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July 2005 A patient presenting with flu-like symptoms during the dog days of summer should be evaluated for tick-borne disease, according to W. Michael Scheld, MD, who spoke recently at the Clinical Infectious Disease Meeting in Orlando, Fla. Scheld is the Bayer-Gerald L. Mandells Professor of Internal Medicine, clinical professor of neurosurgery, University of Virginia Health Sciences Center, Charlottesville.
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The presentation of tick-borne disease is nonspecific. Patients often have symptoms similar to influenza (fever, headache and myalgia), excluding cough. “When this occurs in the summer time, you should be considering tickborne disease,” Scheld said.
The diagnosis is clinical and therefore treatment should be started prior to diagnostic testing. “This is changing because polymerase chain reaction (PCR) is becoming available for the diagnosis of many of these diseases and can be done rapidly,” he said.
Patients with tick-borne disease may or may not present with a characteristic rash or symptoms. Scheld reminded the audience that tick-borne illness is seasonal and the geographic distribution is suggestive. Abnormalities may be present in the complete blood count (CBC) and elevations in transaminase are frequent, he noted.
Doxycycline is the gold standard of treatment for most common tickborne illnesses such as Lyme disease, Rocky Mountain spotted fever (RMSF) and ehrlichiosis.
“This is true, even in children,” Scheld said. “The prognosis in children is generally good. Most serious complications occur in adults, especially the elderly.”
There is a convergence of disease in tick vectors, therefore, Scheld suggested, the co-infection rate is likely underestimated. The tick that transmits Lyme disease, Ixodes scapularis, also transmits the agents of HGE and babesiosis. The tick that transmits RMSF also transmits human monocytic ehrlichiosis (HME), and there are other overlaps, according to Scheld.
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Tick-borne encephalitis (TBE) is “absolutely exploding in Europe,” Scheld said. “It is their West Nile.”
In eastern Europe, Scandinavia and warmer regions of the Soviet Union, the disease incidence is increasing dramatically. According to Scheld, the disease is appearing in areas previously unaffected by ticks, possibly because of global warming.
Scheld mentioned a study from Lithuania of 250 patients with central nervous system (CNS) infection. More than half (133) had TBE, and about 13% had the most severe form of encephalitis. Approximately 4% had paralysis and 5% developed cranial nerve palsy. Permanent CNS dysfunction at about one year post-infection was found in nearly one-third of those patients.
“TBE in Europe is increasing dramatically,” he said. “One example is the Czech Republic. It’s a small country, but they have about 6,000 cases of TBE every year.”
The tick-borne encephalitis found in the United States is known as Powassan encephalitis. It’s a tickborne flavavirus, and is seen mostly in northern New England and southern Canada. Between 1958 and 1998, there were 27 reported cases in Canada and the northeastern United States. However, the incidence appears to be on the rise, according to Scheld. Between 1999 and 2001, four cases were reported in Maine and Vermont. All the patients were originally thought to have West Nile virus, but laboratory tests revealed Powassan encephalitis. There were no fatal cases, but all patients had severe neurologic sequelae.
The diagnosis for Powassan encephalitis is made through virus-specific IgM neutralizing antibodies. The virus can be found in four tick species, but is especially prevalent in Ixodes cookei. Reservoirs for infection include squirrels, woodchucks and skunks.
The Lone Star tick is thought to be responsible for several tick-borne diseases, including Borrelia lonestari and HME. The newest pathogen linked to the Lone Star tick is American boutonneuse fever. In August 2004, a 40-year-old man in Virginia presented with fever, headache, myalgias, faint salmon-colored rash and multiple eschars on his legs, according to Scheld. Serology and immunohistochemistry revealed a spotted fever group Rickettsia infection, but the organism grown in culture was identified as Rickettsia parkeri. This was the first R parkeri infection reported in an area outside the Gulf Coast. According to Scheld, as many as five more cases have been reported.
HME is caused by Ehrlichiosis chaffeensis and is spread by the Lone Star tick. The disease has been reported in the southeast, south central and mid-Atlantic regions of the United States. There is an 80% to 90% report of tick exposure, and of those 67% are male. According to Scheld, about 1,500 cases have been reported. The diagnosis of acute disease is by PCR.
“The mortality is low, but it’s not insignificant at nearly 3%,” he said.
Human granulocytic ehrlichiosis is transmitted by deer ticks, as is Lyme disease. Therefore, it’s also found in the Lyme disease endemic regions. Most have tick exposure and more than half of cases are male, according to Scheld.
“This is more common than HME overall. The mortality is low, less than 1%,” he said.
The diagnosis is basically the same as for HME, but morulae are found more often — in more than 20% of cases. “This form of ehrlichiosis is more often associated with rash,” said Scheld.
Ehrlichia ewingii is the third form of ehrlichiosis found in the United States and is also spread by Lone Star ticks and found in the same regions as HME. Diagnosis of E ewingii is the same as HME. Most patients report tick exposure and all reported cases have been male. According to Scheld, most patients with E ewingii have been immunocompromised. “Despite that fact, none of the reported cases have died,” he said.
These diseases are basically a spring and summer illness. Patients have fever, headache, myalgia, malaise and arthralgias.
“They may or may not have a rash and may or may not have a history of a tick bite,” he said.
The cases are sometimes serious and have multiple system organ failure complications.
If a patient presents during the summer with a non-specific febrile illness and has leukopenia or thrombocytopenia with an elevation in transaminases, Scheld suggested testing for ehrilichiosis. “These are found in about 75% to 80% of cases,” Scheld said.
Diagnosis is by PCR and morelli’s or serologic tests. Doxycycline is the treatment of choice or potentially rifampin, according to Scheld.
One of the most recent RMSF studies indicated more than 2,300 cases were reported to the CDC between 1993 and 1996. Of those, 73% were confirmed serologically at the CDC. Cases were reported from 42 states and Washington. While the incidence is highest in children, the overall rate is rising from its current 2.2 per 1 million population. More than 50% of cases occur in the south Atlantic region.
Early studies of RMSF indicated a mortality rate of nearly 5%, but more recent data reveal a lower rate of 1.1%, according to Scheld.
Risk factors for fatal RMSF include age older than 60 years, use of chloramphenicol or any other drug other than tetracycline and treatment after five days of illness. Scheld noted that blacks tend to have worse outcomes with RMSF, possibly because the initial rash goes unnoticed.
Babesia microti is the main pathogen in the United States, which causes babesiosis. About 300 cases a year are reported mainly on Nantucket, Martha’s Vineyard, the eastern end of Long Island and along the Eastern Seaboard. The symptoms range from a mild flu-like illness to fatal infection. It is maintained in nature by the white-footed mouse and the I scapularis tick, similar to Lyme disease. Severe disease is most often found in those over age 55 as well as asplenic patients, those with HIV, transplant patients or patients receiving chemotherapy.
“Transmission is by tick bite, but unlike some of the other diseases, it’s also been transmitted by blood transfusion and by the transplacental route,” Scheld said.
Babesia divergens has been reported in this country since 1957. More than 30 cases have been reported in Europe, and more than 50% have been reported since 1985. It is mostly reported among farmers, foresters, campers and hikers and there is an increased risk with splenectomy, severe hemolysis, hemoglobinuria, jaundice and even death.
Severe babesisosis affects mainly those older than age 60. The risk factors for severe disease, according to a study published in Clinical Infectious Diseases in 2001, include age older than 60 years, splenectomy, immunosuppression, anemia with hemoglobin <10, thrombocytopenia or a high degree of parasitemia.
The diagnosis of babesiosis is by Wright-Giemsa stained thin blood smears. Immunofluorescence antibody test is the diagnostic tool of choice for serology and an ELISA is available for cattle screening. A PCR is promising, according to Scheld.
Quinine sulfate and clindamycin are the standard treatments of choice. Quinine sulfate is given as an oral dose of 650 mg three times daily and clindamycin is given as 1,200 mg orally twice daily for seven days. Blood exchange transfusion is an option for B divergens cases or for extremely severe babesiosis cases, according to Scheld.
Tularemia is a disease confined to the Northern Hemisphere. There are two strains of Francisella tularensis reported in the United States and there are multiple modes of transmission, as well as multiple syndromes, according to Scheld.
Several outbreaks were reported between 1998 and 2000. A large outbreak of tularemia was associated with contaminated water in Kosovo. The disease has also been associated with lawn mowing or brush clearing in Martha’s Vineyard. “Landscapers have had a very big problem with this,” he said.
Rabbits in Spain have also been linked to tularemia outbreaks. In Sweden, cats were responsible for a recent outbreak and mosquitoes have also been to blame, according to Scheld.
Treatment of tularemia is controversial. Patients in the Spain outbreak had success rates of 76.6% with streptomycin. However, ciprofloxacin treated 95% of patients successfully.
“If you read virtually any text book in infectious diseases, including recent editions, they will tell you that streptomycin is the drug of choice for tularemia. My guess is that it’s probably wrong,” Scheld said. “In my judgment, a quinolone is probably the drug of choice for tularemia, as it would be for anthrax as well as plague – so three of the major category A agents probably should be treated with a quinolone.”
By 1996, there were nearly 900 tick species or subspecies recognized. Hard ticks and soft ticks are the two major families of ticks. There are three basic life stages: larva, nymph and adult. Most disease transmission from ticks to humans occurs during the nymph stage. Ticks are second only to mosquitoes as vectors of human disease, Scheld said.
For more information:
- Scheld WM. Tick-borne diseases other than Lyme. Session VI-3. Presented at the Clinical Infectious Disease Meeting. March 31-April 3, 2005. Orlando, Fla.
