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Facts about epidemic louse-borne typhus

Factsheet

Disclaimer: The information contained in this factsheet is intended for the purpose of general information and should not substitute individual expert advice and judgement of healthcare professionals.

Introduction

Louse-borne typhus (epidemic typhus or exanthematic typhus) is a vector-borne disease caused by Rickettsia prowazekii and transmitted through infected faeces of the body louse Pediculus humanus humanus. Louse-borne typhus is responsible for large epidemics in populations with poor sanitary and overcrowded conditions. The disease can be severe with a mortality of up to 60% without antibiotic treatment. But this can be reduced to below 5% with antibiotic and supportive treatment [1]. Sporadic cases of the relapsed form of louse-borne typhus are reported (so-called Brill–Zinsser disease). Despite the availability of treatment, louse-borne typhus is still a concern for public health authorities due its capacity to spread in vulnerable populations infested with body lice. Primary prevention of louse-borne typhus relies on measures for avoiding infestation with body lice and providing antibiotic prophylaxis in the event of an outbreak in a defined population (e.g. in refugee camps).

The pathogen

  • Louse-borne typhus is caused by Rickettsia prowazekii, an obligate intracellular gram-negative bacterium with a singular circular chromosome of 1.1 Mb.
  • R. prowazekii belongs to the typhus group of the Rickettsia genus. Rickettsia typhi, responsible for endemic typhus, also belongs to the typhus group of the Rickettsia genus but is transmitted by fleas.
  • Genomic analysis demonstrates two strains of Rickettsia prowazekii; one isolated only from humans and another identified in flying squirrels (Glaucomys volans) which is responsible only for sporadic typhus cases.

Clinical features and sequelae [1,2]

  • The incubation period of epidemic louse-borne typhus is typically between 10 and 14 days.
  • The symptoms are associated with infections of endothelial cells and the subsequent rickettsia-induced vasculitis.
  • The onset of symptoms is usually sudden after a prodromal phase of malaise lasting a few days.
  • Symptoms (relative frequency given in brackets) include high fever (100%), headache (91–100%), tachypnoea (97%), chills (82%) and muscle tenderness (70%), the latter being generally intense.
  • Rash is frequent and this clinical feature is noteworthy for supporting the diagnosis. It starts in the axillae, mostly spreads over the trunk, and may extend centrifugally towards extremities (generally sparing the face, palms and soles). Lesions initially appear as non-confluent erythematous and blanching areas, but later as petechial and even purpuric lesions, and are often attributed to vasculitis (in around one third of patients).
  • Various central neurological system symptoms can be observed (e.g. confusion, stupor, coma and seizures).
  • In addition, unspecific clinical manifestations (relative frequency given in brackets) might be associated with epidemic typhus such as abdominal pain (60%), nausea (32%), arthralgia (50%), cough (38%) and less frequently conjunctivitis. Splenomegaly may also be seen.
  • Complications of systemic vasculitis can occur with multiple organ dysfunction syndrome, and peripheral and cerebral thrombosis.
  • The case–fatality ratio can reach 60% among untreated patients, decreasing to below 5% with appropriate antibiotic treatment and supportive care.
  • Common laboratory abnormalities include thrombocytopenia, increased blood urea and increased hepatic transaminase levels.
  • Brill–Zinsser disease is a late relapse which can occur months or years after the initial R. prowazekii infection. The clinical presentation is similar to louse-borne typhus but is associated with a lower mortality rate.
  • Sporadic cases of R. prowazekii infection presumably acquired from a zoonotic origin present with symptoms comparable to louse-borne typhus.
  • Differential diagnosis includes malaria, typhoid fever, viral haemorrhagic fever, leptospirosis, endemic typhus, tick-borne and louse-borne relapsing fevers, non-typhoidal salmonellosis, meningococcal septicaemia and meningitis.

Epidemiology [1]

  • Historically, large suspected outbreaks of epidemic typhus occurred worldwide especially among military troops during the Napoleonic Wars, and first and second World Wars.
  • Epidemic typhus was widespread globally prior to the introduction of modern antibiotics. Outbreaks of louse-borne typhus occur during the colder months and have been associated with the overcrowded and unsanitary conditions that are prevalent in time of war.
  • Epidemic typhus is rarely found among travellers. It can occur in vulnerable populations where body lice are prevalent (e.g. homeless populations in impoverished areas or refugee camps).
  • Between the 1950s and 1980s, large epidemics of louse-borne typhus became less frequent and its geographical distribution has declined due to improvements in living standards. During this period, sporadic cases of plausible zoonotic origin (in the USA) and Brill–Zinsser disease were reported in the literature [3].
  • During the 1990s, louse-borne typhus re-emerged in foci associated with poor sanitary conditions (such as in prisons and refugee camps) and a colder climate found in mountainous regions. Outbreaks were reported in the rural highlands of Central and South America (especially in Peru) and Africa (Burundi, Uganda, Ethiopia, Nigeria and Rwanda) [1,4-6]. Sporadic cases or small suspected outbreaks were identified in Northern Africa, Russia and Kazakhstan, and among homeless populations in developed countries [7-11].
  • Sporadic cases of epidemic typhus from a probable zoonotic origin have been reported in several states of the eastern United States in recent decades [3,12,13].
  • Tick-associated reservoirs of R. prowazekii have been described in ticks in Ethiopia and Mexico [14,15]. The importance for human epidemiology is expected to be limited.
  • Late relapse of epidemic typhus (Brill–Zinsser disease) might be the source of a re-emerging outbreak.

Transmission

  • Rickettsia prowazekii is transmitted from human to human by the body louse Pediculus humanus humanus. The head louse (Pediculus humanus capitis) and crab louse (Phthirus pubis) can transmit R. prowazekii experimentally but known epidemics are linked to the body louse.
  • Rickettsiae may remain viable and infectious in the dead louse for weeks and in louse faeces for up to 100 days.
  • When feeding on an infected human, the body louse ingests R. prowazekii which multiplies in the epithelial cells of the midgut. When these burst, the pathogens are excreted with the faeces of the body louse. R. prowazekii has an impact on the longevity of the body louse and might kill it.
  • On average a mature body louse will live for 20–30 days. Body lice multiply rapidly and their population can increase by 11% per day.
  • Overcrowding leads to close personal contact and spread of arthropod vectors (particularly lice) among individuals. Humans become infected by contamination of the bite site with infected faeces or through contamination of the conjunctivae or mucous membranes with lice faeces. Presumed infection through aerosols of faeces-infected dust has been reported [1].
  • Rickettsia prowazekii is considered a bioterrorism agent due to specific biological features (notably with regards to environmental stability and possible aerosol transmission) [16].
  • While exposed in refugee camps and other settings characterised by crowding and poor hygiene, humanitarian relief workers and military personnel are potentially at higher risk in disease foci than the general population. In general, the risk for travellers is very low as they are applying measures that reduce exposure to body lice during travel.

Diagnostics

  • The laboratory diagnosis is based on serological tests such as indirect immunofluorescence assays and enzyme immunoassays. A four-fold increased titre of specific antibodies against R. prowazekii in acute and convalescent serum samples supports the diagnosis.
  • Serologic testing cannot stand alone as a means to confirm infection by R. prowazekii and should be interpreted in the context of the clinical presentation, immunological status of the patient and results of others supporting laboratory tests.
  • Primary infection cannot be differentiated from Brill–Zinsser disease using IgG antibody levels.
  • Culture can be used to isolate R. prowazekii from clinical samples but PCR-based genomic assays on blood and tissues can now distinguish R. prowazekii from R. typhi and other rickettsiae belonging to the spotted-fever group [17]. Particularly, quantitative real-time PCR assays have a good specificity for species identification using species-specific probe targeting the gltA gene [18].

Case management and treatment

  • Tetracycline and chloramphenicol antibiotics are highly effective therapies for epidemic typhus.
  • Early and empirical antibiotic administration should be prescribed when the diagnosis is suspected. Treatment failure within 48–72 hours is in favour of another aetiology as a patient infected with R. prowazekii should improve significantly within 48 hours of initiation of therapy [1].
  • Chloramphenicol treatment for five days (orally or intravenous) was proposed as first-line treatment in limited laboratory settings as this empirical treatment addresses other bacterial aetiologies (notably meningococcemia and typhoid fever) [1]. In outbreak situations, a single 200 mg oral dose of doxycycline has been used to limit the occurrence of relapses [1,19].
  • Supportive care can be required in patients with a severe form of epidemic typhus.

Infection control, personal protection and prevention

  • Primary prevention of louse-borne typhus relies on measures to avoid infestation with body lice.
  • Body lice are transmitted primarily by direct contact with an infested person, transmission of the body lice also occurs through fomites, like clothes or bedding.
  • Body lice are highly susceptible to cold and desiccation. They are found on clothing close to the human skin. Discarding infected clothes is an effective way to control the infestation. If this is not possible, clothes should be washed in temperature above 60 °C.
  • In outbreak situations, dusting powder with an appropriate insecticide has been applied to obtain a rapid decrease of infested persons with some lasting benefits.
  • There have been no reports of R. prowazekii transmission through substances of human origin. However, transmission via blood transfusion is theoretically possible. R. prowazekii has been experimentally transmitted to non-human primates and other animals via infected blood [20] and a case of transfusion-transmitted Rickettsia rickettsii was reported [21]. Furthermore, asymptomatic donation is possible by clinically recovered individuals with chronic persistent infection.
  • Due to possible transmission, blood collection should be avoided in refugee camps and areas where the disease is endemic. Infected individuals should be deferred from donation until signs and symptoms are gone, and a course of treatment has been completed [22]. However, in light of the chronicity of infection (i.e. Brill–Zinsser disease), a permanent deferral should be considered for infected persons without documentation of optimal therapy. Donation of cells, tissues and organs from donors deceased after typhus is not recommended. Under specific circumstances of exposure in an epidemic environment, the need for, and potential effectiveness of specific donor screening questions should be considered.

List of references

1.         Bechah Y, Capo C, Mege JL, Raoult D. Epidemic typhus. Lancet Infect Dis. 2008 Jul;8(7):417-26.
2.         Perine PL, Chandler BP, Krause DK, McCardle P, Awoke S, Habte-Gabr E, et al. A clinico-epidemiological study of epidemic typhus in Africa. Clin Infect Dis. 1992 May;14(5):1149-58.
3.         Centers for Disease Control. Epidemic typhus associated with flying squirrels--United States. MMWR Morb Mortal Wkly Rep. 1982 Oct 22;31(41):561-2.
4.         Raoult D, Birtles RJ, Montoya M, Perez E, Tissot-Dupont H, Roux V, et al. Survey of three bacterial louse-associated diseases among rural Andean communities in Peru: prevalence of epidemic typhus, trench fever, and relapsing fever. Clin Infect Dis. 1999 Aug;29(2):434-6.
5.         A large outbreak of epidemic louse-borne typhus in Burundi. Wkly Epidemiol Rec. 1997 May 23;72(21):152-3.
6.         Labruna MB. Ecology of rickettsia in South America. Ann N Y Acad Sci. 2009 May;1166:156-66.
7.         ProMED-mail. Typhus, louse-borne - Kazakhstan (north) (02). ProMED-mail 2000; 14 Jul:20000715.1168]. Available from: http://www.promedmail.org/direct.php?id=2198238. Accessed 1 October 2015.
8.         ProMED-mail. Typhus, epidemic louse-borne - Kazakhstan (north) ProMED-mail 2000; 12 Jul: 20000713.1163. Available from: http://www.promedmail.org/direct.php?id=2198233. Accessed 1 October 2015.
9.         Letaief A. Epidemiology of rickettsioses in North Africa. Ann N Y Acad Sci. 2006 Oct;1078:34-41.
10.        Badiaga S, Brouqui P. Human louse-transmitted infectious diseases. Clin Microbiol Infect. 2012 Apr;18(4):332-7.
11.        Badiaga S, Brouqui P, Raoult D. Autochthonous epidemic typhus associated with Bartonella quintana bacteremia in a homeless person. Am J Trop Med Hyg. 2005 May;72(5):638-9.
12.        Chapman AS, Swerdlow DL, Dato VM, Anderson AD, Moodie CE, Marriott C, et al. Cluster of sylvatic epidemic typhus cases associated with flying squirrels, 2004-2006. Emerg Infect Dis. 2009 Jul;15(7):1005-11.
13.        Reynolds MG, Krebs JS, Comer JA, Sumner JW, Rushton TC, Lopez CE, et al. Flying squirrel-associated typhus, United States. Emerg Infect Dis. 2003 Oct;9(10):1341-3.
14.        Medina-Sanchez A, Bouyer DH, Alcantara-Rodriguez V, Mafra C, Zavala-Castro J, Whitworth T, et al. Detection of a typhus group Rickettsia in Amblyomma ticks in the state of Nuevo Leon, Mexico. Ann N Y Acad Sci. 2005 Dec;1063:327-32.
15.        Philip CB, Lackman DB, Bell EJ, Hughes LE. Laboratory identification of typhus isolated by Reiss-Gutfreund from Ethiopian livestock ticks. Am J Trop Med Hyg. 1966 Nov;15(6):950-3.
16.        Azad AF. Pathogenic rickettsiae as bioterrorism agents. Clin Infect Dis. 2007 Jul 15;45 Suppl 1:S52-5.
17.        Zhu Y, Medina-Sanchez A, Bouyer D, Walker DH, Yu XJ. Genotyping Rickettsia prowazekii isolates. Emerg Infect Dis. 2008 Aug;14(8):1300-2.
18.        Svraka S, Rolain JM, Bechah Y, Gatabazi J, Raoult D. Rickettsia prowazekii and real-time polymerase chain reaction. Emerg Infect Dis. 2006 Mar;12(3):428-32.
19.        Perine PL, Krause DW, Awoke S, McDade JE. Single-dose doxycycline treatment of louse-borne relapsing fever and epidemic typhus. Lancet. 1974 Sep 28;2(7883):742-4.
20.        Sarycheva NI, Chirov PA. [Experimental infection of domestic animals with R. prowazeki and R. canada]. Zh Mikrobiol Epidemiol Immunobiol. 1976 Sep(9):101-4.
21.        Wells GM, Woodward TE, Fiset P, Hornick RB. Rocky mountain spotted fever caused by blood transfusion. JAMA. 1978 Jun 30;239(26):2763-5.
22.        Stramer SL, Hollinger FB, Katz LM, Kleinman S, Metzel PS, Gregory KR, et al. Emerging infectious disease agents and their potential threat to transfusion safety. Transfusion. 2009 Aug;49 Suppl 2:1S-29S.