Relapsing fever pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Roghayeh Marandi keywords: VMP:Variable membrane proteins

Overview

Borrelia is usually transmitted via the tick bite or body louse to the human host. After entering the bloodstream, spirochetes replicate extracellularly and remain predominantly in the plasma space. Patients generally remain asymptomatic until high-level spirochetemia (104-108 organisms m!) develops, at which time symptoms begin abruptly. Organisms are cleared predominantly by opsonizing antibodies with the resolution of symptoms ( afebrile period), followed several days or weeks later by the reemergence of a new antigenic strain, high-level spirochetemia, and recurrence of symptoms. There are multiple genes in the spirochete encoding variable membrane proteins( VMPs). These VMPs determine the antigenic serotype of the organism. At any given time, each spirochete has VMP genes that are expressed and others that are silent. An antigenic switch occurs when a given VMP gene transposes from silent to an expressed locus. This cyclical process of initially effective immune response followed by antigenic variation and immunologic escape is responsible for the relapsing nature of this illness.

Pathophysiology

Cyclical process

Incubation period

Incubation period = time from tick bite to illness

  • 7 days, range 2 to 18 days

Symptomatic period

Symptomatic period= Length of illness = time from symptom onset to resolution of symptoms

  • 3 days, range 2 to 7 days
  • In LBRF, the fever usually lasts 3-6 days and is usually followed by a single, milder episode. In TRBF, multiple episodes of fever occur, and each may last up to 3 days.

Number of relapses = number of episodes of reoccurring/relapsing symptoms

  • 3 times, can occur up to 10 times in persons who are not treated. Most cases eventually resolve spontaneously.
  • Patients with louse-borne relapsing fever will typically have 1-2 relapses (range 0-6) with each subsequent relapse usually less severe than the previous one.
  • Patients with tick-borne relapsing fever usually have 3-5 relapses (range 0-22).
  • During episodes of spirochetemia, the organisms may invade the brain, eye, inner ear, heart, liver. Splenic abscesses and infarcts, and hemorrhages within the central nervous system, a perivascular histiocytic interstitial myocarditis, conduction defects, arrhythmias, and myocardial failure, splenic rupture with massive hemorrhage, cerebral hemorrhage, and hepatic failure are seen in LBRF which can result in sudden death.Hepatitis with patchy hemorrhages and necrosis, meningitis, and perisplenitis, thrombi in small vessels also are found. Thrombi are occasionally found occluding small vessels.[1]CNS involvement is more common in TBRF than LBRF, however eschars, ARDS, cranial nerve palsies, focal neurologic deficits, uveitis, iritis or iridocyclitis, splenic rupture and myocarditis may be seen in both TBRF and LBRF.[2][3]Most information on the pathophysiologic aspects of fatal cases comes from autopsy data of louse-borne disease in humans or experimental animals.[3]

CNS, Eye involvement in LBRF

Afebrile period

Afebrile period= Length of time before reoccurrence = time from the resolution of symptoms to reoccurrence of symptoms

  • 7 days, range 4 to 14 days
  • Organisms are cleared predominantly by opsonizing antibodies with the resolution of symptoms ( afebrile period), followed several days or weeks later by the reemergence of a new antigenic strain, high-level spirochetemia, when high-level spirochetemia (104-108 organisms m!) develops, at which time symptoms begin abruptly.

Crisis

  • AS mentioned before, most cases eventually resolve spontaneously. Occasionally, the crisis occurs after the resolution, which is a classic series of stages that a person will go through:
  • 1. Phase one is the chill phase, with the person experiencing high fevers up to 41.5°C (106.7°F). With this high temperature, a person can develop delirium, agitation, and confusion. In addition, other signs of an increased metabolic rate are noted, such as a fast heart rate and breathing rate. This phase lasts between 10 and 30 minutes.
  • 2. Phase two is the flush phase. This is where the body temperature decreases rapidly, and the person has drenching sweats. During this phase, the person's blood pressure can drop dramatically[4]
  • During the crisis, patients may develop cerebral edema with seizures, cardiac failure, or death. This stage may result in death in up to 10% of patients.

Immunity

  • Specific serotypes can recur within an individual. Infection with a given strain of Borrelia may cause partial protection against subsequent infection by the same strain. In some highly endemic areas, relapsing fever is more severe in newcomers than natives.

Genetics

The development of the cyclical process is the result of antigenic variation and subsequent immunologic escape:

References

  1. Warrell DA (January 2019). "Louse-borne relapsing fever (Borrelia recurrentis infection)". Epidemiol. Infect. 147: e106. doi:10.1017/S0950268819000116. PMC 6518520 Check |pmc= value (help). PMID 30869050.
  2. Blevins SM, Greenfield RA, Bronze MS (July 2008). "Blood smear analysis in babesiosis, ehrlichiosis, relapsing fever, malaria, and Chagas disease". Cleve Clin J Med. 75 (7): 521–30. doi:10.3949/ccjm.75.7.521. PMID 18646588.
  3. 3.0 3.1 Dworkin MS, Schwan TG, Anderson DE, Borchardt SM (September 2008). "Tick-borne relapsing fever". Infect. Dis. Clin. North Am. 22 (3): 449–68, viii. doi:10.1016/j.idc.2008.03.006. PMC 3725823. PMID 18755384.
  4. http://www.cdc.gov/ncidod/dvbid/RelapsingFever/RF_biology.htm http://www.cdc.gov/ncidod/dvbid/RelapsingFever/index.htmhttp://www.cdc.gov/ncidod/dvbid/RelapsingFever/RF_Symptoms.htm