Epidemiology^[2][3]

• Epidemic typhus fever mainly occurs in cooler regions of Africa, South America and Asia. During the 1990s, there were outbreaks in Burundi, Russia and Peru. Outbreaks occur where poverty, homelessness, close human contact and lack of opportunity for washing and laundry co-exist, favouring the person-to-person spread of the human body louse. Tick-associated reservoirs of R. prowazekii have been described in Ethiopia, Mexico and Brazil.
• Sylvatic typhus (due to R. prowazekii) is found in the USA and associated with bites from the fleas of a flying squirrel.^[4]
• The incubation period of epidemic typhus is 10-14 days.
• Recrudescent typhus (Brill-Zinsser disease) occurs when latent infection reactivates and is found in about 15% of cases (even where previously treated). It may trigger new epidemics through infection of a new generation of lice.
• Endemic or murine typhus is a milder form of disease compared to epidemic typhus. It occurs globally - in temperate climates usually during the summer months and, in tropical countries, throughout the year. Active foci of endemic typhus are known in the Andes' regions of South America and in Burundi and Ethiopia.
• There is an appreciable incidence of murine typhus in parts of southern Europe. For example, 83 cases of murine typhus were documented in the city of Chania, on the island of Crete, over a five-year period from 1993–1997.^[5]

Presentation^[2][3]

• R. prowazekii vasculitis:
  • Prodromal malaise lasting 1-3 days before abrupt onset of severe headache and fever(39-40°C).
  • There may be myalgia (sufferers may adopt a crouching posture), photophobia and neurological abnormalities (seizures, confusion, drowsiness, coma and hearing loss).
  • Initially, a non-confluent, erythematous, blanching rash commencing centrally (axilla, trunk) and spreading centrifugally to the extremities (this pattern is the opposite of rashes associated with the spotted fever group of rickettsial infections). The rash does not involve the face, palms and soles and there are no eschars.
  • The rash becomes petechial and unblanching within 1–2 days of appearing. Purpura occur in a third of patients.
  • Cough, wheeze, nausea and abdominal pain are common.
  • Severe vascular compromise may cause peripheral gangrene and necrosis.
  • Recrudescent typhus (Brill-Zinsser disease) is clinically milder than the epidemic form.
• R. typhi (murine typhus):
  • Maculopapular or petechial rash in 80% fair-skinned and 20% dark-skinned people.
  • Nausea and vomiting in approximately half of cases.
  • Abdominal pain and diarrhoea in around a quarter.
  • Cough in about a third.
  • A small proportion suffer confusion, stupor and hallucinations.
  • Approximately 10% of those admitted to hospital have acute renal failure, respiratory failure or severe neurological disorders including seizures.

Differential diagnosis

• Malaria
• Dengue fever
• Typhoid
• Meningococcal disease
• Infectious mononucleosis
• Leptospirosis
• Rubella
• Measles
• Idiopathic/autoimmune vasculitis
• RMSF
• Anthrax
• Kawasaki disease
• Ehrlichiosis
• Relapsing fever
• Syphilis
• Toxic shock syndrome
• Tularaemia

Investigations^[2][3]

• Diagnosis is usually made clinically on the basis of characteristic onset and progression of illness.
• Investigations are used mainly to confirm clinical suspicions and to assess severity.
• Where the condition is suspected then antimicrobial therapy should be given whilst waiting for confirmatory serological tests, which can take up to a week to complete.
• FBC can show leucopenia ± thrombocytopenia, but WCC can be elevated or normal; atypical lymphocytes may be seen in blood film.
• U & E may reveal hyponatraemia or raised creatinine/urea.
• LFTs may show mild elevation of transaminases and low albumin levels.
• Prothrombin time is usually normal.
• Serology shows rising IgM titre in acute infection and rising IgG titre in recrudescent disease.
• Polymerase chain reaction (PCR) amplification and analysis of rickettsial DNA from serum or skin biopsy specimens can be used to diagnose the condition.
• Complement fixation (CF) test may be used to detect the specific rickettsial organism causing the illness, via detection of specific antibodies.

Associated diseases

Rickettsial (and closely-related) infections may cause several other disease entities such as:

• RMSF (USA)
• Mediterranean spotted fever (boutonneuse fever – Europe, Africa and elsewhere)
• Ehrlichiosis
• Q-fever
• Bartonellosis

Management

• When the disease is suspected, then treatment with moderate- to high-dose oral doxycycline or tetracycline should be initiated as soon as possible, usually before serological confirmation of the diagnosis. Most patients improve dramatically within 48 hours of starting treatment.
• Give antibiotics for five days or for 2-4 days after fever has subsided.
• An alternative strategy in outbreak situations (which appeared effective in the Burundi epidemic) is to give patients a single 200 mg dose of doxycycline, although there may be a higher risk of relapse with this approach.
• Chloramphenicol is also effective against rickettsiae.
• In patients with severe, acute disease, management on a high-dependency area with support measures may be needed.
• Recrudescent cases will usually be cured by a single further course of antibiotics.

Complications

• End organ damage (affecting the central nervous, musculoskeletal, cardiovascular, pulmonary and renal systems and the skin)
• Hypovolaemia
• Electrolyte disturbance
• Peripheral gangrene
• Secondary infections may occur, particularly bacterial pneumonia

Prognosis^[2]

• Uncomplicated cases that are promptly diagnosed and treated do very well and usually make a full recovery.
• Complicated or delayed cases have a higher risk of complications but still do well on the whole, dependent on comorbidity and degree of immunity from previous infections.
• Before the advent of antibiotics, mortality for epidemic typhus was as high as 60%. Indeed Ricketts (after whom the genus Rickettsia is named) died of typhus after exposure during his laboratory work. It is now thought to be between 3-4% if correct treatment is given - deaths still occur due to delayed diagnosis. Murine typhus has a mortality rate of between 1-4%.
• The highest mortality is seen in the elderly and malnourished.

Prevention^[2][3]

• Avoidance of endemic areas and crowding.
• Weekly doses of doxycycline in those entering endemic areas.
• Long-sleeved shirts and long trousers should be worn in endemic areas and changed regularly with attention to good personal hygiene.
• Infested clothing should be exposed to 70°C for >1 hr.
• Where water and fuel are in short supply, insecticides may be used to treat clothing, eg 0.5% permethrin; one treatment is sufficient unless reinfestation is expected. Treating clothing with diluted permethrin gives protection for 6 weeks.
• An alternative is to remove and leave infested clothing unworn for a week (body lice can only survive five days if deprived of blood).
• Complete eradication of epidemic typhus may be impossible because of the lifelong nature of infection with R. prowazekii and risk of reactivation.
• Control of populations of rats and other biting-arthropod bearing animals can reduce the overall incidence of endemic typhus.
• An inactivated vaccine offering partial protection against R. prowazekii has been available in the past but is not currently recommended. DNA vaccines are now under development.