-orbital headache. Over the next few days, the fevers recurred suddenly and periodically, leaving him exhausted when they subsided.

Initial evaluation

One week after symptom onset, Mr. C presented to the emergency department (ED). In addition to the fevers, he complained of neck pain, photophobia, muscle aches, fatigue, and sweats. He had not experienced any weight loss, decrease in appetite, rash, joint swelling or redness, loss of consciousness, numbness or tingling, or weakness. He noted no past medical history. He was not taking any medications, and he had no allergies. Although he reported a history of tobacco and alcohol use, he had quit them both three years ago. He denied any history of IV drug use. Recent tests for HIV and TB were negative. He reported no unusual food intake, no sick contacts, and no travel in the past year.

Mr. C was especially concerned, however, about an incident that occurred shortly before his fevers began. While he was helping to clean up a flooded home, a chandelier fell from the ceiling, sending a spray of water onto his face and into his eyes.

On examination, we noted a thin man with multiple tattoos. He appeared to be in moderate distress and was slightly diaphoretic. Vital signs were temperature 99.5°F, pulse 89 beats per minute, respiratory rate 18 breaths per minute, and BP 108/56 mm Hg. Oxygen saturation on room air was 98%. Laboratory studies found WBCs 5,200/µL (82% neutrophils), hematocrit 39.4%, and platelets 108,000/µL. A chemistry panel revealed aspartate aminotransferase 41 units/L, alanine aminotransferase 26 units/L, total bilirubin 1.8 mg/dL, and alkaline phosphatase 87 units/L. Urinalysis, chest x-ray, head CT, and lumbar puncture were normal. Monospot was unremarkable. Blood cultures showed no growth. The patient was given sumatriptan (Imitrex) for a presumed migraine.

Recurrence prompts re-evaluation

Unfortunately, Mr. C’s fevers continued to recur in two-day cycles. He canceled his honeymoon and came to our clinic. Our initial differential included leptospirosis, borreliosis, rat-bite fever, TB, focal bacterial infection, and endocarditis, as well as underlying malignancy, rheumatologic diseases, and hereditary causes of fever (e.g., familial Mediterranean fever).

The periodic nature of our patient’s fevers prompted a more rigorous investigation into his travel history. Questioning about travel more than one year ago revealed that he had backpacked for a month in Guatemala, including Tikal, an area in the north where malaria is endemic. A few years prior to that, he had served as a Peace Corps volunteer in Kenya, where, despite mefloquine prophylaxis, he had suffered an undefined illness characterized by fever, joint aches, slurred speech, vomiting, and diarrhea. The condition had finally resolved without therapy after two months.

The combination of Mr. C’s travel history, symptoms (headache and fever), and lab findings (slight anemia, thrombocytopenia, and elevated bilirubin) sent us in a new direction. We obtained thick and thin blood smears, and 12 hours later, pathology confirmed the presence of Plasmodium vivax and a diagnosis of malaria. The release of the parasites into the bloodstream causes periodic fevers, as experienced by our patient.

Discussion

This case was illuminating in many respects. First, it illustrated the need to watch out for the red herring. The fact that our patient had become ill shortly after exposure to possibly toxic waters and infection risks suggested a relationship between the two events. This assumption could have prevented further investigation into other risk factors. Second, the diagnosis underscored the need for attention to symptom specifics.

The periodicity of Mr. C’s fevers was a clue because while the differential diagnosis for fever is extensive, the possibilities associated with periodic fevers are much fewer. The fever curve was very important in distinguishing one Plasmodium species from another. Fevers associated with Plasmodium falciparum occur at variable intervals, while the fevers of Plasmodium malariae occur every three days. The classic presentation of P. vivax is termed “tertian fever” and characterized by discrete temperature spikes every 48 hours.

Finally, this case demonstrated the necessity of obtaining a complete history. Although Mr. C had at first described no past medical history or recent travel, further interviewing uncovered a mysterious two-month history of undiagnosed fevers and extensive travel in the more distant past.

Malaria is one of the most common causes of fever in the returned traveler but might not be considered if the travel history is distant. While our patient used mefloquine prophylaxis in Kenya, he took no similar measures while in Guatemala.

Most antimalarial agents act on the parasite while it is in the blood and offer no activity as it resides in the liver. Both Plasmodium ovale and P. vivax are known to reside in the liver and can present more than two months after a traveler returns home. Most latent attacks occur within three years. Current recommendations for individuals who have resided for a prolonged period in areas where P. vivax or P. ovale is endemic or for those known to have been infected with these organisms include the addition of two weeks of terminal prophylaxis with primaquine.

Therapy

Our patient was informed of his diagnosis and tested for glucose-6-phosphate dehydrogenase (G6PD), as primaquine can cause hemolysis in people with G6PD deficiency. Normal test results allowed us to prescribe chloroquine followed by primaquine. Mr. C returned to New Orleans to resume his studies and begin, without fevers and rigors, his married life.

Dr. Said is an internal medicine resident at Johns Hopkins Bayview Hospital, Baltimore, where Ms. Smith is the Web/instructional librarian, and Dr. Wright is an Arnold P. Gold Foundation Associate Professor of Medicine. The authors are indebted to Robin McKenzie, MD, assistant professor of medicine at Johns Hopkins University School of Medicine, in Baltimore, and Michael Eberlein, MD, chief resident in internal medicine at Johns Hopkins Bayview Medical Center, for their assistance.

Read on

  • Pasvol G. Malaria. In: Cohen J, Powderly WG, eds. Infectious Diseases. 2nd ed. St. Louis, Mo.: Mosby; 2004:1579-1591.
  • n Martín-Rabadá P, Bouza E. Blood and tissue protozoa. In: Cohen J, Powderly WG, eds. Infectious Diseases. 2nd ed. St. Louis, Mo.: Mosby; 2004:2443-2447.
  • Fairhurt RM, Wellems TE. Plasmodium species (malaria). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 6th ed. New York, N.Y.: Elsevier/Churchill Livingstone; 2005:3121-3138.
  • Schwartz E, Parise M, Kozarsky P, Cetron M. Delayed onset of malaria—implications for chemoprophylaxis in travelers. N Engl J Med. 2003;349: 1510-1516.
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