Typhus

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Background

Typhus refers to a group of infectious diseases that are caused by rickettsial organisms and that result in an acute febrile illness. Arthropod vectors transmit the etiologic agents to humans. The principle diseases of this group are epidemic or louse-borne typhus and its recrudescent form known as Brill-Zinsser disease, murine typhus, and scrub typhus. (For more information on pediatric scrub typhus, see the Medscape Reference article Pediatric Scrub Typhus in the Pediatric: General Medicine volume.)

Pathophysiology

Epidemic typhus is the prototypical infection of the typhus group of diseases, and the pathophysiology of this illness is representative of the entire category. The arthropod vector of epidemic typhus is the body louse (Pediculus corporis). This is the only vector of the typhus group in which humans are the usual host. Rickettsia prowazekii, which is the etiologic agent of typhus, lives in the alimentary tract of the louse. A Rickettsia- harboring louse bites a human to engage in a blood meal and causes a pruritic reaction on the host's skin. The louse defecates as it eats; when the host scratches the site, the lice are crushed, and the Rickettsia- laden excrement is inoculated into the bite wound. The Rickettsia travel to the bloodstream and rickettsemia develops.

Rickettsia parasitize the endothelial cells of the small venous, arterial, and capillary vessels. The organisms proliferate and cause endothelial cellular enlargement with resultant multiorgan vasculitis. This process may cause thrombosis, and the deposition of leukocytes, macrophages, and platelets may result in small nodules. Thrombosis of supplying blood vessels may cause gangrene of the distal portions of the extremities, nose, ear lobes, and genitalia. This vasculitic process may also result in loss of intravascular colloid with subsequent hypovolemia and decreased tissue perfusion and, possibly, organ failure. Loss of electrolytes is common.

Some people with a history of typhus may develop a recrudescent type of typhus known as Brill-Zinsser disease. After a patient with typhus is treated with antibiotics and the disease appears to be cured, Rickettsia may linger in the body tissues. Months, years, or even decades after treatment, organisms may reemerge and cause a recurrence of typhus. How the Rickettsia organisms linger silently in a person and by what mechanism recrudescence is mediated are unknown. The presentation of Brill-Zinsser disease is less severe than epidemic typhus, and the associated mortality rate is much lower. Risk factors that may predispose to recrudescent typhus include improper or incomplete antibiotic therapy and malnutrition.

Murine typhus and scrub typhus share the same pathophysiology as epidemic typhus, although they are somewhat milder. The incubation period is approximately 12 days for the typhus group. Prior infection with Rickettsia typhi provides subsequent and long-lasting immunity to reinfection.

Epidemiology

Frequency

United States

Approximately 15 documented sporadic cases of active infection with R prowazekii, the etiologic agent of epidemic typhus, have been reported. These occurred in the central and eastern portions of the United States and have been linked with exposure to flying squirrels (Glaucomys volans).[1] The flying squirrel acts as the host for R prowazekii, and transmission to humans is believed to occur via squirrel fleas or lice. Murine typhus caused by infection with Rickettsia felis is associated with opossums,[2] cats, and their fleas and occurs in southern California and southern Texas. Most cases of murine typhus in Texas occur in spring and summer, whereas, in California, the illness is most common in the summer and fall. Murine typhus is most common in adults, but infection may occur in any age group.[3] No indigenous cases of scrub typhus have occurred in the United States, although infections have been diagnosed in patients returning from endemic areas.

International

Epidemic typhus occurs in Central and South America, Africa, northern China, and certain regions of the Himalayas. Outbreaks may occur when conditions arise that favor the propagation and transmission of lice. Brill-Zinsser disease develops in approximately 15% of people with a history of primary epidemic typhus.

Murine typhus occurs in most parts of the world, particularly in subtropical and temperate coastal regions. Murine typhus occurs mainly in sporadic cases, and incidence is probably greatly underestimated in the more endemic regions. Rats, mice, and cats, which are hosts for the disease, are particularly common along coastal port regions. Populations of the flea vector may rise during the summer months in temperate climates, subsequently increasing the incidence of murine typhus. The homeless are particularly vulnerable.[4] Prior infection with R typhi provides immunity to subsequent reinfection.

Scrub typhus occurs in the western Pacific region, northern Australia, and the Indian subcontinent. The incidence of scrub typhus is largely unknown. Many cases are undiagnosed because of its nonspecific manifestations and the lack of laboratory diagnostic testing in endemic areas. However, one study found that the incidence of scrub typhus in Malaysia was approximately 3% per month, and multiple infections in the same individual are possible because of a lack of cross-immunity among the various strains of its causative organism, Orientia tsutsugamushi.[5]

Mortality/Morbidity

Epidemic typhus causes the most severe clinical presentation among the typhus group of rickettsial infections. Patients with severe epidemic typhus may develop gangrene, leading to a loss of digits, limbs, or other appendages. The vasculitic of epidemic typhus process may also lead to CNS dysfunction, ranging from dullness of mentation to coma, multiorgan system failure, and death. Untreated epidemic typhus carries a mortality rate of as low as 20% in otherwise healthy individuals and as high as 60% in elderly or debilitated persons. Since the advent of widely available antibiotic treatment, the mortality rates associated with epidemic typhus have fallen to approximately 3-4%.

The mortality rate among treated patients with murine typhus is 1-4% and less than 1% for scrub typhus.

GeoSentinel, a global network that monitors travel-related morbidity, reported no fatalities in 16 cases of murine typhus and 13 cases of scrub typhus that occurred in international travellers from 1996-2011.[6]

Sex

The typhus group of infections has no sexual predilection.

Age

The typhus group of infections has no age predilection. However, in the United States, murine typhus and sporadic cases of epidemic typhus have mainly occurred in adults.

History

Patients with typhus may have a history that includes the following:

Physical

Causes

Typhus is an acute febrile illness caused by rickettsial organisms. Rickettsia are pleomorphic bacteria that may appear as cocci or bacilli and are obligate intracellular parasites.

Laboratory Studies

Imaging Studies

Histologic Findings

Rickettsia may be observed in tissue sections using Giemsa or Gimenez staining techniques.

Medical Care

Activity

Activity is as tolerated.

Medication Summary

The goals of pharmacotherapy are to reduce morbidity, to prevent complications, and to eradicate infection.

Doxycycline (Doryx, Bio-Tab, Vibramycin)

Clinical Context:  Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. No dose adjustment is necessary in renal impairment.

Chloramphenicol (Chloromycetin)

Clinical Context:  Generally bacteriostatic to most susceptible microorganisms; binds to the 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Not preferred therapy for treating patients with typhus.

Class Summary

Specific antimicrobial therapy effective against rickettsia should be used. Doxycycline and chloramphenicol are used as antirickettsial agents for the treatment of typhus.

In Thailand, the emergence of doxycycline-resistant scrub typhus has caused clinicians to seek alternative antimicrobials.[10] Azithromycin and rifampicin have been shown to be effective in small trials conducted in areas with known doxycycline resistance.[11]

Further Inpatient Care

Further Outpatient Care

Inpatient & Outpatient Medications

Deterrence/Prevention

Complications

Prognosis

Author

Jason F Okulicz, MD, Assistant Professor of Medicine, Uniformed Services University of the Health Sciences; Staff, Infectious Disease Service, Brooke Army Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Disclosure: Nothing to disclose.

Eric A Hansen, DO, Fellow, Clinical Instructor, Department of Internal Medicine, Division of Infectious Diseases, Winthrop-University Hospital, State University of New York at Stony Brook

Disclosure: Nothing to disclose.

Mark S Rasnake, MD, FACP, Assistant Professor of Medicine, Program Director, Internal Medicine Residency, University of Tennessee Graduate School of Medicine; Consulting Staff, Department of Infectious Diseases, University of Tennessee Medical Center at Knoxville

Disclosure: Nothing to disclose.

Specialty Editors

John M Leedom, MD, Professor Emeritus of Medicine, Keck School of Medicine of the University of Southern California

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Thomas M Kerkering, MD, Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center

Disclosure: Nothing to disclose.

References

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  2. Boostrom A, Beier MS, Macaluso JA, et al. Geographic association of Rickettsia felis-infected opossums with human murine typhus, Texas. Emerg Infect Dis. Jun 2002;8(6):549-54. [View Abstract]
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  6. Jensenius M, Han PV, Schlagenhauf P, Schwartz E, Parola P, Castelli F, et al. Acute and Potentially Life-Threatening Tropical Diseases in Western Travelers--A GeoSentinel Multicenter Study, 1996-2011. Am J Trop Med Hyg. Feb 2013;88(2):397-404. [View Abstract]
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