A mild case of malaria smoldered in a 74-year-old woman for decades before being correctly diagnosed and successfully treated by a research physician affiliated with the National Institute of Allergy and Infectious Diseases (NIAID), according to a report in this week¹s New England Journal of Medicine.
The unusual case at more than 46 years, and possibly up to 71 years, the longest known malaria infection on record "reveals how high-tech medicine can shed light even on ancient syndromes," says Joseph M. Vinetz, M.D., a postdoctoral fellow in NIAID¹s Laboratory of Parasitic Diseases.
Using an extremely sensitive test that searches for genetic signature sequences of a specific malaria parasite, Dr. Vinetz found evidence of that parasite that had eluded detection in multiple standard smears of blood taken from the patient and examined under a microscope. The genetic test, RT-PCR (reverse transcription-polymerase chain reaction), had recently been developed in the laboratory of an NIAID colleague, Thomas F. McCutchan, Ph.D., primarily for research purposes.
The woman, a native of Greece, came to Dr. Vinetz¹ attention in February 1996 when her daughter, a resident of Baltimore, brought her mother for evaluation to a Johns Hopkins University clinic where Dr. Vinetz works part time. On examination, the woman did not complain of any symptoms but did have an enlarged spleen.
The enlarged spleen, her medical history indicated, was first documented several years earlier during a routine examination in Greece. At that time, she was mistakenly diagnosed with lymphoma and treated with an oral anti-cancer drug, methotrexate, for 10 days.
In response to the chemotherapy, symptoms of malaria appeared but were not recognized as such. After seven days, she developed a recurring high fever and headache every 72 hours, a pattern of fever known since ancient times as specific to malaria. Although these symptoms spontaneously resolved after she discontinued treatment, the enlarged spleen and other signs of an obscure systemic illness remained.
Dr. Vinetz suspected that her persistently enlarged spleen and former bout of recurrent fever could be due to malaria. Although the four types of human malaria infection can all cause an acute illness accompanied by an enlarged spleen, P. malariae is the only one able to cause decades-long asymptomatic infections. People infected with P. malariae usually harbor very low levels of circulating parasites and have normal physical exams.
After using the RT-PCR test to confirm his suspicions, Dr. Vinetz treated the woman with a conventional three-day course of chloroquine. One month after the treatment, Dr. Vinetz could find no traces of the parasite in her blood, and by six months, her spleen had returned to normal size. One year later, she remained free from infection and had gained 22 pounds, making up for years of insidious weight loss attributable to the illness.
Malaria was eradicated in Greece by the early 1950s, and the woman had never traveled outside the country before her journey to Baltimore. An older sister reported that the patient had had malaria at about age 3, and that the disease was untreated but spontaneously resolved. Thus, concludes Dr. Vinetz, it¹s most likely that the patient had been infected for more than 40 years, and possibly for nearly her entire life.
Besides helping solve the mystery of this particular case, the RT-PCR test will be useful for diagnosing very mild cases of malaria in places where the disease has supposedly been eradicated, says Dr. Vinetz. People with low levels of P. malariae parasites, he explains, may have no symptoms but still can be a potential source of transmission to mosquitoes and hence to others. As noted in the paper, "Malaria could be reintroduced into an area where it was once eradicated and where Anopheles mosquitoes are still present. Such a reintroduction of malaria years after documented eradication occurred in the West Indies." That outbreak, reported in 1980, occurred when an individual with asymptomatic P. malariae infection was bitten by a mosquito, which resulted in the infection of dozens and dozens of people.
"RT-PCR is the most sensitive test for picking up any reservoirs of the disease, for trying to determine whether or not vaccine and prevention campaigns have really eradicated malaria," comments Dr. Vinetz.
Dr. Vinetz¹ co-authors on the paper include Jun Li, M.D., Ph.D., Thomas F. McCutchan, Ph.D., and David C. Kaslow, M.D., all of NIAID¹s Laboratory of Parasitic Diseases. Dr. Vinetz also received support from a Physician Postdoctoral Fellow Award from the Howard Hughes Medical Institute.