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 NIAID's
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. Vinetz' 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, it's most likely that the patient
had been infected for more than 40 years, and possibly for nearly her
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. Vinetz' 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 NIAID's Laboratory of Parasitic Diseases. Dr. Vinetz also received
support from a Physician Postdoctoral Fellow Award from the Howard
Hughes Medical Institute.
NIAID, part of the National Institutes of Health (NIH), supports
biomedical research to prevent, diagnose and treat illnesses such as
AIDS, tuberculosis, malaria, asthma and allergies. NIH is an agency
of the U.S. Department of Health and Human Services.
Press releases, fact sheets and other NIAID-related materials are
available via the NIAID home page at http://www.niaid.nih.gov.