Typhus

Synonyms: Epidemic typhus, rickettsaemia, louse-borne typhus, classical typhus, recrudescent typhus (Brill-Zinsser disease).

This disease is notifiable in the UK under the Public Health (Infectious Diseases) Regulations 1988.

See also: Scrub typhus.

This group of acute febrile illnesses is caused by infection with Rickettsiae spp. These obligate intracellular bacteria are transmitted to man via an arthropod host. They then parasitize the endothelial cells of blood vessels causing a multisystem vasculitis.¹ The body louse (Pediculus corporis) is the usual vector. When biting and feeding on its human host, it causes itching. When the irritated area is scratched, louse faeces containing rickettsiae are inoculated into the skin and then pass into the bloodstream to cause rickettsaemia. Typhus is endemic in many parts of the world with epidemic outbreaks often associated with wars and natural disasters, or any cause of overcrowding and poverty.

• Endemic and murine typhus have a highly variable prevalence depending on geographical location and local environmental factors. There is an appreciable incidence of murine typhus in parts of southern Europe.
• There were 83 cases of murine typhus in the city of Chania, on the island of Crete, over a five-year period from 1993–97.³
• A recent serological survey of southern Spain found evidence of past infection in a representative general population of 6.5% due to R. felis and 3.8% due to R. typhi.²
• Epidemic typhus, by definition, arises in outbreaks at various sites when environmental conditions and a suitable gathering of host humans coincide.

• R. prowazekii vasculitis:
  • Intense headache, high fever and macular rash normally appearing 4–5 days after onset of illness
  • Initially central rash spreading peripherally (spotted fever group of rickettsial infections cause the opposite).
  • May be myalgia, photophobia, and neurological abnormalities
  • Rash becomes petechial and unblanching within 1–2 days of appearing.
  • Cough, wheeze, nausea and abdominal pain in ~33%
  • Delirium in nearly half of patients
  • Deafness/tinnitus is possible
  • Less commonly causes mental dullness, coma and seizures, peripheral gangrene
  • Possible mild hepatomegaly/splenomegaly ± generalised lymphadenopathy
  • 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 50% of cases
  • Abdominal pain and diarrhoea in around a quarter
  • Cough affects ~33%
  • 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.

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

• Diagnosis is usually made clinically on basis of characteristic onset and progression of illness.
• Investigations used mainly to confirm clinical suspicions and 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.
• 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.

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

• Rocky Mountain spotted fever (USA)
• Mediterranean spotted fever (Boutonneuse Fever – Europe, Africa and elsewhere)
• Ehrlichiosis
• Q-fever
• Bartonellosis

• 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.
• Give antibiotics for 7 days or until 48–72 hours after fever has resolved.¹
• 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.

• Multisystem vasculitis can cause a huge range of end organ complications 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.

• 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 co-morbidity and degree of immunity from previous infections.
• Mortality rates for epidemic and murine typhus are 3%–4% and 1%–4% respectively, since the advent of effective antibiotics.
• Untreated cases will have a mortality of around 20% in those otherwise healthy and young, and up to 60% in the ill or older population.

• 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 >1hr.
• Where water and fuel are in short supply, insecticides may be used to treat clothing, e.g. 0.5% permethrin, one treatment is sufficient unless reinfestation is expected.
• Treating clothing with diluted permethrin gives protection for 6 weeks.
• An inactivated vaccine offering partial protection against R. prowazekii is available for those spending long periods in endemic areas who would be at risk; it may reduce severity of disease in those in whom it does not prevent it.¹
• DNA vaccines are under development.
• Control of populations of rats and other biting-arthropod bearing animals can reduce the overall incidence of endemic typhus.