The Lyme Wars

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  1. dontlikeliver

    dontlikeliver New Member

    The Lyme Wars - time to listen
    1. Introduction
    2. Assertions and comments
    3. Expert opinion and conclusion

    Raphael B Stricker† & Andrew Lautin
    †Department of Medicine, California Pacific Medical Center, San Francisco, CA, USA

    Lyme disease represents a public health threat of major proportions. The murky science and acrimonious politics of Lyme disease have created barriers to reliable diagnosis and effective treatment of this protean illness.

    Two major clinical problems with the disease are the absence of a therapeutic end point in treating Borrelia burgdorferi, the spirochetal agent of Lyme disease, and the presence of tick-borne co-infections such as Babesiosis, Anaplasmosis and Bartonellosis that may complicate the course of the illness.

    From a pathophysiological standpoint, the affinity of B. burgdorferi for multiple cell types and the presence of non-replicating forms of the spirochete have contributed to persistent infection and failure of simple antibiotic regimens. Newer approaches to the treatment of Lyme disease should take into account its clinical complexity in co-infected patients and the possible need for prolonged combination therapy in patients with persistent symptoms of this potentially debilitating illness. The risk and prevention of human transmission of Lyme disease merit further study.

    Keywords: Anaplasma, Babesia, Bartonella, Borrelia, co-infections, Lyme disease

    Expert Opin. Investig. Drugs (2003) 12(10)
    1. Introduction
    Virtually from the moment of its discovery in 1975, Lyme disease has been a controversial illness [1,2]. The controversy is grounded in the murky nature of the disease, from its protean manifestations and inconsistent diagnostic parameters to its uncertain treatment. In addition to these scientific inconsistencies, the politics surrounding Lyme disease rivals the worst medical defamation in history, from syphilis (always the ‘other country’s venereal disease’) to AIDS (the ‘scourge of alternative lifestyles’).

    Perhaps the political apogee of Lyme disease came in 1993, when Joseph Burrascano testified before the US Congress that Lyme disease was not "hard to catch and easy to cure", as others had reassured the government. Rather, the disease was an underreported and growing menace that would exact a huge toll on the healthcare system if policy did not change [3,4]. For his efforts, Burrascano was prosecuted by his state medical board and the ‘Lyme Wars’ have become even more acrimonious.

    What sustains this controversy? It is important to recognise that the science of Lyme disease suffers from two major problems. First, there is no test currently available that proves the eradication of Borrelia burgdorferi, the spirochetal agent of Lyme disease, from the human body [5,6]. Conversely, there is growing evidence for longterm persistence of the Lyme disease spirochete in animal models [7-11] and humans [12-14] despite alleged adequate treatment for the disease.

    The second problem is that Lyme disease likes company, and over the past 20 years we have seen compelling evidence for co-infections transmitted by ticks (which have been called ‘sewers of infectious disease’) along with the Lyme disease spirochete [15-21]. Thus, the term ‘Lyme disease’ often signifies a poorly characterised polymicrobial infection with no fixed end point.

    This nebulous infectious disease presents a nightmare scenario for both the victim of Lyme disease and any rational healthcare provider who must deal with the complex implications of the tick-borne illness. A corollary to this nightmare is the growing recognition of possible spread of the Lyme disease spirochete by human contact [22,23].

    With this background, the article by Charles Pavia [24] on current and novel therapies for Lyme disease is yet another trivialising treatise that presents inaccurate or incorrect information about this potential nightmare. In our view, the banality of the article reflects an entrenched and growing ignorance and neglect of the severity of Lyme disease, while its victims continue to suffer. Below is a partial rundown of points presented in the article with which we strongly take issue. We have listed these points in their order of appearance and appended our corresponding commentary.

    2. Assertions and comments
    Assertion (1): B. burgdorferi can be readily cultivated in vitro using special culture medium.
    Comment (1): B. burgdorferi is difficult to culture by routine methods, and virtually no clinical laboratory can perform this basic infectious disease test [25,26]. This clinical drawback has severely limited the diagnosis of Lyme disease. A similar problem is seen with syphilis, an illness caused by the spirochete Treponema pallidum. Since this organism cannot be cultured in vitro, the diagnosis of syphilis (like Lyme disease) is supported by serological testing, prompting the observation that ‘any infection for which diagnosis and assessment of treatment response depend on serologic testing is one in which clinical certainty is elusive’ [27].

    Assertion (2): About 20 – 25% of Lyme disease patients do not remember developing a characteristic ‘bullseye’ erythema migrans (EM) rash.

    Comment (2): According to recent health department statistics from Texas, Connecticut and California, the EM rash fails to appear in 41 – 65% of Lyme disease patients, and recognition of the rash may be even lower depending on the location of the tick-bite and the awareness of the person who was bitten [28,101]. The published incidence of the EM rash also reflects a type of circular reasoning that pervades Lyme disease research: since the presence of an EM rash is the best evidence for Lyme disease, it has become the most common criterion for admission into Lyme disease studies. Since most patients in these studies have an EM rash, the incidence of the rash becomes inflated in the medical literature. The literature then perpetuates the myth that the vast majority of Lyme disease patients have an EM rash [4,22].

    Assertion (3): The Lyme enzyme-linked immunosorbent assay (ELISA) is the preferred method to diagnose Lyme disease due to its sensitivity, adaptability to automation and ease of quantitation.

    Comment (3): The Lyme ELISA misses at least 50% of Lyme disease cases due to the assay’s insensitivity and variability with antibiotic treatment [101]. It follows that the two-tiered testing system endorsed by the US Centers for Disease Control and Prevention (CDC), which includes an ELISA screening test followed by a confirmatory Western blot, will also miss 50% of Lyme disease cases because a positive ELISA result is required to proceed to the confirmatory Western blot test [28,101]. Parenthetically, the CDC criteria were developed for surveillance of Lyme disease, not for diagnostic purposes. This is an important distinction because it is inappropriate to apply surveillance criteria to symptomatic patients whose clinical picture already suggests the presence of Lyme disease. Thus, there is currently no sanctioned, standardised, consistent serological test for Lyme disease in the US [28,101].

    Assertion (4): Only motile forms (of B. burgdorferi) are considered to be viable and capable of replicating.

    Comment (4): B. burgdorferi assumes different forms in different hosts [29-35]. The most troublesome is the so-called cyst form that may lie dormant in the human host, thus evading antibiotic therapy that targets replicating bacteria [29-33]. The non-replicating cyst form is undoubtedly the key to persistence of infection with the Lyme disease spirochete, and any antibiotic approach to Lyme disease that fails to recognise this pathogenic entity is doomed to failure [34,35].

    Assertion (5): The Lyme disease vaccine was withdrawn due to lack of public interest.

    Comment (5): The GlaxoSmithKline Lyme vaccine (LYMErix™) was withdrawn in the face of a class action lawsuit involving > 300 patients who claim that they developed a ‘Lyme-like’ illness after receiving the vaccine.

    Assertion (6): Early Lyme disease is readily treatable with a 2 – 3 week course of antibiotics.

    Comment (6): This statement is misleading for several reasons. First, ‘early Lyme disease’ often goes undetected due to lack of awareness of a tick-bite and absence of an EM rash [28]. Second, recent studies have shown that tick saliva carries immunosuppressive substances that allow tick-borne agents to invade tissues while paralysing the local immune response [36,37]. Thus, the Lyme disease spirochete may rapidly disseminate and become entrenched and resistant early in the disease (see below) [38-40]. Third, co-infections may alter the course of ‘early Lyme disease’, and these co-infections may make the Lyme disease patient more difficult to treat (see below).

    Assertion (7): To date, there is no evidence for the existence of any antibiotic-resistant strains of B. burgdorferi’.

    Comment (7): A serious understatement. B. burgdorferi is an extremely complex organism. The Lyme disease spirochete contains at least 132 functioning genes, in contrast to T. pallidum, the spirochete that causes syphilis, which contains only 22 such genes [41]. Although B. burgdorferi may not be ‘resistant’ to antibiotics by conventional laboratory methods, we know that the spirochete can enter cells such as fibroblasts, synovial cells, endothelial cells and macrophages [42-47]. In these cells, B. burgdorferi becomes functionally resistant to treatment, partly due to ‘camouflage’ proteins produced by the organism or adsorbed from the cell and partly due to the altered morphology and replication of the spirochetal cyst form (see above) [34,40,43]. This functional resistance leads to persistent infection despite supposedly adequate treatment for Lyme disease. The immune evasion strategy of B. burgdorferi is reminiscent of mycobacterial infections such as tuberculosis or leprosy [38-40].

    Assertion (8): It is unclear whether a concurrent Anaplasma or Babesia infection can influence the outcome of a standard course of treatment for Lyme disease.

    Comment (8): Animal models of co-infection with B. burgdorferi and either Babesia microti or Anaplasma phagocytophila (the agent of human granulocytic ehrlichiosis) have demonstrated an altered immune response and clinically worse disease in these animals [48-50]. Similar exacerbation of clinical symptoms and resistance to treatment has been observed in humans [16,51].

    Assertion (9): A single dose of doxycycline given within 72 h after a recognisable tick-bite was highly effective in preventing early Lyme disease.

    Comment (9): The study that showed the alleged benefit of prophylactic single-dose doxycycline had inadequate follow up to prove the absence of clinical infection following this simple treatment [52]. Furthermore, the authors used development of an EM rash as an end point in the study. Since 41 – 65% of Lyme disease patients do not develop an EM rash, the study may have missed more than half the patients who eventually came down with Lyme disease after this theoretically inadequate prophylaxis. The use of single-dose doxycycline also raises concern about antibiotic resistance following this microbiologically unsound therapy.

    Assertion (10): Healthcare providers who deal with Lyme disease can be divided into two groups: ‘specialists’ who are often affiliated with ‘large academic institutions’, versus ‘community-based’ providers in ‘private (family) practice’. The former group tends to adhere to the guidelines of the CDC and the Infectious Disease Society of America (IDSA) in diagnosing and treating Lyme disease. In contrast, the latter group tends to rely on ‘anecdotal reports citing an alarming number of Lyme disease patients who are supposedly co-infected with one or more of the following: Anaplasma, Bartonella or Babesia. Such an unlikely scenario of multiple infections arouses suspicion on the authenticity of these cases and those willing to make such diagnoses’.

    Comment (10): We feel that this is a very politically charged statement, featuring two issues that define the Lyme Wars. The first issue concerns the lofty ‘academic specialists’ who follow the CDC and IDSA guidelines in diagnosing and treating Lyme disease. We have seen that the CDC guidelines give a poor diagnostic yield for Lyme disease, since they were meant for surveillance purposes and not for diagnosis [22,101]. The IDSA guidelines were written by a panel of 12 Lyme disease ‘experts’, 11 of whom were research scientists with minimal clinical experience in treating Lyme disease. These guidelines have doomed thousands of suffering Lyme disease patients to a lack of therapy based on the opinions of a handful of researchers. With this knowledge, is it any wonder that ‘communitybased’ providers who deal with the clinical nightmare of Lyme disease have rejected the CDC/IDSA guidelines and formulated their own diagnostic and therapeutic parameters [53-55]? Pavia raises the second issue based on this clinical dichotomy, stating that Lyme disease treatment outside the CDC/IDSA guidelines represents a provider-driven policy that impugns the integrity of the provider. The reality is that suffering patients seek out ‘Lyme-literate ’ providers because the ‘academic’ researchers have abandoned them. These researchers and their followers offer nothing in the way of treatment for the suffering of Lyme disease patients other than pseudopsychiatric semantics [4,22] or meaningless labels such as chronic fatigue syndrome or fibromyalgia, which are often manifestations of chronic, poorly treated Lyme disease [56,57]. Pavia also refers to the alarming number of Lyme disease patients who are supposedly co-infected with other tick-borne organisms. Since this number is now ~ 20% or more of all Lyme disease cases [18,20,29], the alarm should have sounded long ago.

    Assertion (11): The Pavia paper praises the ‘highly significant’ results of the study by Klempner et al. [58] that examined retreatment of Lyme disease patients who had persistent symptoms of the disease. The study claimed that it is unlikely that prolonged antibiotic treatment will offer any major benefit to symptomatic patients who are no longer infectious.

    Comment (11): The study by Klempner et al. [58] has been analysed in detail elsewhere [55,102]. At the beginning of this article, we noted that one of the main problems with Lyme disease is the lack of a test that proves the eradication of spirochetal infection. Thus, we feel that the design of the study by Klempner et al. was basically flawed, since the culture and molecular techniques used in the study were insufficient to prove that patients were ‘no longer infectious’ [102]. Furthermore, the choice of ‘prolonged’ antibiotic therapy for patients with neurological disease (1 month of intravenous ceftriaxone followed by 2 months of low-dose oral doxycycline) was irrational and doomed to failure [55,102]. Consequently, the study simply shows that inadequate retreatment of chronic Lyme disease leads to inadequate results [102].

    Unfortunately, because of the widespread publicity given to this article and its prestigious publisher, the flawed data has been widely used to deny care for symptomatic subjects.

    Assertion (12): Pavia focuses on hyperbaric oxygen therapy (HBOT), shorter course treatment with antibiotics and evernimicin therapy as future treatment options for Lyme disease.

    Comment (12): HBOT is currently being used as adjunctive treatment for chronic Lyme disease [101]. Although in theory it is effective in creating a more hostile environment for the Lyme disease spirochete, HBOT is a cumbersome procedure that probably will never be available to the majority of patients with chronic infection. The cost of multiple treatments is also prohibitive. The Pavia paper fails to address the hepatic toxicity of evernimicin, and it is doubtful that this toxic antibiotic will ever be marketed for Lyme disease. Shorter course antibiotic therapy was the subject of a recent study [59], and this minimalist approach promises to yield more inadequately treated Lyme disease sufferers. In contrast to these impractical or potentially toxic treatment options, current and future Lyme disease therapy should focus on combinations of antibiotics that are readily available and administered in a rational manner, with monitoring of clinical and immunological parameters [53,60-62]. In this regard, it is important to remember that the current World Health Organization (WHO) recommendation for treating infection with Mycobacterium tuberculosis is a combination of two antimicrobial agents administered for 18 months, while the WHO-sanctioned treatment for leprosy is a combination of three antimicrobial agents administered for 2 years [63-65]. For a spirochete as complex and crafty as B. burgdorferi, these guidelines are probably closer to what is needed for the eradication of chronic spirochetal infection in Lyme disease. As stated previously, recognition and evaluation of human transmission of Lyme disease will also play a role in developing effective treatment strategies [22,23].
    3. Expert opinion and conclusion
    In conclusion, Lyme disease remains a public health threat of major proportions. Continued trivialisation of this complex spirochetal illness only serves to augment the threat by legitimising ignorance of Lyme disease and neglect of Lyme disease patients. Until this trend is reversed, we will continue to see thousands of patients suffering at the hands of the medical establishment and desperately seeking care from the few providers who will listen. As modern medicine rockets into the 21st Century, this ostracism of suffering patients and persecution of dissenting healthcare providers can no longer be tolerated. For their part, Lyme disease patients and their providers must learn from the AIDS experience, where activism brought change when it was perceived that nobody was listening. And as more people listen, the ‘Lyme Wars’ may finally reach an end.

    The authors thank Robert Bransfield, Joseph Burrascano, Kathleen Dickson, David Dorward, Brian Fallon, Andrea Gaito, Julie Gerberding, Nick Harris, William Harvey, Barbara Johnson, Anne Kjemtrup, Robert Lane, Kenneth Liegner, Robert Lull, Daniel Moore, Scott Morrow, Steven Phillips, Walter Prehn, Lynn Shepler, Virginia Sherr, Harold Smith, Gerald Sugarman and Edward Winger for helpful discussion.
    We also thank Pat Smith of the Lyme Disease Association, Phyllis Mervine, Lee Lull, Peggy Leonard and Barb Barsocchini of the California Lyme Disease Resource Center and Karen Forschner of the Lyme Disease Foundation for continuing support. This article is dedicated to the memory of Paul Lavoie.

    Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.
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    61. STRICKER RB, BURRASCANO J, WINGER EE: Longterm decrease in the CD57 lymphocyte subset in a patient with chronic Lyme disease. Ann. Agric. Environ. Med. (2002) 9:111-113.
    62. STRICKER RB, WINGER EE: Normalization of the CD57 natural killer cell subset associated with prolonged antibiotic therapy in patients with chronic Lyme disease. Clin. Immunol. (2002) 103:S117-S118.
    63. SMALL PM, FUJIWARA PI: Management of tuberculosis in the United States. N. Engl. J. Med. (2001) 345:189-200.
    64. SHAW IN, NATRAJAN MM, RAO GS, JESUDASAN K, CHRISTIAN M, KAVITHA M: Long-term follow up of multibacillary leprosy patients with high BI treated with WHO/MDT regimen for a fixed duration of two years. Int. J. Lepr. Other Mycobact. Dis. (2000) 68:405-409.
    65. GOTO M: Chemotherapy of leprosy: theoretical basis of new guideline in Japan. Nihon Hansenbyo Gakkai Zasshi (2001) 70:151-155.
    Lots of links on Lyme disease - over 12,000 categorised links on Lyme disease (2001).
    •• The most extensive collection of Lyme disease references in existence.
    PHILLIPS SE, BRANSFIELD R, SHERR VT et al.: Evaluation of antibiotic treatment in patients with persistent symptoms of Lyme disease: an ILADS position paper (2003).
    •• A comprehensive critique of [58], the flawed study of ‘long-term’ antibiotic therapy for Lyme disease.
    Raphael B Stricker MD1† & Andrew Lautin2 †Author for correspondence
    1†Department of Medicine, California Pacific Medical Center, 450 Sutter Street, Suite 1504, San Francisco, CA, USA
    Tel: +1 415 399 1035; Fax: +1 415 399 1057; E-mail:
    2Department of Psychiatry, New York University School of Medicine, New York, NY, USA

    Contents of this Web Site are for the purpose of information and education only,
    and not a guide to diagnosis or treatment of a particular disorder or its symptoms.


    ANNXYZ New Member

    think this sounds far more realistic than the CDC spin
    on lyme disease .
  3. Jeanne-in-Canada

    Jeanne-in-Canada New Member

    this webpage is from Health Canada archives and contains several pages of other Lyme articles, research junkies will want to check this address out}

    this report has a specific case report of tic-borne coinfection w/ lab results and treatment, very thorough, though 7 yrs old
    Government of Canada Public Health Agency of Canada / Agency de la santé publique du Canada

    Public Health Agency of Canada (PHAC)
    Canada Communicable Disease Report

    Volume 24-12
    June 15, 1998



    Human babesiosis (caused by Babesia microti) and Lyme disease (caused by Borrelia burgdorferi) are among the most common tick-transmitted zoonoses. Recent evidence indicates that both diseases are emerging in the northeastern and Great Lakes regions of the United States as the deer tick (Ixodes scapularis), which transmits both infections, increases in geographic distribution(1,2). Because B. microti and B. burgdorferi reside in the same rodent reservoir (Peromyscus leucopus) and are transmitted by the same tick vector, human co-infection may be relatively common in endemic areas. In support of this contention, up to two-thirds of Long Island residents with Lyme disease have antibodies to Babesia species(3). However, until recently, only three episodes of co-infection had been described and, in each case, a particularly severe illness was experienced and one individual died(4-6). A recent report from New England found that the severity of symptoms and duration of illness in patients with concurrent babesiosis and Lyme disease was greater than for either infection alone(7).

    Ixodes scapularis ticks have been found in a number of provinces in Canada and 205 cases of Lyme disease were reported to public-health officials from 1984-1994 (105 locally acquired)(8). However, there have been no previous reports of co-infections in Canada and, to our knowledge, no case of babesiosis has ever been reported in Canada. This report describes a co-infection of babesiosis and Lyme disease acquired by a Canadian traveler.

    Case Report

    A 59-year-old male from Toronto presented to The Toronto Hospital on 27 July 1997 because of persistent fever and night sweats. The patient had recently returned from a 6-week trip to Nantucket, where he had vacationed in a summer home. There was no history of rural travel nor hiking or walking in the woods. Additional travel history included a trip to Hong Kong, Indonesia, and Singapore 7 months ealier.

    The patient was well until 21 June 1997 when he noticed a small black "pinhead" lesion on his left biceps, which he removed. He subsequently developed a spreading erythema surrounding this lesion that spontaneously resolved after 2 to 3 days. On 26 June, he experienced a 2-day episode of fever, sweats, chills, myalgia, and fatigue, which was treated symptomatically with acetaminophen. He was then well until 21 July 1997 when the fever and chills returned. In addition, he developed rigors, extreme fatigue, headache, myalgia, nausea, vomiting, and drenching night sweats. On 22 July, he saw his family physician who diagnosed a "viral infection". On presentation to The Toronto Hospital 5 days later, he was febrile (38.8o C), pale, and appeared ill. He had a tachycardia of 130 beats/minute, mild splenomegaly, and occasional petechia on his extremities. The remainder of his examination was unremarkable.

    Initial laboratory investigations revealed a normochromic, normocytic anemia of 106 g/L, leukopenia of 4.2 billion/L (normal 4.5 to 11.0), thrombocytopenia of 14 billion/L (normal 150 to 400), elevated lactate dehydrogenase at 799 U/L (normal 45 to 90), bilirubin 26 µmol/L (normal 2 to 17), aspartate aminotransferase 151 U/L (normal < 35), fibrinogen 4.22 g/L (normal 1.5 to 3.5), fibrin degradable products > 10 µg/mL (normal < 2.5), international normalized ratio 4.89 (normal 1.00), decreased haptoglobin < 0.12 g/L (normal 0.6 to 2.9), and D-dimers < 250 ng/mL (normal 500 to 1,000). Urinalysis was positive for blood and hemoglobin.

    His past medical history was significant for nephritis of unknown etiology at the age of 3 years, atrial fibrillation diagnosed in 1995, and a myocardial infarction in 1996 complicated by congestive heart failure. He had not previously undergone splenectomy nor had he ever received a blood transfusion. The patient's medications included coumadin 7.5 mg po od, cozaar 50 mg po od, lanoxin 0.125 mg po od, and acetylsalicylic acid 325 mg po od. He had no known allergies.

    His travel history to southeast Asia, fever, and hemolytic picture suggested malaria; thick and thin films were ordered. Thick and thin films revealed many tiny ring forms, initially interpreted as Plasmodium falciparum malaria at 4% parasitemia. However, an astute senior technologist noted morphologic differences from P. falciparum malaria and correctly identified the protozoan organisms on the smears as trophozoites of B. microti.

    Given the severity of his illness and the preceding rash consistent with erythema migrans, there were concerns of a co-infection with additional tick-borne agents. Lyme serology was ordered and reported as positive by enzyme-linked immunoabsorbent assay and IgM positive by specific Western blot test indicating a recent infection with B. burgdorferi. Serology for human monocytic ehrlichiosis (HME), caused by Ehrlichia chaffeensis, was reported as negative at 1:64 by immunofluorescence assay. Polymerase chain reaction assays for the agent associated with human granulocytic ehrlichiosis (HGE), caused by Ehrlichia equi-like organisms, were performed in our laboratory and were negative(9).

    The patient was treated with quinine 600 mg tid and clindamycin 600 mg tid for 7 days for the babesial infection and doxycycline 100 mg bid for 21 days for Lyme disease. He responded promptly to therapy and was smear negative by the fourth day. When seen in follow-up at 1 and 2 months, he was asymptomatic, all previous biochemical and hematologic abnormalities returned to normal, and smears for babesiosis were negative.


    This case represents the first description of human babesiosis and the first report of a co-infection with Lyme disease recognized in Canada. Human babesiosis in the northeast and Great Lakes regions of the United States is caused by B. microti, an intracellular parasite that may be confused with P. falciparum malaria both clinically and morphologically, as initially occurred in this case(10). The morphologic features that permit discrimination from malaria include the presence of paired piriform stages and a tetrad configuration ("Maltese cross") formed by binary fission of the trophozoite to form four merozoites. These later forms are diagnostic for babesiosis but may be difficult to find. The absence of pigment and gametocytes in babesiosis may also be helpful distinguishing features. A new species of babesiosis (WA-1) which is morphologically identical to B. microti has been described on the west coast of the United States and in Missouri(11,12). The nymph stages of I. scapularis are primarily responsible for transmission of both Lyme disease and babesiosis.

    The nymph is < 3 mm long even when fully engorged, and most infected persons do not remember a tick bite(13). It is probable that the small pinpoint lesion removed by the patient in this case was in fact an engorged nymphal-stage tick. Nymphs typically feed more actively in May and June resulting in a peak of clinical illness in July. As in this case, symptoms of babesiosis usually begin 1 to 4 weeks after a tick bite(13). The clinical spectrum ranges from a mild, self-limited illness to a serious life-threatening infection with severe hemolytic anemia, thrombocytopenia, renal failure and hypotension(13). Mortality rates in the United States have been < 10%, and deaths more common in the elderly, those with splenectomy, and those with HIV infection(13,14).

    Co-infection with other tick-borne agents has recently been recognized as an important determinant of the outcome of infection with babesiosis. The disease caused by the co-infection with both Lyme disease and babesiosis was shown decades ago to be more severe in experimental animals(15). This observation has now been extended to human co-infections. Krause and colleagues reported that 11% of patients with Lyme disease in southern New England are co-infected with babesiosis(7). Co-infected patients had significantly more fatigue, headache, sweats, chills, anorexia, emotional lability, nausea, conjunctivitis, and splenomegaly than those with Lyme disease alone. Furthermore, 50% of these patients were ill for >= 3 months compared to 7% with Lyme disease. This increase in the number and duration of symptoms may be attributed to immunosuppression associated with babesial infection(7,15).

    Recently, immunoserologic evidence of co-infection with a third tick-transmitted bacterial zoonosis, Ehrlichia species (HGE and HME), has been reported(12,16,17). In a sero-epidemiologic study of residents of Wisconsin and Minnesota, 9.4% of patients with Lyme disease had serologic evidence of co-infection: 5.2% with HGE, 2.1% with babesiosis, and 2.1% with both(16). Similarly in Sonoma County, California, 23% of residents were seroreactive to antigens from one or more tick-borne agents: 1.4% to Lyme, 0.4% to HGE, 4.6% to HME, and 17.8% to babesia-like piroplasm WA-1(12). These studies indicate that tick-borne diseases are widespread and prevalent in some regions of the United States. Travelers from Canada will be at risk when they visit these areas during tick season (generally from May to September in the northeast). Furthermore, I. scapularis ticks have been identified in approximately 250 locations in Canada(8). Prolonged parasitemias that may accompany co-infection with babesiosis, or subclinical infection in Canadian travelers who acquire any of the tick-borne pathogens, may facilitate transmission of infection to I. scapularis ticks in regions of Canada where they reside(7). Finally, blood products are not routinely screened for B. microti or B. burgdorferi. Babesiosis may be transmitted by blood transfusion and is a cause of febrile transfusion reactions in endemic areas(18,19).

    In summary, malaria should always be considered in febrile travelers and in cases of fever of unknown origin, even in those without a travel history(20). But clinicians should also consider babesiosis in the differential diagnosis of febrile travelers returning from enzootic areas of the United States where, during the tick season (May to September), infection with B. microti and B. burgdorferi is not uncommon. Furthermore, we suggest that all patients with a documented tick-transmitted infection be evaluated for co-infection with other known tick-borne agents, particularly if symptoms are severe or persist after therapy. Given the current levels of travel between Canada and the United States, and the emergence of Lyme disease, babesiosis, and ehrlichiosis, we must anticipate an increase in the number of imported cases of these tick-borne pathogens in Canadians. Prompt recognition of cases, accurate identification, and appropriate initial management is crucial in reducing morbidity and mortality associated with these infections.


    1. White DJ, Chang HG, Benach JL et al. The geographic spread and temporal increase of the Lyme disease epidemic. JAMA 1991;266:1230-36.
    2. Daniels TJ, Falco RC, Schwartz I et al. Deer ticks (Ixodes scapularis) and the agents of Lyme disease and human granulocytic ehrlichiosis in a New York City park. Emerging Infect Dis 1997;3:353-55.
    3. Benach JL, Coleman JL, Habicht GS et al. Serologic evidence for simultaneous occurrences of Lyme disease and babesiosis. J Infect Dis 1985;152:473-78.
    4. Grunwaldt E, Barbour AG, Benach JL. Simultaneous occurrence of babesiosis and Lyme disease. N Engl J Med 1983;308:1166.
    5. Marcus LC, Steere AC, Duray PH et al. Fatal pericarditis in a patient with coexistent Lyme disease and babesiosis: demonstration of spirochetes in the myocardium. Ann Intern Med 1985:103:374-76.
    6. Golightly LM, Hirschorn LR, Weller PF. Fever and headache in a splenectomized woman. Rev Infect Dis 1989;11:629-37.
    7. Krause PJ, Telford III SR, Spielman A et al. Concurrent Lyme disease and babesiosis: evidence for increased severity and duration of illness. JAMA 1996;275:1657-60.
    8. ProMED. Lyme Disease - Canada. URL: <>. Date of access: 23 Aug. 1997.
    9. Sumner JW, Nicholson WL, Massung RF. PCR amplification and comparison of nucleotide sequences from the groESL heat shock operon of Ehrlichia species. J Clin Microbiol 1997;35:2087-92.
    10. Loutan L, Rossier J, Zufferey G et al. Imported babesiosis diagnosed as malaria. Lancet 1993;342:749.
    11. Quick RE, Herwaldt BL, Thomford JW et al. Babesiosis in Washington state: a new species of Babesia? Ann Intern Med 1993:119:284-90.
    12. Fritz CL, Kjemtrup AM, Conrad PA et al. Seroepidemiology of emerging tickborne infectious diseases in a northern California community. J Infect Dis 1997;175:1432-39.
    13. Spach DH, Liles WC, Campbell GL et al. Tick-borne diseases in the United States. N Engl J Med 1993;329:936-47.
    14. Benezra D, Brown AE, Polsky B et al. Babesiosis and infection with human immunodeficiency virus. Ann Intern Med 1987;107:944.
    15. Purvis AC. Immunodepression in Babesia microti infections. Parasitology 1977;75:197-205.
    16. Mitchell PD, Reed KD, Hofkes JM. Immunoserologic evidence of co-infection with Borrelia burgdorferi, Babesia microti, and human granulocytic Ehrlichia species in residents of Wisconsin and Minnesota. J Clin Microbiol 1996;34:724-27.
    17. Magnarelli LA, Dumler S, Anderson JF et al. Coexistence of antibodies to tick-borne pathogens of babesiosis, ehrlichiosis, and Lyme borreliosis in human sera. J Clin Microbiol 1995;33:3054-57.
    18. Mintz ED, Anderson JF, Cable RG et al. Transfusion-transmitted babesiosis: a case from an endemic area. Transfusion 1991;31:365-68.
    19. Herwaldt BL, Kjemtrup AM, Conrad PA et al. Transfusion-transmitted babesiosis in Washington State: first reported case caused by a WA-1 type parasite. J Infect Dis 1997;175:1259-62.
    20. Baqi M, Gamble K, Keystone JS et al. Malaria: probably locally acquired in Toronto, Ontario. Can J Infect Dis. In press.

    Source: C dos Santos, MD, K Kain, MD, Tropical Disease Unit, The Toronto Hospital and University of Toronto, Toronto, ON.
  4. Mikie

    Mikie Moderator

    Just giving this a bump.

    Love, Mikie
  5. Jeanne-in-Canada

    Jeanne-in-Canada New Member

    we know most of us have concurrent stealth infections. Several on here have both the tic borne co-infections discussed in these articles. I'd guess somewhere near half of us have lyme as just one piece of the microbrial load that makes us so sick.

    I'm pretty sure I have Lyme, but I also have 2 mycoplasms and a pesky systemic candida problem (though I'm gaining on it lately). If I was ever to prove for sure I had Lyme, I would not throw out the dx of FM because I believe chronic long term Lyme never functions alone, causing what is seen as the chronic fatigue and fibromyalgia SYNDROMES.

  6. Mikie

    Mikie Moderator

    I have to agree about FMS being another valid diagnosis. I have both CFIDS and FMS. Many have Lupus or MS with FMS. If the FMS shows up after the other illness, some docs call it secondary FMS.

    Many of us have more than one condition. I believe that makes us sicker and makes our illnesses more difficult to treat.

    Love, Mikie
  7. Jeanne-in-Canada

    Jeanne-in-Canada New Member

    alms for the Lyme junkies, anyone? I'll try and find one that is more layperson friendly when I have more steam.


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