LymeNet Newsletter Volume 6 Issue 04

Volume: 6
Issue: 04
Date: 17-Apr-98

Table of Contents:

I. LDRC: CDC finds less Lyme but more tickborne diseases in a California community II. J Infect Dis: Seroepidemiology of emerging tickborne infectious diseases in a Northern California community. III. LYMENET: How to join the LYME-L discussion forum IV. ABOUT THE LYMENET NEWSLETTER

Newsletter:

*********************************************************************** * The National Lyme Disease Network * * http://www.lymenet.org/ * * LymeNet Newsletter * ***********************************************************************

Volume 6 / Number 04 / 17-APR-98 INDEX

I. LDRC: CDC finds less Lyme but more tickborne diseases in a California community II. J Infect Dis: Seroepidemiology of emerging tickborne infectious diseases in a Northern California community. III. LYMENET: How to join the LYME-L discussion forum IV. ABOUT THE LYMENET NEWSLETTER

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I. LDRC: CDC finds less Lyme but more tickborne diseases in a California community ---------------------------------------------------------------- Reprinted from the Lyme Times, Number 19, November / December 1997

The headline in the January 10, 1995, Sonoma Index-Tribune proclaimed, "Community A [name changed] not a hot spot for tickborne Lyme disease" - and the community breathed a sigh of relief. But was it really such good news? A recently completed CDC research study found that almost one quarter of the study participants had tested positive for at least one of three tickborne diseases. And if the humans weren't testing positive for Lyme disease in great numbers, an astounding 37% & the local dogs did - but then the dogs were not subjected to the rigid two tier Centers for Disease Control and Prevention (CDC) testing protocol, and when dogs get sick, no one calls them hypochondriacs.

Approximately 450 residents live in the semirural community in Sonoma County in northern California, and 230 participated in the serologic study. Fifty-one tested positive for one or more of three tickborne disease agents: Lyme disease, ehrlichiosis, and babesiosis. Half of the children in the study tested positive. Researchers from the CDC along with University of California scientists and health department personnel report the results in the June issue of the Journal of Infectious Diseases. (1)

The Sonoma study was initiated by a local mother and horse-owner Susie Merrill. She had participated in a Lyme disease study of her neighborhood, working with state and county biologists to trap rodents and drag for ticks. She conducted a phone survey and marked suspected Lyme disease cases, including on her map dogs that had tested positive for Lyme disease.

Maybe ehrlichiosis was to blame

Merrill's son had been diagnosed with Lyme disease in 1991, and had not totally recovered after treatment. Several of Merrill's horses and her dog had also been diagnosed with ehrlichiosis. Merrill began to wonder if chronic Lyme disease really was the cause of her son's continuing headaches and other symptoms. Maybe ehrlichiosis was the culprit. Perhaps it was responsible for the chronic symptoms of some of her neighbors, too. At the time, ehrlichiosis was not thought to infect humans.

Merrill went back to the phone and called the neighbors again. As she collected information, she became convinced that more than one tickborne disease was being diagnosed as Lyme disease. When she plotted the cases of ehrlichiosis on her map, she noticed that sick people seemed to be clustered near infected animals - but the animals were infected with ehrlichiosis, not Lyme.

Merrill battles for recognition

Merrill's initial entreaties to public health agencies to investigate the situation in her community fell on deaf ears. For the next two years, she badgered health officials, enlisting the support of her senators and congresspeople with a barrage of letters. Finally the CDC agreed to assist the state and county health agencies in conducting a study. The published results now suggest that Merrill's hunch was correct. Samples from 23% of the residents were seroreactive to antigens from one or more tickborne disease agents: 1.4% to Borrelia burgdorferi, 0.4% to Ehrlichia equi, 4.6% to Ehrlichia chaffeenis, and 17.8% to the Babesia-like piroplasm WA1. Some scientists are raising questions about the study conclusions, however. The incidence of Babesia is very high, raising suspicions about the test, which is quite new. Then the researchers report an incidence of Lyme disease barely over the 1% generally considered as background seropositivity in a control group. Serosurveys in endemic areas have typically reported much higher incidences. An
epidemiologic study of a community in Mendocino County found 24% of the inhabitants had positive Lyme disease tests. (2) Many were symptomatic at the time and more have developed symptoms since, including psychosis and pancarditis. Later tests of that community also showed two percent positive for babesiosis, an unrecognized human disease in this area at the time of the original serosurvey (unreported data).

The results of the Sonoma dog study are intriguing, also, although the dog data were not included in the present study. If the same ticks were biting both dogs and humans, it is curious that such a low percentage of humans were apparently acquiring the Lyme disease bacterium, when, judging by the ehrlichiosis and babesiosis figures, many of them were in fact being bitten by ticks. The dog sera were tested by Rance LeFebvre, PhD, at the University of California laboratory in Davis.

ELISA was used as screening test

Initially, community residents had to pass a screening blood test before being allowed to participate in the study. This blood test, an ELISA, has been criticized for its lack of, sensitivity, i.e. many true cases of Lyme disease test negative. According to the College of American Pathologists Proficiency Testing Program, which receives samples from every laboratory in the United States, current screening tests are inadequate. In a paper published in March, researchers concluded that "the sensitivity and specificity of the currently used tests [ELISA or IFA] for Lyme disease are not adequate to meet the two-tier approach being recommended [by the CDC]. Ideally a screen test should have a high degree of sensitivity (>95%)." The data showed that the sensitivity of the ELISAs fluctuated between 75 and 93%. (3) Further, participants who may have been seronegative were not counted, although the researchers acknowledge that they may have existed in the population sample. Several investigators have estimated
seronegativity in both early or chronic Lyme disease at 17 to 29.4% of patients. (4)(5)(6) The low figure for Lyme disease reported in the present study may be partly attributable to the use of the restrictive CDC testing criteria, which were intended for surveillance purposes and not for clinical diagnosis. It may also be related to the study's use of the B31 strain of Borrelia burgdorferi used as antigen, although the researchers claim to have observed no difference in the interpretation of reactivity. The Mendocino study found a 20% discrepancy between sera tested B31 and CA5 when people infected with the California strain were tested against the B31 Shelter Island, NY, strain, and vice versa. (7)

After the study was underway, Merrill complained in a letter to Dr. Duc Vugia, study collaborator and Chief of the Disease Investigations and Surveillance Branch at California Department of Health Services, that many of her neighbors had had a positive test for Lyme disease in the past, but not in this study. They had also responded to treatment for Lyme disease. She was concerned that these people had Lyme disease but were being dropped from the study since they did not meet the entry criteria.

CDC principal investigator Curtis Fritz didn't see it that way. At an interview after one of the community meetings for participants, he assured residents, "Ninety-five percent of the people who have been diagnosed with late Lyme disease but with negative antibody tests in fact have never had Lyme disease." He also claimed that the CDC test was much better than those of commercial laboratories. In a recent controversial paper, the CDC reported a 100% sensitivity, 89% specificity of their in-house ELISA test, exceeding previously reported standards. (8)

People who passed the first screening test had additionally to pass a second test, the Western Blot, in order to be considered positive for Lyme disease. This test is sensitive, but the official criteria for a positive are very restrictive, and are still being debated in medical circles. Criteria may be overly restrictive

Dr. [Nick] Harris, president of IGeneX, a laboratory in Palo Alto, California, which specializes in Lyme disease testing, points out that different patterns of reactivity and levels of antibody may be seen in confirmed Lyme disease cases, but these were not considered in the study. Other experts feel that it is premature to apply such restrictive criteria to a disease whose clinical spectrum is still being defined. Many agree standards used for surveillance are not appropriate for clinical diagnosis.

No physical examinations were done to corroborate serologies, no attempt was made to gather additional serologic data on people who were symptomatic but ELISA negative, and no Western blots were obtained on ELISA-negative people, although some investigators have found Western Blot positive/ELISA negative patients. (9)(10)

In addition, the questionnaire utilized in the study instructed participants to skip over questions about symptoms if they had not been diagnosed with Lyme disease.

"Even if people previously had symptoms of Lyme disease, some have never been diagnosed with it, so they would have skipped these questions," claims Merrill.

Nymphal tick infection rate may be much higher

This study assumed a low (1 to 2%) infection rate among ticks found in the neighborhood. While this figure reflects early assessments of adult ticks in California, it is at variance with newer reports on Ixodes pacificus nymphs, which are considered to be the main vectors of Lyme disease to humans. Some parts of Mendocino and Sonoma Counties have a reported nymphal tick infection rate as high as 14%. (11)

Dr. Fritz tried to mitigate public fears by assuring people that seronegative late Lyme disease after treatment is a rare phenomenon and that the chances of acquiring a tickborne disease are low. Some residents of the Sonoma community accepted his assurances, while others did not. Some worried that the neighborhood would be labeled as a Lyme disease hot spot, adversely affecting real estate values.

However several were appreciative of Merrill's efforts to educate their community. Linda Marmaduke, one of Merrill's neighbors, said, "This study was done after many people became ill, some chronically, with undiagnosed or incorrectly diagnosed illnesses. Susie Merrill was instrumental in bringing this disease to the public's attention. If she had not shared her knowledge with others, my daughter. for one, would not have received adequate and prompt treatment."

Perhaps it was an oversight that the study authors did not acknowledge Merrill's initiative in instigating the study, nor her work guiding biologists around the area and organizing community meetings. They omitted her name from the unusually lengthy list of acknowledgments at the end of their article. Still, it is curious, since certainly without Merrill's persistence, no Sonoma study would have been done, and without her help as liaison, community participation probably would have been significantly curtailed.

Since the early l980s, over 1400 cases meeting the strict CDC case surveillance definition have been reported from California. This figure is artificially low even for surveillance because many physicians do not bother to report their cases since they will not meet the case definition anyway. (12) In addition, many West Coast physicians still deny even the possibility of Lyme disease thinking of it as an East Coast disease, in spite of the fact that biologists with the California Department of Health have found the vector in all but two of the California counties, and infected ticks in more than half of those. (13)

This new study opens anew the debate about the risk of acquiring a tickborne disease in northern California. The Sonoma study concluded, "The risk of infection with these emerging tickborne diseases may be greater than previously recognized... particularly in children." (14)

REFERENCES: (1) Fritz CL, et al. Seroepidemiology of emerging tickborne infectious diseases in a Northern California community. http://search.lymenet.org/domino/abstract.nsf/UID/97323987 (2) Lane RS, et al. Risk factors for Lyme disease in a small rural community in northern California. http://search.lymenet.org/domino/abstract.nsf/UID/93142776 (3) Bakken LL, et al. Interlaboratory comparison of test results for detection of Lyme disease by 516 participants in the Wisconsin State Laboratory of Hygiene / College of American Pathologists Proficiency Testing Program. http://search.lymenet.org/domino/abstract.nsf/UID/97193799

(4) Engstrom SM, et al. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. http://search.lymenet.org/domino/abstract.nsf/UID/95229937

(5) Oksi J, et al. Antibodies against whole sonicated Borrelia burgdorferi spirochetes, 41-kilodalton flagellin, and P39 protein in patients with PCR- or culture-proven late Lyme borreliosis. http://search.lymenet.org/domino/abstract.nsf/UID/96025135

(6) Shadick, et al. The long-term clinical outcomes of Lyme disease. A population-based retrospective cohort study. http://search.lymenet.org/domino/abstract.nsf/UID/94367953

(7) Lane RS, et al. Risk factors for Lyme disease in a small rural community in northern California. http://search.lymenet.org/domino/abstract.nsf/UID/93142776

(8) Tugwell P, et al. Laboratory evaluation in the diagnosis of Lyme disease. http://search.lymenet.org/domino/abstract.nsf/UID/98049722

(9) Cameron D. Non-confirmed ELISA Testing for Lyme Disease: Bayes' Theorem Consideration. VII Int Congr Lyme Borreliosis, 1996, Abs E804.

(10) Kochvar JM, Liegner K. Simultaneous ELISA and Western Blot Testing in Evaulation of Patients for Suspected Lyme Disease. 10th LDF Conf, 1997, Poster.

(11) Clover JR, et al. Evidence implicating nymphal Ixodes pacificus (Acari: ixodidae) in the epidemiology of Lyme disease in California. http://search.lymenet.org/domino/abstract.nsf/UID/96033004

(12) Murray RM, CDHS epidemiologist, personal communication.

(13) Clover JR, CDHS Senior Biologist, map, 1994.

(14) Fritz CL, et al. Seroepidemiology of emerging tickborne infectious diseases in a Northern California community. http://search.lymenet.org/domino/abstract.nsf/UID/97323987

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II. J Infect Dis: Seroepidemiology of emerging tickborne infectious diseases in a Northern California community. ------------------------------------------------------------- AUTHORS: Fritz CL, Kjemtrup AM, Conrad PA, Flores GR, Campbell GL Schriefer ME, Gallo D, Vugia DJ ORGANIZATION: Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA. REFERENCE: J Infect Dis 1997 Jun;175(6):1432-9 ABSTRACT:

A seroprevalence and risk factor study of emerging tickborne infectious diseases (Lyme disease, ehrlichiosis, and babesiosis) was conducted among 230 residents of a semirural community in Sonoma County, California. Over 50% of residents reported finding a tick on themselves in the preceding 12 months. Samples from 51(23%) residents were seroreactive to antigens from one or more tickborne disease agents: 1.4% to Borrelia burgdorferi, 0.4% to Ehrlichia equi, 4.6% to Ehrlichia chaffeensis, and 17.8% to the Babesia-like piroplasm WA1. Only 14 (27%) of these seroreactive residents reported one or more symptoms compatible with these diseases. Seroreactivity was significantly associated with younger age (<16 years), longer residence in the community (11-20 years), and having had a physician's diagnosis of Lyme disease. In northern California, the risk of infection with these emerging tickborne diseases, particularly in children, may be greater than previously recognized.

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III. LYMENET: How to join the LYME-L discussion forum ------------------------------------------------------ Sender: Siegfried Schmitt <[email protected]> LYME-L is a discussion forum for researchers who are interested in diagnosis, treatment, and prevention of Lyme disease. If you want to join LYME-L, you should send the command:

sub lyme-l Your_first_name Your_last_name

via e-mail to

[email protected]

If you want to know more about LYME-L, please contact

[email protected] (Siegfried Schmitt)

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