Relapsing fever

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Roghayeh Marandi

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.

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 (1867–1868). 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.

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.

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.

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.

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.

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 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.

Not applicable

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 can be made by Microscopy, PCR, or serology.

The gold-standard diagnosis for relapsing fever is [[Microscopic examination|direct [[microscopic]] visualization]] of borreliae in a Giemsa-stained thick blood smears.

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 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.

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

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.

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.

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.

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.

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.

Research continues to find a vaccine against relapsing fever.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Roghayeh Marandi

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 (1867–1868). 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.

Discovery

• 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.^[1]
• Livingston first described tick-borne relapsing fever in 1857.
• The association between spirochetes and the development of louse-borne relapsing fever first described by Otto Obermeier in 1873 after an outbreak in Berlin (1867–1868).^[1]
• 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 bloodstrem.^[2]
• The role of the human body louse in the transmission of relapsing fever was reported by MacKie in 1907.^[2]

Roghayeh Marandi

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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.

There are two forms of relapsing fever:

• Endemic tick-borne or TBRF
• Epidemic louse-borne or LBRF

Tick-borne Relapsing Fever = Endemic Relapsing Fever

• Sporadic cases
• Transmitted by soft ticks

Louse-borne Relapsing Fever = Epidemic Relapsing Fever

• Transmitted person-to-person by the human body lice (vectors) from an infected human reservoir.

Template:WH Template:WS

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

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.

• Borrelia is usually transmitted via the tick bite or body louse to the human host.
• Borrelia is able to induce cycles of disease by varying antigen expression and by displaying new outer-surface proteins(VMPs) during the disease course(antigenic variation). The antigenic variation contributes to the recurring nature of relapsing fever.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.

Incubation period = time from tick bite to illness

• 7 days, range 2 to 18 days

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

• 3 days, range 2 to 7 days
• During episodes of spirochetemia and replicate extracellularly and remain predominantly the plasma space. Borrelia invades the endothelium. After multiplying in the endothelial cells, the bacteria are released into the bloodstream and patients develop symptoms that include fever. However,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]

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.

• Most cases eventually resolve spontaneously. Occasionally, the crisis occurs after the resolution. 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.

• 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.
  

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

• There are multiple genes in the spirochete encoding variable membrane proteins( VMPs) which are the outer membrane of spirochetes contains surface proteins. Attacks of relapsing fever end abruptly when specific bactericidal immunoglobulin M antibodies generated by the B1b cell subset lyse spirochaetes in the blood, independently of complement and T cells. These VMPs determine the antigenic serotype of the organism and 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 mechanism of antigenic variation presumably leads to immunologic escape and relapse. Because of the organism’s ability to undergo antigenic variation, several serotypes may be present in the bloodstream at one time.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Roghayeh Marandi

Relapsing fever is a bacterial infection caused by several species of spirochete bacteria in the Borrelia family. TBRF is caused by more the 15 Borrelia species: Borrelia hermsii, Borrelia turicatae, Borrelia parkeri, Borrelia duttonii, Borrelia johnsonii, Borrelia miyamotoi. LBRF is caused by 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 tickborne Borrelia species.

• Borrelia recurrentis causes louse-borne (epidemic) relapsing fever.
• More than 15 additional Borrelia species can cause tick-borne (endemic) relapsing fever.Tick-borne relapsing fever (TBRF) is transmitted by the Ornithodoros tick (soft body ticks) from a small mammal reservoir and occurs in Africa, Spain, Saudi Arabia, Asia, and certain areas in the western United States and Canada

Borrelia miyamotoi disease can cause tick-borne relapsing fever but is transmitted by hard ticks. (sometimes called hard tick relapsing fever)]

• Borrelia are gram-negative, helical, 8-30 11m long, 0.2-0.5 11m wide, and have 3-10 loosely coiled spirals. They are visible with light microscopy.they are flagellated and highly motile, and they divide by binary fission, with doubling times. They have a unique process of DNA rearrangement in their linear DNA. Each time the DNA is read a different antigenic marker, also known as a variable major protein, is created, which allows the organism to evade the immune system and therefore cause recurrent patterns of fever and other symptoms.

• They are difficult to cultivate on artificial media. Because of frequent antigenic variation, difficult to serotype, and also identifying of Borrelia species by standard bacteriologic methods is problematic, so the nomenclature has relied on the vector specificity of these organisms.

• 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.

Borrelia recurrentis is the only agent of louse-borne disease. Pediculus humanus, is the specific vector.

• Borrelia organisms that then multiply in the gut of the louse. When an infected louse feeds on an uninfected human, the organism gains access when the victim crushes the louse or scratches the area where the louse is feeding. B.recurrentis infects the person via mucous membranes and then invades the bloodstream.
• No animal reservoir exists
• A single louse can only infect one person, but nosocomial infections are possible from contamination by infected blood.

• More than 15 additional Borrelia species can cause tick-borne (endemic) relapsing fever, which is transmitted to humans through the bite of infected “soft ticks” of the genus Ornithodoros. Soft ticks (family Argasidae) differ in many ways from the so-called hard. Also, Borrelia species are usually associated with specific species of ticks. For example, 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. They live in the nests of squirrels, chipmunks, and other small animals like chicken & pigs. They feed very quickly(less than a half-hour) and painlessly.
• When rodents or other natural hosts vacate a cabin, humans may become the only available host. Patients usually are unaware of a tick bite or exposure.
  

The bacteria species associated with TBRF are:

• Borrelia duttoni
• Borrelia hermsii
• Borrelia parkerii.
• Relapsing infections are acquired from “Borrelia hermsii” or “Borrelia parkeri” can be spread from rodents, and serve as a reservoir for the infection, via a tick vector. “Borrelia hermsii” and “Borrelia recurrentis” cause very similar diseases, although the condition associated with “Borrelia hermsii” has more relapses and is responsible for more fatalities. In contrast, the disease caused by “B. recurrentis” has longer febrile and afebrile intervals and a more extended incubation period.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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

The following infectious diseases should be considered in someone with recurrent episodes of a febrile illness:^[1]

• Colorado tick fever
• Infectious mononucleosis
• Ascending (intermittent) 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.
• In a febrile patient in or from Africa, who has all the classic features of LBRF (jaundice, petechial rash, epistaxis, hepatosplenomegaly, thrombocytopenia, coagulopathy, and elevated serum aminotransferase), severe falciparum malaria is the most differential diagnosis.
• In the Horn of Africa, yellow fever and other viral hemorrhagic fevers such as Rift Valley Fever and viral hepatitis, rickettsial infections, especially louse-borne typhus must be considered.
• If there is evidence of acute kidney injury, leptospirosis is more likely.
• Trench fever (Bartonella Quintana), transmitted by lice, can also cause episodic recurrent fever with headache and pains in the shins. Still, it lacks the bleeding and jaundice that is seen in LBRF.

In endemic areas, complicating bacterial infections, particularly typhoid, or coinfection with malaria, should be considered.

• In refugees diagnosed in Europe, P. falciparum malaria, sepsis, leptospirosis, and meningitis have been cited as leading differential diagnosis of LBRF.^[2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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%.

• It is reported that 15 million cases of louse-borne relapsing fever (LBRF) and more than 5 million deaths occurred in Africa, Eastern Europe, and Russia in the past.

• In the early 1900s, many large epidemics were described, predominantly in Africa, the MiddleEast, India, and China. With improved hygiene, the incidence of epidemic relapsing fever has declined in the 20th century, but the disease continues to be a problem in countries of Africa, Asia, and South America.
• Only in North-Eastern Africa, especially the highlands of Ethiopia where an estimated 10,000 cases of LBRF occur annually and affect mostly homeless people living in very unhygienic and crowded conditions especially during rainy seasons. ^[1]
• Only a few cases TRBF are reported in the U.S. annually.

• The death rate for untreated LBRF ranges from 10 – 70%. In TBRF, it is 4 -10%.
• With antibiotic treatment, the mortality of epidemic relapsing fever decreases from 10% to 40% to 2% to 4%.
• Fatalities are lower in tick-borne disease compared to louse-borne disease, with treatment.^[2]

• There is no racial predilection to relapsing fever.

• TBRF is endemic in the western U.S., southern British Columbia, plateau regions of Mexico, Central and South America, the Mediterranean, Central Asia, and Africa.
• The first endemic region of TBRF in the US was identified in 1915 in Colorado (Meader 1915). However, the first case was actually in 1905 in New York in a traveler to Texas. Since then, TBRF has been reported in 14 states: Arizona, California, Colorado, Idaho, Kansas, Montana, Nevada, New Mexico, Ohio, Oklahoma, Oregon, Texas, Utah, Washington, and Wyoming.
• Most recent cases and outbreaks have occurred in a rustic cabin or vacation home settings at higher elevations (> 8,000 feet) in coniferous forests in the western U.S.
• TBRF occurs typically in summer months when people are traveling to mountainous areas on vacation. TBRF can occur in winter, mainly when people go into rodent-infested cabins and start fires, warming the place and producing carbon dioxide and warmth that attract the ticks that transmit TBRF.

• TBRF is reported worldwide, except Antarctica, Australia, and the Pacific Southwest.

Although TBRF was removed from the list of nationally notifiable conditions in 1987, 11 states require TBRF to be reported to their State Health Departments (Arizona, California, Colorado, Idaho, Nevada, New Mexico, Oregon, Texas, Utah, Washington, and Wyoming). Other states, such as Montana, may institute reporting in the future. ^[3]. Most cases of endemic relapsing fever occur in the late spring and summer.

LBRF is mainly a disease of the developing world. It is currently seen in Ethiopia and Sudan. Famine, war, and the movement and groups of refugees often result in epidemics of LBRF. The largest recent epidemics of LBRF occurred during World Wars I and II. At least 1 million people died during these epidemics.^[4] it is currently prevalent in Ethiopia and Sudan.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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.

Sleeping in caves, wood cabins, or earthen floored huts in areas

Poor personal hygiene, overcrowding like in military camps, prisons, street children sleeping areas, civilian population disrupted by war and other disasters.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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.

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.

• Most cases resolve spontaneously. but after several cycles of fever, some people may develop dramatic central nervous system signs such as seizures, stupor, and coma. Also, the Borrelia organism may also invade heart and liver tissues, causing inflammation of the heart muscle (myocarditis), endocarditis, and liver (hepatitis), pneumonia are other complications such as iridocyclitis, meningitis, encephalitis, abnormal coagulation with hemorrhage and spontaneous abortion or transplacental transmission.

TBRF in pregnancy

TBRF during pregnancy can cause spontaneous abortion, [[premature birth, and neonatal death (Melkert and Stel 1991). The maternal-fetal transmission of Borrelia is believed to occur either transplacentally (Steenbarger 1982) or while traversing the birth canal. In one study, perinatal infection with TBRF was shown to lead to lower birth weights, younger gestational age, and higher perinatal mortality.

• Given appropriate treatment, most patients recover within a few days. The death rate for untreated LBRF ranges from 10 – 70%. In TBRF, it is 4 -10%. With early treatment, the death rate is reduced.
• Poor prognostic signs include severe jaundice, severe change in mental status, severe bleeding, and prolonged QT interval on ECG.