Typhus

A group of febrile illnesses caused by Rickettsia species, transmitted by arthropod vectors.

They are classified into epidemic (louse borne) typhus caused by Rickettsia prowazekii, endemic (murine, flea borne) typhus caused by Rickettsia typhi, and scrub typhus caused by Orientia tsutsugamushi (transmitted by trombiculid mite larvae, or chiggers).

Each form carries a distinct epidemiological distribution and vector. They share broadly overlapping clinical features and a common, highly effective treatment approach with doxycycline.

Prompt empirical treatment on clinical suspicion is therefore appropriate, given the potential for significant morbidity and mortality if treatment is delayed pending confirmatory serological testing.

Pathophysiology and epidemiology

• Rickettsial organisms are obligate intracellular bacteria with a particular tropism for vascular endothelial cells. Infection produces a systemic vasculitis that underlies the characteristic features of fever, rash and, in severe disease, multi organ involvement.
• Severe disease reflects widespread microvascular injury and increased vascular permeability.
• Epidemic typhus is transmitted by the human body louse. It occurs classically in overcrowding, poor sanitation and cold weather, which favour louse infestation, and is historically associated with war, famine and refugee situations.
• Humans are the primary reservoir of epidemic typhus. Louse to louse transmission maintains circulation within affected populations.
• Endemic typhus is transmitted by the rat flea and occurs worldwide, with rats and other small mammals as the reservoir. It generally produces milder disease than the epidemic form.
• Scrub typhus is transmitted by chigger mites, whose larval stage feeds on rodents and, incidentally, humans. It is endemic across a broad region of the Asia Pacific.
• A characteristic eschar at the site of chigger attachment is an important diagnostic clue where present.

• Fever, headache (often severe) and myalgia characterise the typical onset across all forms. They develop after an incubation period of one to two weeks.
• A maculopapular or petechial rash is characteristic, though not universally present. It typically appears several days after fever onset and often begins on the trunk before spreading.
• This pattern is notably different from the centripetal spread typical of Rocky Mountain spotted fever, a related but geographically and vector distinct rickettsial illness.
• Scrub typhus is frequently accompanied by a characteristic eschar (a painless, black, necrotic lesion with surrounding erythema) at the site of chigger bite, with regional lymphadenopathy.
• The eschar is a valuable diagnostic clue when identified. Its absence does not exclude the diagnosis, given the variable sensitivity of this finding.
• Severe disease is more characteristic of epidemic typhus, though it occurs across all forms in a proportion of cases. It presents with progressive multi organ involvement, including altered consciousness, renal impairment, respiratory failure (from vasculitis related pulmonary involvement), and myocarditis.
• Reflecting the underlying vasculitic process, peripheral gangrene occurs in the most severe epidemic typhus presentations.
• Actively seek a relevant exposure history, given the differing epidemiological associations of each form. Relevant exposures are:
  • Travel to or residence in an endemic region.
  • Recent outdoor activity in rural or scrub vegetation areas (particularly relevant for scrub typhus).
  • Overcrowding and poor sanitation with potential body louse exposure (relevant for epidemic typhus).

• Diagnosis is frequently presumptive, based on the characteristic clinical picture and relevant epidemiological exposure. Start empirical treatment promptly, given the risk of significant morbidity and mortality with delay. Do not withhold treatment pending confirmatory testing.
• Serological testing (indirect immunofluorescence assay, the reference standard for confirmation) typically requires paired acute and convalescent samples to show a significant rise in antibody titre.
• A single early sample may therefore be negative or inconclusive. This limits its utility for immediate diagnostic decisions in the acute presentation.
• Polymerase chain reaction testing on blood, eschar swab or tissue biopsy offers more rapid diagnostic confirmation where available. It is particularly valuable in the acute phase, before a reliable antibody response has developed.
• An eschar swab, where an eschar is present, is a particularly useful and relatively non invasive sampling site for scrub typhus specifically.
• Full blood count frequently shows thrombocytopenia and, in more severe disease, evidence of disseminated intravascular coagulation.
• Liver function tests are frequently mildly to moderately deranged, reflecting the systemic nature of the underlying vasculitic disease process.

• Doxycycline 100 mg orally or intravenously twice daily for seven days is first line treatment across all forms of typhus. Continue treatment for a minimum of two to three days after defervescence.
• Doxycycline is the treatment of choice even in children. It is also the treatment of choice in pregnancy, following careful risk benefit discussion given the generally short treatment course required. The risk of severe or fatal disease if treatment is withheld or delayed pending alternatives is substantial.
• Start empirical treatment promptly on clinical suspicion in the appropriate epidemiological context. Do not wait for serological confirmation. Response to doxycycline is excellent when started early, and treatment delay risks significant morbidity and mortality.
• This is particularly relevant for epidemic typhus, given its historically high case fatality rate in untreated disease.
• Chloramphenicol is an alternative, historically used particularly where doxycycline was considered relatively contraindicated. Doxycycline is now generally preferred as first line even in these contexts, given accumulating evidence of its safety and superior efficacy across patient populations including children and pregnant women.
• Azithromycin is an alternative. It is particularly relevant for scrub typhus in regions with reported doxycycline treatment failure or relative resistance. It is also a reasonable option where doxycycline is genuinely contraindicated or not tolerated.
• Provide supportive care for complications of severe disease: renal support for acute kidney injury, respiratory support for pulmonary involvement, and correction of coagulopathy. Deliver it at a level of care appropriate to severity.
• Severe epidemic typhus in particular requires intensive supportive management, given its historically high associated mortality.
• Prevention measures are specific to the transmission route of each form:
  • Epidemic typhus: delousing measures (including treatment of clothing and close contacts) and improved sanitation and living conditions to reduce body louse infestation.
  • Endemic typhus: rodent and flea control.
  • Scrub typhus: protective clothing together with insect repellent in endemic scrub or grassland areas.
• No currently widely available effective vaccine exists for any form of typhus.