Lymphoreticular and Hematopoetic Infections
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RELAPSING FEVER


General Goal: To know the cause(s) of this disease, the most common modes of transmission, and the major manifestations of this disease.

Specific Educational Objectives: The student should be able to:

1. recite the common means of transmission and identify the major disease manifestations.

2. realize this another one of those diseases that has recurrent fevers. Be able to distinguish this recurring fever from the others.

3. recite the diseases that when treated result in a Jarisch-Herxheimer reaction.

Reading: MEDICAL MICROBIOLOGY by P.R. Murray, K.S. Rosenthal, and M.A. Pfaller, 6th Edition. pp. 411-416.

Lecture: Dr. Neal R. Chamberlain

References: eMedicine Online: Tick Borne Diseases, Relapsing Fever. (http://www.emedicine.com/emerg/topic590.htm; Last accessed 2/25/10)

Overview

Relapsing fever is a recurring febrile disease transmitted to humans by ticks (endemic form) and by body lice (epidemic form). It is caused by several different Borrelia species.

Etiology

Endemic relapsing fever is caused by at least 15 different Borrelia species. Soft ticks of the genus Ornithodorus spread the tick-borne variety. The Borrelia species that cause endemic relapsing fever are named according to the species name of the tick that transmits the bacterium to humans; for example, Borrelia parkeri is transmitted by Ornithodoros parkeri, and Borrelia hermsii is transmitted by Ornithodoros hermsii.

Epidemic relapsing fever is caused by Borrelia recurrentis but has not caused a human infection in over 80 years. It will not be discussed in this handout.

Manifestations

In endemic relapsing fever, an abrupt onset of symptoms is usually seen with high fever, rigors, severe headache, muscle pains, weakness, anorexia, weight loss, and cough. Systemic complications can include nausea, vomiting, upper abdominal pain due to liver and spleen involvement, and a dry cough. Other manifestations include splenomegaly, hepatomegaly, jaundice, rash, respiratory symptoms, and central nervous system involvement.

A primary febrile episode ends within 3 to 6 days and can culminate in fatal shock. Patients who survive will appear well for about 7 to 10 days; after a period of no manifestations of fever, the fever will relapse and last from 3 to 6 days. Subsequent relapses tend to be less severe. There are from 3 to 10 relapses seen in most cases of endemic relapsing fever.

Epidemiology

Pathogenesis

In endemic relapsing fever, soft ticks feed for short periods during the night and then fall off the host. A patient can be infected with Borrelia within minutes after the tick attaches to the host. This is an important distinction from other tick-borne diseases, such as Lyme disease, in that the ticks feed for longer periods of time and it can take several hours before Borrelia burgdorferi cells infect the human host.

Large numbers of Borrelia are present in the bloodstream (spirochetemia) following transmission from the tick. During the spirochetemia, Borrelia invades the endothelium. After multiplying in the endothelial cells, the bacteria are released into the bloodstream and patients develop symptoms that include fever. Symptoms resolve when the host’s immune system produces antibodies to the proteins on the outer surface of the Borrelia and eliminates the bacteria from the bloodstream. However, Borrelia that remains in the endothelial cells are not killed and can change the proteins on their outer surface. Borrelia producing new outer membrane proteins can avoid destruction by antibodies directed against the original infecting bacteria. Thus, the patient clinically improves until the Borrelia, with different surface proteins, multiplies sufficiently to cause another relapse. This period of bacterial multiplication can take from 7 to 10 days. Specific immunoglobulin-complement–mediated lysis and the release of endotoxin accounts for some of the symptoms. Relapses continue until the Borrelia no longer produce novel antigenic variations of their surface proteins. If untreated, most organs of the body are infected; mortality is usually associated with myocarditis.

Diagnosis

The signs and symptoms of relapsing fever can be very similar to those of typhoid fever. However, in relapsing fever, the patient’s pulse rate is rapid in proportion to the fever. A relative bradycardia occurs in typhoid fever and helps to differentiate relapsing fever from typhoid fever. Relapsing fever can be mistaken for brucellosis or malaria; however, the periodicity of the fevers is different (Table Endo-1). A peripheral blood smear stained with Giemsa or Wright stain will demonstrate the spirochetemia in 70% of patients during the febrile period and results in a definitive diagnosis.

Table Endo-1. Some Diseases with Recurring Fevers: Causative Agent, Periodicity of Fever, and Length of Fever

Disease

Causative Agent

Periodicity of Fever

Length of Fever

Malaria

Plasmodium

Every 2–3 days (except P falciparum where fever can be continuous)

Fever lasts 24 hours, with the fever ending in a drenching sweat

Brucellosis

Brucella

Every day

Fever recurs in the evening and is gone by morning, with the fever ending in a drenching sweat

Relapsing fever

Borrelia

Every 7–10 days

Fever lasts 7–10 days

Therapy and Prevention

The mortality rate of endemic relapsing fever is 1% with treatment, and 30–70% without treatment. Tetracycline is effective in the treatment of relapsing fever. As was seen in the treatment of syphilis, patients treated for relapsing fever may also experience a Jarisch-Herxheimer reaction. This reaction produces apprehension, diaphoresis, fever, tachycardia, and tachypnea, with an initial pressor response followed rapidly by hypotension. Erythromycin or chloramphenicol can be used in the treatment of pregnant women and children. It should be noted that chloramphenicol can cause serious and sometimes fatal blood dyscrasias (e.g., aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) and should only be used in seriously ill children.

To prevent endemic relapsing fever, it is important to wear proper clothing that keeps ticks from gaining access to the skin and apply N,N-diethyl-m-toluamide (DEET)  in tick-laden areas; cabins in endemic regions should be treated with insecticide; and rodents should be controlled for endemic disease.

Send comments and email to Dr. Neal R. Chamberlain, nchamberlain@atsu.edu
Revised 2/25/10
©2010 Neal R. Chamberlain, Ph.D., All rights reserved.