Relapsing fever overview

# Overview
Relapsing fever is a bacterial infection caused by several species of spirochete bacteria in the Borrelia family.It is a vector-borne disease that is transmitted through louse or soft-bodied tick bites.

# Historical Perspective
Relapsing fever has been described since the days of Hippocrates in ancient Greeks. however, the term relapsing fever was first used by David Craigie to describe an outbreak of the disease in Edinburgh in 1843. Livingston first described tick-borne relapsing fever in 1857. The association between spirochetes and the development of louse-born relapsing fever first described by Otto Obermeier in 1873 after an outbreak in Berlin (18671868). Cook, Ross, Milne, Dutton, Todd, Koch, and others studied TBRF extensively throughout southern and eastern Africa in the early 1900s.In 1904, Ross and Milne, while working in Uganda, showed that TBRF was caused by a spirochete in the bloodstream. The role of the human body louse in the transmission of relapsing fever was reported by MacKie in 1907.

# Classification
There are two major forms of relapsing fever: endemic tick-borne and epidemic louse-borne. TBRF is transmitted by the soft body ticks (vectors) from a small mammal reservoir and maybe endemic or sporadic. LBRF is transmitted person-to-person by human body lice (vectors) from an infected human reservoir.

# Pathophysiology
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 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.

# Causes
Relapsing fever is a bacterial infection caused by several species of spirochete bacteria in the Borrelia family. TBRF is caused by more than 15 Borrelia species: Borrelia hermsii, Borrelia turicatae, Borrelia parkeri, Borrelia duttonii, Borrelia johnsonii, Borrelia miyamotoi. The bacteria species associated with LBRF is Borrelia recurrentis which has a genome so similar to B. duttonii and B. crocidurae (causes of East and West African tick-borne relapsing fever).Humans are the sole reservoirs of Borrelia recurrentis, while small mammals (eg, pets, ground and tree squirrels, chipmunks) and reptiles (lizards, snakes, gopher tortoises) may serve as a reservoir for tick-borne Borrelia species.

# Differentiating Relapsing fever from Other Diseases
The following infectious diseases should be considered in someone with recurrent episodes of a febrile illness:
Colorado tick fever,Infectious mononucleosis, Ascending cholangitis , Yellow fever, African hemorrhagic fevers, Lymphocytic choriomeningitis, Dengue fever, Leptospirosis, Infections with echovirus 9, Malaria, Chronic meningococcemia, Infections with Bartonella species, Brucellosis, Rat bite fever.

# Epidemiology and Demographics
TBRF is endemic in the western US, southern British Columbia, plateau regions of Mexico, Central, and South America, the Mediterranean, Central Asia, and much of Africa. In the United States. LBRF is mainly a disease of the developing world. It is currently seen in Ethiopia and Sudan. Famine, war, overcrowding, and the movement of refugee groups often result in LBRF epidemics. With antibiotic treatment, the mortality of epidemic relapsing fever decreases from 10% to 40% to 2% to 4%.

# Risk Factors
Risk factors of TBRF: Sleeping in caves, wood cabins, or earthen floored huts in areas, Risk factors of LBRF: Poor personal hygiene, overcrowding like in military camps, prisons, street children sleeping areas, civilian population disrupted by war and other disasters.

# Screening
Not applicable

# Natural History, Complications, and Prognosis
Most cases eventually resolve spontaneously. If left untreated, during the crisis up to 10% of patients with relapsing fever may progress to develop cerebral edema with seizures, cardiac failure, or death. Common complications of relapsing fever are iridocyclitis, meningitis, encephalitis, myocarditis, endocarditis, pneumonia, abnormal coagulation with hemorrhage, and spontaneous abortion or transplacental transmission. With early treatment, the death rate is reduced. Those who have developed coma, myocarditis, liver problems, or pneumonia are more likely to die.

# Diagnosis
Diagnosis can be made by Microscopy, PCR, or serology.

## Diagnostic Study of Choice
The gold-standard diagnosis for relapsing fever is ] visualization]] of borreliae in a Giemsa-stained thick blood smears.

## History and Symptoms
The symptoms of relapsing fever present 3-7 days (up to 18 days) after exposure with sudden onset of high fever, chills, headache, myalgias, and weakness. Less common symptoms include anorexia, nausea, vomiting, abdominal pain, arthralgias, neck pain or back pain, confusion, lethargy, cough, rash, sore throat, and swollen lymph nodes.If left untreated, rapid defervescence usually occurs in 2-6 days (range 1-13 days), often with dramatic improvement in symptoms. Most cases eventually resolve spontaneously.The clinical manifestations of tick-borne and louse-borne relapsing fever are similar but can be quite variable, depending on the infecting strain of Borrelia and the host's immunity.

## Physical Examination
Physical examination of patients with relapsing fever is usually remarkable for the moderately ill-appearing appearance, mild to moderately dehydration, fever, tachycardia, and hepatosplenomegaly.  Less frequently lymphadenopathy, jaundice, abdominal tenderness, pulmonary rales, skin rash, meningismus, delirium, aphasia, hemiplegia, facial paralysis, or other neurologic findings may be present.

## Laboratory Findings
The presence of spirochetes in smears of peripheral blood, bone marrow, or cerebrospinal fluid in a symptomatic person is diagnostic of relapsing fever.
The diagnosis of relapsing fever is confirmed by the identification of the borrelia in the patient's blood under microscopy. Laboratory tests may also reveal mild anemia with normal to increased leukocyte count.  Biochemistry may reveal Mildly increased serum bilirubin and  hepatic aminotransferase level, increased urea nitrogen, creatinine, Elevated ESR.
Slightly prolonged coagulation tests, PT and APTT, as well as proteinuria or hematuria, are also common

## Imaging Findings
Chest radiographs are usually clear but may show pulmonary edema or pneumonic consolidation.Ultrasound may be helpful in the diagnosis of hepatomegaly or splenomegaly associated with relapsing fever. CT scan may be helpful in the diagnosis of complications of relapsing fever, which include cerebral hemorrhage.

## Other Diagnostic Studies
Analysis of CSF is indicated if signs of meningitis or meningoencephalitis are available shows mononuclear pleocytosis, a mildly to the moderately elevated protein level, and normal glucose levels in the CSF support the diagnosis of CNS borrelia infection. ECG may be helpful in the diagnosis of complications of relapsing fever. A prolonged corrected Q-T interval on electrocardiography may be present in persons with RF-induced myocarditis.

# Treatment

## Medical Therapy
Antimicrobial therapy for relapsing fever in adults depends on the vector (Tick-borne vs. Louse-borne) and includes either doxycycline, erythromycin, or tetracyclines. intravenous ceftriaxone is added if either meningitis or encephalitis is present.

## Primary Prevention
Wearing clothing that fully covers the arms and legs outdoors, Insect repellents such as DEET on the skin and clothing also work. Rodent( reservoir)  control. Tick and lice control in high-risk areas is another important public health measure. Epidemics are controlled by sterilizing clothing to eliminate lice, using pediculicides, and by improving personal hygiene.

## Secondary Prevention
There is no commercially available vaccine for Relapsing fever, it is notable that 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.

## Cost-effective of therapy

## Future or Investigational Therapies
Research continues to find a vaccine against relapsing fever.