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Synonyms: Relapsing fever borreliosis, louse-borne relapsing fever (LBRF, also known as epidemic relapsing fever), tick-borne relapsing fever (TBRF, also known as endemic relapsing fever).
Relapsing fever is an umbrella term used to describe characteristic patterns of infection caused by spirochetes of the genus Borrelia. It owes its name to the classical presentation of a fever that spontaneously remits and relapses, helping, historically, to distinguish it from other infectious diseases that caused fever. It can be classified into two broad categories dependent upon the vector that transmits it to people and thus the particular species causing the infection:
- Louse-borne relapsing fever (LBRF or epidemic relapsing fever):
- Vectors – human lice of body and head – Pediculus humanus or P. capitis, but not the pubic louse, P. pubis
- Infective agent is B. recurrentis
- Tends to cause the severest form of the disease
- Man is primary host and reservoir (there is no transovarial transmission of the infecting organism to the progeny of the human lice)
- Infection is transmitted direct from louse haemolymph after crushing the organism through scratching or via conjunctivae/broken skin (organism does not infect salivary or other glands of lice)
- Rarely, person-to-person transmission can occur through blood-to-blood contact, eg needle-stick injury
- Causes epidemic outbreaks of illness when public-health maintenance breaks down, eg during wars, famine, conditions of widespread poverty, displacement and overcrowding (estimated 10 million people affected during/after World War II).
- Tick-borne relapsing fever (TBRF or endemic relapsing fever):
- Vectors – soft-bodied ticks of the genus Ornithodoros that often (but not always) share their species name with the species of borrelia that they transmit, eg Ornithodoros turicatae carries B. turicatae and similarly so for B. hermsii and B. parkeri
- Not so for B. duttonii, B. hispanica, and B. persica – there are at least 15 infecting species of borrelia and a similar number of transmitting ticks around the world
- Tends to cause a less severe/acute form of the disease
- Small mammals and lizards are hosts, ticks being the reservoir, passing borrelia on transovarially to their progeny
- Borrelia do infect the salivary glands of the ticks and so transmission occurs quickly (minutes) during tick-feeding (in contrast to the hard-bodied tick-borne diseases, eg Lyme disease – caused by B. burgdorferi – where the process takes many hours)
- The illness occurs mainly in rural communities where people are in close proximity to small mammals that carry the soft-bodied ticks, in a chronic endemic pattern.
The incidence and prevalence of the diseases is very hard to estimate as they often go unrecognised or are misdiagnosed in the current era of easily available antibiotics. Endemic relapsing fever is only encountered in the very southernmost regions of Europe (particularly Mediterranean Spain and Asia Minor), but has an appreciable presence throughout the rest of the world's continents, with the exception of Australasia. On the whole, endemic relapsing fever is unheard of in Britain and rare throughout Europe, except in travellers returning from areas where it is encountered. Clusters of cases can occur in groups of returning travellers who camp in rural settings where the disease is endemic. Currently, epidemic relapsing fever is found only in Ethiopia and neighbouring countries, although its occurrence among homeless people of industrialised European cities has been suspected but not confirmed.
After exposure to an infected louse or tick, spirochetes enter the dermis and gain access to the bloodstream where they infect the endothelium. The organism then rapidly disseminates to spleen, liver, lungs, kidneys, central nervous system and bone marrow. Spirochetaemia leads to a low-grade disseminated intravascular coagulation and thrombocytopenia. It is thought that visceral and neurological manifestations may be due to vascular microemboli rosetting around individual spirochete organisms.
Borrelia organisms display genetically programmed variation in the proteins in their cell membrane, known as variable major proteins or VMP. The VMP mechanism allows the organism to avoid the effect of antibodies directed against them and explains the relapsing nature of the illness; they succumb to, then evade, antibodies that attack them and give the characteristic pattern of illness. During episodes of fever there is marked spirochetaemia. During remitting periods of the illness the organisms can still be found in certain organs, particularly the bone marrow and central nervous system.
Children and women appear to be more severely affected and have a more intense disease course than adult males. The incubation period ranges from about 4–14 days. There is an acute onset of high fever, chills, arthralgia, myalgia, constitutional upset, headaches and a dry cough. Other features include:
- Scattered petechiae on the trunk and limbs
- Iritis and iridocyclitis
- Neurological symptoms and signs
- Hepatomegaly ± splenomegaly
- Gastrointestinal symptoms including abdominal pain, nausea, vomiting and diarrhoea
- Spontaneous abortion in pregnant sufferers
The primary illness usually lats for about 3 days, then after a fever-free period of about 7 days there will be multiple alternating episodes of illness, usually shorter and milder than the original episode. The initial illness can end in a severe crisis that may precipitate fatal bacteraemic shock. There tends to be 1–2 relapses in the epidemic form and 3–4 in the endemic form.
There is a wide differential diagnosis depending upon the phase of the illness and the conditions and geographical location in which the sufferer picked up the problem. The following diagnoses should be considered, taking into account the travel history and the setting in which the illness was contracted:
- Dengue fever
- Haemorrhagic fevers
- Viral hepatitis
- Infectious mononucleosis
- Leptospirosis (Weil's disease)
- Rickettsial infections, particularly louse-borne typhus and Rocky Mountain Spotted Fever
- Rat bite fever (streptobacillary fever)
- Colorado tick fever
- Trench fever
- Idiopathic or autoimmune vasculitis
- Kawasaki's disease
- Toxic shock syndrome
- WCC is usually normal, platelets may be low, and prothrombin time/activated partial thromboplastin time is prolonged.
- LFTs will often show elevation of the transaminases.
- Elevation of urea and creatinine can occur in louse-borne relapsing fever.
- During active illness, thick and thin blood films should be repeatedly viewed to demonstrate spirochetaemia using dark-field microscopy or conventional microscopy with Giemsa, Wright's or DIff-Quick® staining; thick-films are about 20 X as sensitive as thin films in picking up the disease.
- Analysis of bone marrow aspirate and CSF during the acute phase of the illness may also demonstrate the presence of spirochetes.
- Quantitative buffy coat fluorescence analysis has also been described as a very sensitive and specific technique for detecting borrelia in blood.
- Injection of the patient's serum into mice/other animals and examination of their blood is a way of making the diagnosis in the absence of laboratory services and historically was a very useful test.
- Molecular polymerase chain reaction analyses are increasingly being used as an experimental and clinical tool to allow diagnosis and species differentiation.
- Tetracyclines are very effective against all the relapsing-fever-causative organisms.
- Tetracycline 500 mg 3–4 times daily for 5–10 days, or doxycycline 100 mg twice daily for a similar period are currently thought to be the optimal regimens.
- Penicillin, erythromycin, chloramphenicol or ceftriaxone are also thought to be effective.
- The Jarisch-Herxheimer reaction has been reported during treatment of this condition (particularly when using penicillin).
- Jarisch-Herxheimer reaction during treatment
- Neurological sequelae due to microemboli
- Jaundice due to hepatitis
- Bleeding diathesis due to disseminated intravascular coagulation (potentially fatal in brain/GI tract)
- Death during acute severe bacteraemia due to septic shock (particularly epidemic relapsing fever)
If diagnosed and treated early in its course then the mortality for endemic relapsing fever is low at around 1% or less. Epidemic relapsing fever tends to carry a higher mortality of around 5% or so, even if treated. Untreated, epidemic relapsing fever traditionally carries a mortality of 30–40%, with endemic relapsing fever being less severe and causing significantly fewer deaths.
- For louse-borne infection:
- Good personal hygiene and attention to sanitation in areas of overcrowding
- Chemical control of the louse vector may help to reduce the risk of infection and spread
- Prevention of war, famine and forced mass migration helps stop the conditions in which the disease thrives from arising.
- For tick-borne disease:
- Avoidance of geographical areas where the illness is known to be endemic
- Precautions when in these areas, such as not camping in woodland may be helpful
- Long-sleeved light-coloured clothing increases the chance that ticks will be noticed and removed before feeding
- Rodent-control measures and the use of insecticides can reduce the prevalence of the disease in endemic areas
- Post-exposure treatment with doxycycline in those who suspect they have been bitten by ticks has been shown to be effective.
Further reading and references
; Tick-Borne Disease Am Fam Phys 2005
; Epidemiology of relapsing fever borreliosis in Europe. FEMS Immunol Med Microbiol. 2006 Oct48(1):11-5.
; Relapsing Fever. eMedicine, January 2007 Overview from emergency department perspective.
; Relapsing Fever. eMedicine, December 2006 Overview from infectious diseases viewpoint.
; Characteristics of louse-borne relapsing fever in Ethiopian children and adults. Ann Trop Med Parasitol. 2004 Mar98(2):191-6.
; Postexposure treatment with doxycycline for the prevention of tick-borne relapsing fever. N Engl J Med. 2006 Jul 13355(2):148-55.
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