Borrelia hermsii final

The exciting life of

Borrelia hermsii

A Case Study!

• September 7th, 2006: 51-year-old man cleans room associated with a 100-year-old solar telescope at Mt. Wilson Observatory, located at 1,737 m (5,700 feet) elevation in San Gabriel mountains. Floor was littered with rodent feces, acorn husks, and other debris suggesting years of rodent occupation.

• September 9th, 2006: Carried old boxes with rodent nests. Some material transferred to clothing. Noticed 2 “insect bites” on each leg just above sock line.

• September 17th, 2006: Experienced sudden onset of weakness, fever, shaking chills, muscle and joint pain.

• September 18th, 2006: Nausea and vomiting developed. • September 20th, 2006: Sought help at a clinic, prescribed antiemetics. No

improvement. • September 21st, 2006: Presented at hospital emergency department. Physical

indicated fever and dehydration. CBC showed mild thrombocytopenia and increased granulocyte count. Treated with ketorolac, metoclopramide, and intravenous saline for possible viral illness and was released. Improved over the next several days.

Case study cont.

• September 27th, 2006: Relapsed with increased weakness, arthralgia, and myalgias, fever, shaking chills and nausea and vomiting.

• September 28th, 2006: Illness peaked. • September 29th, 2006: Illness improved. • October 1st, 2006: Relapsed. Returned to emergency room and was

hospitalized. High fever, and treated with intravenous fluids, antiemetics, and piperacillin/tazobactam. CBC showed leukocytosis, left shift and thrombocytopenia. Routine blood cultures (which do not support Borrelia growth) were negative. Improved after a few hours of receiving antimicrobial drug treatment and was mildly hypotensive for a day.

• October 3rd, 2006: Drug treatment discontinued. Patient was released. Night sweats continued for 2 days after discharge and felt generalized weakness for the next several days.

• October 16th, 2006: Patient returned to full time work.

Presenter

Presentation Notes

Because of a suspicion that the patient had contracted tick-borne relapsing fever, the exposure site was investigated for ticks. A member of the research team designed a novel tick trap in which a white terry cloth towel was wrapped around small blocks of dry ice, which emits CO2 and attracts ticks. In late October 2006, the traps collected 6 ticks, which were sent to the Rocky Mountain Laboratories, where they were identified as O. hermsi nymphs and tested for spirochete infection.

Disease Presentation • Tick-borne relapsing fever (TBRF) is characterized by

recurring febrile episodes. Each febrile episode ends with a sequence of symptoms collectively known as a "crisis”.

• This phase is followed by the "flush phase", characterized by drenching sweats and a rapid decrease in body temperature. Patients may become transiently hypotensive.

• Patients who are not treated will experience 1 to 4 episodes of fever before illness resolves.

Presenter

Presentation Notes

Febrile episodes that last ~3 days and are separated by afebrile periods of ~7 days Each febrile episode ends with a sequence of symptoms collectively known as a "crisis." During the "chill phase" of the crisis (10-30 minutes duration), patients develop very high fever (up to 106.7°F or 41.5°C) and may become delirious, agitated, tachycardic and tachypneic.

Identifying Characteristics • Typical laboratory results of TBRF patients include: 1. Normal to increased white blood cell count with a left shift towards immature cells 2. Mildly increased serum bilirubin level 3. Mild to moderate thrombocytopenia 4. Elevated erthrocyte sedimentation rate 5. lightly prolonged prothrombin time (PT) and partial thromboplastin time (PTT) • Patients typically appear moderately ill and may be

dehydrated. Occasionally a macular rash or scattered petechiae may be present on the trunk and extremities.

Diversity and Distribution • First observed in California, USA, in 1921 when

2 persons were infected in a cabin in Nevada County, north of Lake Tahoe.

• Most persons who became ill had exposures at high elevations in various mountain locations.

• Later found to be endemic near Big Bear Lake in the San Bernardino Mountains, San Bernardino County, in southern California.

• The primary cause of tick-borne relapsing fever in western North America and responsible for most cases in the United States is Borrelia hermsii.

Presenter

Presentation Notes

Borrelia hermsii is a rodent-associated spirochete transmitted by the fast-feeding soft tick Ornithodoros hermsi, which prefers coniferous forests at altitudes of 1,500 and 8,000 feet where it feeds on tree squirrels and chipmunks. Though, in a recent Montana outbreak, they found O. hermsi and dead American robin chicks (Turdus migratorius) in nest material from the cabin’s attic. Possible bird role. This tick has been found in southern British Columbia, Washington, Idaho, Oregon, California, Nevada, Colorado, and the northern regions of Arizona and New Mexico

Map from http://www.cdc.gov/relapsing-fever/distribution/

Presenter

Presentation Notes

Most TBRF cases occur in the summer months when more people vacationing and sleeping in rodent-infested cabins. But, TBRF can also occur in the winter months. Fires started to warm a cabin are sufficient to activate ticks resting in the walls and woodwork. During the years 1990-2011, 483 cases of TBRF were reported in the western U.S., with infections being transmitted most frequently in California, Washington, and Colorado.

Transmission: The vector • Borrelia bacteria that cause TBRF are transmitted to humans through the bite of

infected "soft ticks" of the genus Ornithodoros. • Humans come into contact with soft ticks by sleeping in rodent-infested cabins.

The ticks emerge at night and feed briefly on humans while they sleep. Bites are painless, most people unaware. Humans are “accidental” alternative host.

• There are several Borrelia species that cause TBRF, and these are usually associated with specific species of ticks.

• Ornithodoros hermsi tends to be found at higher altitudes (1500 to 8000 feet) where it is associated primarily with ground or tree squirrels and chipmunks.

• Soft ticks can live up to 10 years; in certain parts of the Russia the same tick has been found to live almost 20 years!

Presenter

Presentation Notes

In most cases, borreliae must rely on an insect vector to transmit the organisms through the epidermis. Soft ticks differ in two important ways from the more familiar "hard ticks" (e.g., the dog tick and the deer tick). 1. bite of soft ticks is brief, usually lasting less than half an hour. 2. soft ticks do not search for prey in tall grass or brush. Instead, they live within rodent burrows, feeding as needed on the rodent as it sleeps. ticks emerge at night and feed briefly while the person is sleeping. The bites are painless, and most people are unaware that they have been bitten. Between meals, the ticks may return to the nesting materials in their host burrows. There are several Borrelia species that cause TBRF, and these are usually associated with specific species of ticks. For instance, B. hermsii is transmitted by O. hermsi ticks, B. parkerii by O. parkeri ticks, and B. turicatae by O. turicata ticks. Each tick species has a preferred habitat and preferred set of hosts. Soft ticks can live up to 10 years; in certain parts of the Russia the same tick has been found to live almost 20 years. Individual ticks will take many blood meals during each stage of their life cycle, and some species can pass the infection along through their eggs to their offspring. The long life span of soft ticks means that once a cabin or homestead is infested, it may remain infested unless steps are taken to find and remove the rodent nest.

Transmission: The organism

Borreliae is able to undergo multiple cyclic antigenic variations, which results in the relapses of the patients

0.2 to 0.5 μm by 4 to 18 μm Seven to twenty periplasmic flagella originate at each end and overlap at the center of the cell.

Presenter

Presentation Notes

The mechanisms by which they reach the bloodstream are unknown. The relapses are due to the ability of borreliae to undergo multiple cyclic antigenic variations. At least 24 different serotypes were detected in populations of Borrelia hermsii that originated from a single organism. These serotypes were identified by staining with specific fluoresceinated antisera prepared against cloned populations of living organisms of each type. Type 7 is the most dominant. Each of the 24 types were shown to change to 7 or more other serotypes. Spirochetemia in mice was persistent, and relapses occurred when the concentration of organisms was sufficient for detection by visual means. After mice were inoculated with a single organism, peak spirochetemia usually occurred on day 4, after which clearance of organisms occurred, and what was apparently pure population was replaced by a mixed population consisting of as many as seven variants. These types persisted for 2-3 d before being replaced by other types. Conversions occurred constantly and were independent of relapses. Spontaneous conversion was clearly demonstrated in tubes of fortified Kelly's medium inoculated with a single organism of type 7 or 21. As antibodies for the predominant antigenic type multiplying within the host appear, these organisms “disappear” from the peripheral blood and are replaced by a different antigenic variant within a few days. This process may occur several times in an untreated host, depending on the infecting Borrelia strain. The ticks usually become infected by feeding on borrelemic rodents. In contrast to the louse, all tissues of the tick are invaded, resulting in transovarial transmission and the presence of borreliae in salivary and coxal (basal segment of appendage) secretions. These spirochetes in the salivary and coxal secretions enter the host through the bite wound while the tick is feeding (less than 1 minute may be required for transmission).

Isolation Methods

• Blood samples obtained before antibiotic treatment can be cultured using: 1. BSK (Barbour Stoner Kelly) medium 2. By inoculating immature mice

• B. hermsii requires higher amount of serum in the media.

• Microaerophillic • Microscopy is the test of choice for

diagnosis of relapsing fever

Presenter

Presentation Notes

Glucose, amino acids, long-chain fatty acids, N-acetylglucosamine, and several vitamins are some of their required organic nutrients. The borreliae are microaerophilic organisms. Borrelia hermsii has a generation time of 12 hours when cultivated in artificial media at 35°C compared with only 6 to 10 hours in the mouse.

Laboratory Diagnosis

• Diagnosis made by detecting spirochetes in a thin and thick smear of peripheral blood prepared with Wright’s or Giemsa stain or by culture isolation.

• Best visualized by dark field microscopy, but the organisms can also be detected using Wright-Giemsa or acridine orange stains.

• They do not Gram stain well. • Organism is best detected from blood cultures

when the patient is febrile. • Serology not useful for immediate diagnosis and

may have cross reactions with B. burdorgferi.

Presenter

Presentation Notes

With subsequent febrile episodes, the number of circulating spirochetes decreases, making it harder to detect spirochetes on a peripheral blood smear. Even during the initial episode spirochetes will only be seen 70% of the time. Borrelia spp. are susceptible to drying, hypotonic or hypertonic conditions, dilute detergents, and temperatures above 40ºC

Gram Stain

Borrelia is a flexible spirilla spirochete with internal flagella

Presenter

Presentation Notes

Members of the genus Borrelia stain poorly with the Gram stain reagents and are considered neither gram-positive nor gram-negative, even though they have an outer membrane similar to gram-negative bacteria and may be called Gram- in the literature.

Wright-Giemsa Stain

Borrelia hermsii MTW-2 in mouse blood viewed at 600× oil immersion. Scale bar = 40 μm.

Presenter

Presentation Notes

Aniline dyes such as Wright-Giemsa are better for visualizing Borrelia spp.

Treatment and Sequelae • TBRF spirochetes are susceptible to penicillin and

other beta-lactam antimicrobials, as well as tetracyclines, macrolides, and potentially fluoroquinolones. CDC has not developed specific treatment guidelines for TBRF.

• With appropriate treatment, most patients recover within a few days. Long-term sequelae rare but include iritis, uveitis, cranial nerve and other neuropathies.

• TBRF contracted during pregnancy can cause spontaneous abortion, premature birth, and neonatal death.

• The maternal-fetal transmission of Borrelia is thought to occur either transplacentally or while traversing the birth canal.

Presenter

Presentation Notes

Although not a nationally notifiable condition, prompt reporting of TBRF cases is currently required in at least 12 states, California being one of them. Regardless of location, health care providers should report cases to appropriate state or local health authorities. Large multistate outbreaks have been linked to rental cabins near national parks and other common vacation locations, and prompt reporting by clinicians was critical to the identification and control of these outbreaks. Without corrective action, tick-infested cabins can remain a source of human infection for many years.

Please, laugh a little…

Disease caused by Borrelia hermsii although few, but the impact of the infections can be long and mortality is estimated around 5-10% if untreated. Prevention includes: 1. Avoid sleeping in rodent

infested buildings 2. Rodent proof structures

to prevent colonization of rodents and their soft ticks.

References Photo Credits • http://wwwnc.cdc.gov/eid/article/9/9/03-0280-f1.htm • http://wwwnc.cdc.gov/eid/article/15/7/09-0223-f2.htm • http://www.cdc.gov/relapsing-fever/transmission/ • http://jem.rupress.org/content/156/5/1297.full.pdf Case study • http://wwwnc.cdc.gov/eid/article/15/7/09-0223_article.htm Information • https://www.inkling.com/read/medical-microbiology-murray-rosenthal-pfaller-

7th/chapter-39/borrelia • http://www.cdc.gov/relapsing-fever/clinicians/ • http://www.ncbi.nlm.nih.gov/books/NBK8451/ • http://www.aafp.org/afp/2005/1115/p2039.html • http://www.uptodate.com/contents/clinical-features-diagnosis-and-

management-of-relapsing-fever • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725891/ • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC356836/ • http://jem.rupress.org/content/156/5/1297

http://wwwnc.cdc.gov/eid/article/9/9/03-0280-f1.htm

http://wwwnc.cdc.gov/eid/article/15/7/09-0223-f2.htm

http://www.cdc.gov/relapsing-fever/transmission/

http://jem.rupress.org/content/156/5/1297.full.pdf

http://wwwnc.cdc.gov/eid/article/15/7/09-0223_article.htm

https://www.inkling.com/read/medical-microbiology-murray-rosenthal-pfaller-7th/chapter-39/borrelia

https://www.inkling.com/read/medical-microbiology-murray-rosenthal-pfaller-7th/chapter-39/borrelia

http://www.cdc.gov/relapsing-fever/clinicians/

http://www.ncbi.nlm.nih.gov/books/NBK8451/

http://www.aafp.org/afp/2005/1115/p2039.html

http://www.uptodate.com/contents/clinical-features-diagnosis-and-management-of-relapsing-fever

http://www.uptodate.com/contents/clinical-features-diagnosis-and-management-of-relapsing-fever

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725891/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC356836/

http://jem.rupress.org/content/156/5/1297

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Borrelia hermsii final