LymeNet Newsletter Volume 3 Issue 18

Volume: 3
Issue: 18
Date: 22-Nov-95

Table of Contents:

I. MISSOURI MED: Lyme and/or Lyme-line Disease in Missouri II. J INFECT DIS: Epidemiologic and diagnostic studies of patients with suspected early Lyme disease, Missouri, 1990-1993 III. LYMENET: Report on Human Granulocytic Ehrlichiosis IV. About The LymeNet Newsletter

Newsletter:

*********************************************************************** * The National Lyme Disease Network * * LymeNet Newsletter * ***********************************************************************

IDX# Volume 3 - Number 18 - 11/22/95 IDX# INDEX IDX# IDX# I. MISSOURI MED: Lyme and/or Lyme-line Disease in Missouri IDX# II. J INFECT DIS: Epidemiologic and diagnostic studies of IDX# patients with suspected early Lyme disease, Missouri, IDX# 1990-1993 IDX# III. LYMENET: Report on Human Granulocytic Ehrlichiosis IDX# IV. About The LymeNet Newsletter IDX#

EDITORIAL NOTE: Missouri Lyme Disease Controversy Continues

Beginning in the late 1980's, the state of Missouri has seen a dramatic increase in the number of Lyme disease cases reported to the Centers for Disease Control. However, several teams of researchers have been unable to culture Borrelia burgdorferi in Missouri from either ticks or humans. In 1990, the CDC dispatched several investigators to Missouri to work with Dr. Edwin Masters, the Cape Girardeau physician who first identified the illness, on an epidemiological study of the emerging disease.

Dr. Masters has stated unequivocally that the Missouri patients fulfill the CDC reporting criteria for Lyme disease -- an expanding lesion indistinguishable from "classic" erythema migrans; and/or late arthritic, neurologic or cardiac manifestations and seroreactivity to B. burgdorferi. The CDC maintains that the patients are not in fact seropositive and thatin the absence of successful B. burgdorferi cultures, the disease remains idiopathic.

The investigation in Missouri was marked by intense acrimony between local Missouri physicians and the CDC research team. As a result, both Dr. Masters and the Missouri State Epidemiologist, Dr. H. Denny Donnell, have refused to "sign on" as co-authors to the CDC report of the investigation, which was published in August in the Journal of Infectious Diseases. Instead, they have published their own paper in the journal Missouri Medicine. The abstracts of each paper are presented below. Readers are urged to consult the full text of each article for a more detailed understanding of the nature of this scientific dispute.

[Addendum: Earlier this year, a group of researchers led by Dr. Alan Barbour identified a suspected new Borrelia species, not yet fully characterized, in Amblyomma americanum, the suspected vector of the Missouri illness.]

I. MISSOURI MED: Lyme and/or Lyme-line Disease in Missouri ------------------------------------------------------------- AUTHORS: Masters EJ, Donnell, HD ORGANIZATION: Regional Primary Care, Inc, and Missouri Department of Health REFERENCE: Missouri Med 1995 Jul;92:346-53 ABSTRACT:

Missouri patients who fulfill the strict CDC surveillance definition for Lyme disease have been reported in significant numbers since 1989, although there are no viable Missouri human cultures of Borrelia burgdorferi. The Missouri erythema migrans rashes are indistinguishable from those in other areas, and the clinical syndrome appears similar to Lyme disease nationally. The authors suspect atypical B. burgdorferi, and/or other Borrelia spirochetes of causing this clinical borreliosis syndrome.

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II. J INFECT DIS: Epidemiologic and diagnostic studies of patients with suspected early Lyme disease, Missouri, 1990-1993 ----------------------------------------------------------- AUTHORS: Campbell GL, Paul WS, Schriefer ME, Craven RB, Robbins KE Dennis DT ORGANIZATION: Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA REFERENCE: J Infect Dis 1995 Aug;172(2):470-80 ABSTRACT:

A retrospective case-control study investigated 45 Missouri outpatients with annular rashes meeting a surveillance case definition for erythema migrans and with onset in 1990-1991. Risk factors included being male, living near a body of water, and hunting. Twenty patients (44%) associated their rash with the bite of a tick; of these, 5 described an adult Amblyomma americanum. A typical rash was described as expanding over time and measuring 8 cm in diameter at 4 days after onset. Mild constitutional symptoms were common but fever was uncommon. Serologic tests failed to incriminate Borrelia burgdorferi or selected other arthropodborne pathogens. Skin specimens from suspected erythema migrans lesions of 23 Missouri patients sampled prospectively in 1991-1993 were culture-negative for B. burgdorferi. Thus, tick bite-associated annular rashes in Missouri remain idiopathic. Possible causes include infection with a novel A. americanum-transmitted pathogen and an atypical toxic or immunologic reaction to tick-associated proteins.

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III. LYMENET: Report on Human Granulocytic Ehrlichiosis -------------------------------------------------------- Sender: Tom Grier <[email protected]>

Human Granulocytic Ehrlichiosis (A New Deadly Tick-Borne Disease)

A brief report by Tom Grier for the members of the Duluth/Superior MN Lyme Disease Support Group.

There is a newly discovered tick-borne disease in our local woods, and it lurks inside the same ticks that carry Lyme Disease. Ehrlichiosis was first described in dogs in Africa in 1935. It is only recently that a relative of this same bacteria has been found to cause a monocytic form of the disease, and more recently a granulocytic form in humans. (The term granulocytic refers to the bacterium's attachment to a type of blood cell called a granulocyte. Granulocytes are mature granular leukocytes -- neutrophils, eosinophils and basophils.). More importantly, the granulocytic form was reported by a Duluth Clinic Physician, Dr. Johan S. Bakken M.D., to be right here in our local area. (Bakken JS, Dumler JS, Chen S-M, et al. Human granulocytic ehrlichiosis in the Upper Midwest United States: a new species emerging? JAMA 1994;272:212-8.)

The first reports of suspected human ehrlichiosis were in 1986, but it wasn't until 1990 that successful techniques were developed by Jacqueline Dawson, M.S., of the Centers for Disease Control, to isolate this unique bacteria. The bacteria which was isolated in the monocytic form was Ehrlichiosis chaffeensis. The strain and species of ehrlichia causing HGE has yet to be isolated and completely characterized.

Human Granulocytic Ehrlichiosis (HGE) is caused by a strain of Ehrlichia which is more closely related to the species which cause disease in sheep and horses -- Ehrlichia pagocytophilia, and E. equis.

Tick Vectors: The possible tick vectors of HGE are Ixodes scapularis (the deer tick, or black legged tick, found in the eastern United States), and the Lone-Star tick (a tick commonly found in the southern United States).

Area of Reported Disease: The distribution of HGE mirrors that of Lyme disease. This includes the central eastern border of Minnesota and adjacent Wisconsin, the northeast United States, all of California, and the four state area surrounding Missouri.

Symptoms: HGE is transmitted from the bite of an infected tick to the human host, most probably from a deer tick bite. The symptoms come on suddenly, usually within a few days of the tick bite (range 1-30 days), perhaps even hours. The first symptoms are a flu-like syndrome of high fever 103+ (may last 10+ days), headache, a general ill feeling, muscle aches, chills, joint pain, nausea, vomiting, even breathing difficulties. Less than 1 % of cases have reported a rash in confirmed HGE. If left untreated, HGE is potentially fatal.

There have been four deaths reported. There have been over 300 confirmed cases of HGE in the USA. Concomitant infection or mixed infections from a single tick bite are possible! From a single deer tick bite it is possible to get babesiosis, Lyme disease, and HGE simultaneously. In one Rhode Island study of 116 Lyme patients, 16% were concomitantly infected with Babesia microti, the agent of babesiosis in the U.S.. Of those with mixed infection 89 % went on to develop chronic symptoms longer than six months. In Lyme disease without babesiosis, less than 7 % had symptoms beyond six months post treatment.

Treatment:

HGE - 14-21 days of tetracycline, doxycycline, or minocycline. Dosage adjusted for weight.

Babesiosis - Clindamycin and Quinine.

Testing:

Blood Smear: Three blood smears stained with Giemsa stain, and three blood smears stained with acrodine orange are used to look for bacterial inclusion bodies inside the neutrophils and lymphocytes. 700 neutrophils must be checked to rule out infection. The inclusions are called morulae. A properly trained medical technician could be taught to use blood smears as the main diagnostic tool for HGE with 85 % accuracy. (This test will also differentiate monocytic infection from granulocytic.)

IFA (Immune Fluorescent Antibody Test): The test for Ehrlichia chaffeensis is not adequate for diagnosing HGE. Patients with HGE will test antibody negative when the IFA test for E. chaffeensis is used. The HGE bacteria is more closely related to E. pagocytophilia an E.equis. 80+ % of HGE patients do test positive on IFA.

PCR. (Polymerase Chain Reaction - DNA amplification): The PCR test suffers from not having established acceptable primers of bacterial DNA to initiate the reaction. (The primer Mayo Clinic uses is the 16 S rDNA geGF/ge1Dr.) There is some cross over to other Ehrlichia species so a PCR negative result cannot rule out possible infection, and a positive does not specify monocytic ehrlichiosis vs. HGE.

What to send to the labs: One orange cap and one red cap vacuum tube of blood and six unstained blood smears. (Do Not Send Heparinized Blood!) Only two labs at this time have a commercially available test:

North American Laboratory Group 1 Lake Street New Britain, CT , 06052 For more information about testing have your doctor call at: 1-800-866-6254, or FAX 1-203-223-6279

The Duluth Clinic 400 E. 3rd St. Duluth, MN 55805 218-722-8364

Prevention: The same precautions used to prevent exposure to the ticks that cause Lyme disease, are used to diminish the risk of exposure to HGE.

HGE Tidbits -

* The bacteria is intracytoplasmic and forms aggregations or clumps called morulae.

* 43 cases in the Duluth Area since 1990. Washburn and Sawyer Counties most prevalent, with 80 and 71 cases per 100,000 population respectively. This makes HGE highly endemic and the fastest growing tick illness in the country.

* 54 % of HGE cases require hospitalization. Most patients have seizures. Fevers of 103 + last about 10 days.

* Four deaths were associated with a pneumonia infiltrate.

* The organism which causes HGE is one base pair different from E. chaffeensis, and three base pairs different from E. equis, and is probably closely related. This organism may have jumped from infected animals to man.

* Wood ticks test negative for Ehrlichia.

* The Deer ticks are not born infected. They must get the bacteria from feeding on an infected host, such as a white tailed deer (O. virginianus) which harbors the bacteria without symptoms. About 18 % of white tailed deer test positive in MN / WI.

* July is the peak month HGE is reported, but most people are probably infected in the spring.

References: J. Clin Microbiol: Chen 32:589-594, 1994 Journal of the American Medical Association "A New Species Emerging."

Lecture by Dr. Johan S. Bakken M.D. Duluth Clinic Oct, 12th 1995.

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