VECTOR-BORNE AND ZOONOTIC DISEASES

Volume 8, Number 1, 2008

Rickettsia amblyommii Infecting Amblyomma americanum Larvae

ELLEN Y. STROMDAHL, 1MARY A. VINCE,1PEGGY M. BILLINGSLEY,2

NICOLE A. DOBBS,3 and PHILLIP C. WILLIAMSON2

ABSTRACT

Polymerase chain reaction analysis of Amblyomma americanumadults, nymphs, and larvae from Aberdeen Proving Ground, MD (APG), revealed a very high prevalence of a spotted fever group (SFG) rickettsia. Restriction fragment length polymorphism (RFLP) and sequence analysis identified “Rickettsia amblyommii.”

This organism is not yet described or well studied, and its pathogenicity is unknown; however, investigations of the organism are warranted because of its high prevalence in A. americanum. This tick is extremely abundant at military training facilities in the south, central, and Mid-Atlantic United States, and many soldiers experience multiple concurrent tick bites.

Bites by R. amblyommii-infected A. americanummay account for rates of SFG rickettsia seropositivity

that are higher than reported rates of Rocky Mountain spotted fever (RMSF) cases from the same location. Seroconversion to SFG rickettsia following bites of A. americanummay suggest that R. amblyommii is infectious in humans. Subclinical infection in the numerous A. americanumtick bite victims could contaminate donated blood and compromise immunodeficient recipients.

Detection of R. amblyommiiin questing A. americanumlarvae suggests transovarial transmission. The absence of R. rickettsii, the agent of RMSF, in A. americanummay be due to transovarial interference by R. amblyommii. The likelihood of pathogen transmission by larvae is magnified by their habit of mass attack.

The very small size of the larvae is also a risk factor for pathogen transmission. High R. amblyommii prevalence in populations of A. americanumpresage co-infection with other A. americanum-borne pathogens.

A. americanumnymphs and adults from APG were found to be co-infected with R. amblyommii and Borrelia lonestari, Ehrlichia chaffeensisand Ehrlichia ewingii, respectively, and larval pools were infected with both R. amblyommiiand B. lonestari.

Co-infections can compound effects and complicate diagnosis of tick-borne disease.

Key words: Rickettsia amblyommii—Amblyomma americanum—Prevalence—Pathogenicity—Co-infection.

Address reprint requests to:

Ellen Stromdahl

Entomological Science Program

U.S. Army Center for Health Promotion &

Preventive Medicine

5158 Blackhawk Rd.

BLDG E-5800

Aberdeen Proving Ground, MD 21010-5403

E-mail: ellen.stromdahl@us.army.mil

RMSF vs. Lyme

Rocky Mountain Spotted Fever & Lyme

According to the CDC

Two potentially fatal infections treated differently?

According to CDC, Rocky Mountain Spotted Fever (RMSF) was responsible for 19 deaths between 2004 and 2007. In contrast, CDC reported Lyme disease was responsible for 26 deaths during the same time period.

The national incidence rate for RMSF (1997-2002) was 2.2 cases per million persons; incidence rates for Lyme disease (2009) was reported as 12.71. There were 38,468 cases of Lyme disease reported by the CDC in 2009 and 1,815 cases of Rocky Mountain Spotted Fever during that same year.

In spite of the higher number of deaths from Lyme disease, a six times higher incident rate over the tick borne RMSF, and an additional 37,000 plus more reported cases of Lyme over RMSF, only RMSF is said by the CDC to be “life-threatening”, and a “cause [of] severe illness and death”.

This same warning is not offered to those seeking information on Lyme disease. Neither is the RMSF related statement, “early empiric antibiotic therapy can prevent severe morbidity and death”, shared with the public on the CDC website in regards to Lyme disease.

In fact, the CDC casually states Lyme disease “is diagnosed based on symptoms, physical findings (e.g., rash), and the possibility of exposure to infected ticks; laboratory testing is helpful if used correctly and performed with validated methods. Typical symptoms include fever, headache, fatigue, and a characteristic skin rash called erythema migrans.”

CDC warns readers about specific difficulties regarding RMSF - “Early signs and symptoms of these illnesses are notoriously nonspecific or mimic benign viral illnesses, making diagnosis difficult.” In contrast, although Lyme disease has been referred to across the globe as “a multisystem disease” and is known as the '”great imitator” due to diversity of its clinical manifestations, the CDC has no similar warning of the difficulty with diagnosing Lyme disease on its website.

The CDC website gives the impression diagnosing Lyme early is not a priority, discourages the use of testing until weeks after possible exposure and indicates testing is not even necessary in the event a person exhibits “typical” symptoms -“Laboratory blood tests are helpful if used correctly and performed with validated methods. Laboratory tests are not recommended for patients who do not have symptoms typical of Lyme disease.” Describing Lyme disease symptoms as “typical” is a misnomer, as presentations can be varied, certain stages and symptoms may never appear, and one or more symptoms can wax and wane throughout the course of the illness, including after what is reported to be adequate treatment.

CDC states- “For example, even in areas where awareness of RMSF is high, approximately 60%--75% of patients with this TBRD receive an alternate diagnosis on their first visit for medical care (8,9).” This may be accurate, however, it is important to note that Lyme disease patients often receive multiple incorrect diagnoses, even after visiting several physicians, and the correct diagnosis is often not discovered until years after the original exposure to infected ticks, if at all.

The results of a 2009 CALDA survey, which included 2,424 Lyme patients whose clinical diagnosis was supported by positive test results, was reported at the IOM Workshop. The study determined- “More than half of patients saw 7 or more physicians to obtain a diagnosis; over a third saw 10 or more physicians. Nearly half of these Lyme patients had traveled over 50 miles to receive healthcare; 30% had traveled more than 100 miles; and 9% had traveled over 500 miles. (Travel distances of 30 miles or more are considered to impose a high healthcare access burden on a patient.) Roughly 40% had sought services at their local hospital, and approximately 82% of these Lyme patients had difficulty obtaining care.”

Additionally, the CALDA study revealed 95% of respondents had suffered with Lyme disease for more than 2 years.

The CDC warns, regarding RMSF- “The lack of a specific initial syndrome, however, does not imply that the course of these diseases will be benign.” It does not alert the public to the fact that people exposed to Lyme disease may experience the same situation.

The negative, chronic health effects from RMSF are also mentioned in detail- “Long-term health effects persisting for >1 year after acute RMSF infection include partial paralysis of the lower extremities; gangrene requiring amputation of fingers, toes, arms, or legs; hearing loss; blindness; loss of bowel or bladder control; movement disorders; and speech disorders (79).”

The literature concerning Lyme disease does not include the fact it can also cause blindness; partial paralysis of the lower extremities; hearing loss; loss of bowel or bladder control; movement disorders; or speech disorders. It also additional fails to mention many mild to severe symptoms documented in the scientific literature, such as:

Musculoskeletal disorders

Facial and dental pain- “clinical manifestations may include facial and dental pain, facial nerve palsy, headache, temporomandibular joint pain, and masticpain.” (1) Laryngoscope, 101(6 Pt 1):592-5. 1991.

Headaches- “Our patients show that headache can be the first, and for a long time the only, prominent sign of Lyme

neuroborreliosis” Headache resembling tension-type headache as the single manifestation of Lyme

neuroborreliosis. Brinck T; Hansen K; Olesen J. Cephalalgia, 13(3):207-9. 1993

...“headaches resembling migraine... tension-type headache” (3) Headache characteristics in hospitalized patients with Lyme disease. Scelsa SN; Lipton RB; Sander H; Herskovitz S. Headache, 35(3):125-30. 1995.

TMJ Pain- “Fourteen patients demonstrated temporomandibular joint pain. temporomandibular joint

disorder (TMJ) Otolaryngologic aspects of Lyme disease. Moscatello AL; Worden DL; Nadelman RB; Wormser G; Lucente F. Laryngoscope, 101(6 Pt 1):592-5. 1991.

Tongue Paresthesia- “he developed paresthesia in his tongue” [A patient with neuroborreliosis presenting gadolinium-enhanced MRI lesions in bilateral facial nerves.] Tokunaga H; Ohyagi Y; Furuya H; Araki T; Yamada T; Isogai E; Kira J. Rinsho Shinkeigaku, 41(9):632-4. 2001.

Facial Swelling- Otolaryngologic aspects of Lyme disease. Moscatello AL; Worden DL; Nadelman RB; Wormser G; Lucente F. Laryngoscope, 101(6 Pt 1):592-5. 1991.

Difficulty Swallowing- “Dysphagia” (1) Otolaryngologic aspects of Lyme disease. Moscatello AL; Worden DL; Nadelman RB; Wormser G; Lucente F. Laryngoscope, 101(6 Pt 1):592-5. 1991.

Twitching of facial or other muscles - “the other [patient] has had intermittent facial twitches for eight

months. [post treatment]” Isolation of Borrelia burgdorferi from the blood of seven patients with Lyme disease.

Nadelman RB; Pavia CS; Magnarelle LA; Wormser GP. American Journal of Medicine, 88:21-6. 1990.

Vocal Paralysis- Paralysis of recurrent laryngeal nerve in Lyme disease. Schroeter V; Belz GG; Blenk H.

Lancet, 2(8622):1245. 1988.

Hypersensitivity to noise- “Lyme disease-induced hyperacusis can be an intensely disabling, chronic condition that is accompanied by posttraumatic stress disorder-like psychobehavioral sequelae. Carbamazepine in the treatment of Lyme disease-induced hyperacusis." Nields JA; Fallon BA; Jastreboff PJ. J Neuropsychiatry Clin Neurosci, 11(1):97-9. 1999.

Pain in Ears- Otolaryngologic aspects of Lyme disease. Moscatello AL; Worden DL; Nadelman RB; Wormser G; Lucente F. Laryngoscope, 101(6 Pt 1):592-5. 1991.

“...it should be emphasized that marked variation is possible in the clinical expression of the disease. Even without treatment, some patients have very mild disease... At the opposite end of the spectrum, an occasional patient will have severe involvement of the skin, nerves, heart, and joints at the same time.” Steere AC; Malawista SE; et al. The clinical spectrum and treatment of Lyme disease. Yale Journal of Biology and Medicine 1984;57(4):453-64.

“Clinically, this borrelial infection is most like syphilis in its multisystem involvement, occurrence in stages, and mimicry of other diseases. ...Lyme disease’s great range of presentations can make recognition difficult.” Steere AC. Lyme disease. New England Journal of Medicine 1989;321:586-596.

“Symptoms can be surprisingly variable, so that days of near normality can alternate with days of profound debility.”

Pachner AR. Early disseminated Lyme disease. American Journal of Medicine 1995;98 (suppl):4A-30S-43S.

“As in other spirochetoses, such as syphilis, the symptoms may be fulminant, with a sudden onset, or may develop insidiously over many years. The variable clinical manifestations have led to an awareness of this disorder as a “great imitator” that must be considered in the differential diagnosis of numerous complaints, especially in those geographic areas where the spirochete is endemic.” Cooke WD; Dattwyler RJ. Complications of Lyme borreliosis. Annual Review of Medicine 1992;43:93-103.

“Lyme disease has now been shown to involve nearly every organ and organ system in both sexes.”

Duray PH. Clinical pathologic correlations of Lyme disease. Rev Infect Dis 1989;Vol 11(Suppl. 6):S1487-S1493.

“In syphilis, ...staging is particularly useful because it is likely that the pathophysiology of stage 2 and stage 3 disease differs; this is far less clear with neuroborreliosis. Considerable data suggest that the differences between early and late neuroborreliosis are more quantitative than qualitative, with the different syndromes representing different points on a continuum, all with the same pathophysiologic mechanism. Moreover, the clinical phenomena in neuroborreliosis often do not follow an obligatory temporal sequence; any symptoms may develop without an antecedent stage 1 illness. For example, arthritis (generally considered stage 3 disease) may occur

early, on occasion even preceding EM; meningitis (nominally stage 2) may develop after arthritis, and so on. All this suggests that dividing neuroborreliosis into early versus late phenomena, while occasionally reassuring to the physician and patient, may lack pathophysiologic validity.” Halperin JJ. Neuroborreliosis. Am J Med 1995;Vol 98(4A):52S-56S.

“This pattern of persistent infection, acute disease, disease remission, and intermittent bouts of exacerbation is typical of untreated human Lyme disease.” Barthold SW; de Souza MS; Janotka JL; Smith AL; Persing DH. Chronic Lyme borreliosis in the laboratory mouse. Am J Path 1993;143(3):959-71.

“The syphilis spirochete can live in the CNS for long periods, as evidenced by the fact that patients with general paresis usually do not manifest neurologic symptoms until 15 years after infection. A lengthy latency within the CNS also appears to exist in Lyme disease, with neurologic symptoms not becoming manifest for months or even years.” Pachner AR. Neurologic manifestations of Lyme disease, the new “Great Imitator.” Rev Inf Dis 1989;Vol. 11(Suppl 6):S1482-6.

Fatigue- “often constant and may be incapacitating”. The clinical spectrum and treatment of Lyme disease.

Steere AC; Malawista SE; Bartenhagen NH; Spieler PN; Newman JH; Rahn DW; et al. Yale Journal of Biology and Medicine, 57(4):453-64. 1984.

Lyme from CDC site- “There is some evidence that PTLDS is caused by an autoimmune response, in which a person's immune system continues to respond, doing damage to the body’s tissues, even after the infection has been cleared.”

Also on CDC site- “As with many infectious diseases, there is no test that can "prove" cure.”

In comparison, the CDC website reports:

“Tickborne rickettsial diseases (TBRD) continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low cost, effective antimicrobial therapy.”

RMSF- “…greatest challenge to clinicians is diagnosing these infections early in their clinical course, when antibiotic therapy is most effective.”

“…understand that early empiric antibiotic therapy can prevent severe morbidity and death.”

“Early signs and symptoms of these illnesses are notoriously nonspecific or mimic benign viral illnesses, making diagnosis difficult.”

“Early signs and symptoms of these illnesses are notoriously nonspecific, or they might mimic benign viral illnesses, making diagnosis difficult. For example, even in areas where awareness of RMSF is high, approximately 60%--75% of patients with this TBRD receive an alternate diagnosis on their first visit for medical care (8,9).”

“The lack of a specific initial syndrome, however, does not imply that the course of these diseases will be benign.”

“Two recent cross-sectional studies in the southeastern and south central United States* have indicated that up to 22% of children have serologic evidence of previous exposure to antigens of both E. chaffeensis (15) and R. rickettsii (16), suggesting that rickettsial and ehrlichial infection might be more common than previously recognized.”

“Long-term health effects persisting for >1 year after acute RMSF infection include partial paralysis of the lower extremities; gangrene requiring amputation of fingers, toes, arms, or legs; hearing loss; blindness; loss of bowel or bladder control; movement disorders; and speech disorders (79).”

“Similarly, HME and HGA can cause serious or fatal disease as well, although at lower rates than are observed for RMSF.”

“Approximately 3% of HME patients and less than 1% of HGA patients with symptoms severe enough to seek medical attention will die from the infection (25,34,47).”

“In addition, advanced patient age and delay in diagnosis and the onset of specific antibiotic therapy are predictors of a more severe course of HGA (53).”

“TBRD can be life-threatening.”

“TBRD can be life-threatening. Severe manifestations of TBRD include prolonged fever, renal failure, myocarditis, meningoencephalitis, hypotension, acute respiratory distress syndrome, and multiple organ failure. Patients usually do not have diagnostic serum antibody levels during the first week of illness; therefore, an inability to detect antibodies (IgG or IgM) in acute-phase serum does not exclude TBRD.

RMSF- “Health-care providers should not delay treatment while waiting for a diagnosis; rather, they should empirically provide treatment if they suspect TBRD. Doxycycline is the drug of choice for the treatment of presumptive or confirmed TBRD in both adults and children.” … “Several laboratory methods are available to diagnose TBRD. However, they vary in the time required to obtain results and in the type of information they provide the clinician. Therefore, treatment decisions should be based on epidemiologic and clinical clues and should never be delayed while waiting for laboratory confirmation of a diagnosis. “

Lyme- “Several weeks after infection, currently available ELISA, EIA and IFA tests and two-tier testing have very good sensitivity.” “Just as it is important to correctly diagnose Lyme disease when a patient has it, it is important to avoid misdiagnosis and treatment of Lyme disease when the true cause of the illness is something else.”

Lyme- “Lyme disease is diagnosed based on symptoms, physical findings (e.g., rash), and the possibility of exposure to infected ticks; laboratory testing is helpful if used correctly and performed with validated methods.”

Lyme- “You may have heard that the blood test for Lyme disease is correctly positive only 65% of the time or less. This is misleading information. As with serologic tests for other infectious diseases, the accuracy of the test depends upon the stage of disease. During the first few weeks of infection, such as when a patient has an erythema migrans rash, the test is expected to be negative.

“Long-term health effects persisting for >1 year after acute RMSF infection include partial paralysis of the lower extremities; gangrene requiring amputation of fingers, toes, arms, or legs; hearing loss; blindness; loss of bowel or bladder control; movement disorders; and speech disorders (79).”

Lyme- Lingering symptoms after treatment (post-treatment Lyme disease syndrome)

Approximately 10-20% of patients with Lyme disease have symptoms that last months to years after treatment with antibiotics5. These symptoms can include muscle and joint pains, cognitive defects, sleep disturbance, or fatigue. The cause of these symptoms is not known, but there is no evidence that these symptoms are due to ongoing infection with B. burgdorferi. This condition is referred to as Post-treatment Lyme disease syndrome (PTLDS).

Last Updated- April 2019

Lucy Barnes

AfterTheBite@gmail.com