Epidemic Typhus

Maria Salas

October 22, 2001

Epidemic Typhus

Agent: R. prowazekii

Vector: human body louse

Disease of war and poverty Plague of Athens (5th c. BC) Napoleonic Wars WWI and WWII Modern refugee camps

The Rickettsiae Gram-negative, obligate intracellular bacteria

Pleomorphic coccobacilli, ~ 2 um in length

Includes Rickettsia, Ehrlichia, Orientia, and Coxiella genera

2 antigenic groups (based on LPS) of Rickettsia species: spotted fever group (SFG) typhus group (TG)

Disease Organism Vector Reservoir

Rocky Mountain Spotted Fever

R. rickettsii Tick Ticks, wild rodents

Ehrlichiosis E. chaffeensis Ticks

Rickettsialpox R. akari Mite Mites, wild rodents

Scrub Typhus O. tsutsugamushi

Mites, wild rodents

Epidemic typhus

R. prowazekii Louse Humans, flying squirrels

Murine typhus R. typhi Flea Wild rodents

Q fever C. burnetii none Cattle, sheep, goats, cats

Pathogenesis Enter through skin -> bloodstream

Infect endothelial cells by inducing phagocytosis and escaping phagolysosome -> replicate in cytosol Can also infect m, PMNs, and fibroblasts in

vitro

R. prowazekii escapes by cell lysis

May lyse cells extracelluarly via phospholipase A production -> increased vascular permeability and hypotension

Clinical Manifestations 7-14 day incubation Fever (~ 2 weeks), chills, headache Macropapular rash after ~ 7 days,

centrifugal spread (unlike RMSF)

Myocarditis, stupor and delirium “typhos” (Greek) = smoke or haze

Clinical Manifestations Both humoral response and CMI crucial

to recovery. One attack usually confers long-lasting immunity.

There are asymptomatic carriers

Complications include vascular collapse, pneumonia, encephalitis

Mortality up to 70% in epidemics, mortality increasing with age

Brill-Zinsser Disease Recrudescent epidemic typhus

Establish latency in lymph nodes

Occurs in elderly or immunocompromised persons -> malnourishment, poverty, and war!

Milder disease (including absence of fever) and lower mortality

RESERVOIR FOR NEW TYPHUS EPIDEMICS!

Findings from sequencing the R. prowazekii genome Completed in 1998 in Sweden by

Kurland, et al. 1.1 million bp, 834 genes Toxic polysaccharides may be vaccine

targets R. prowazekii has genes similar to those

found in yeast nucleus but used by mitochondria -> mitochondrial ancestor “off-loaded” genes to host cell?

High percentage of non-functional genes in R. prowazekii

The Vector: Pediculus humanus humanus (body louse)

“It was not so long ago, indeed, that [the louse’s] prevalence extended to the highest orders of society, and was accepted as an inevitable part of existence – like baptism, or the smallpox.”

Hans ZinsserRats, Lice, and History

The Vector: Pediculus humanus humanus (body louse) Order Anoplura Life cycle (egg to egg) takes 22-28 days Eggs hatch in 5-9 days Prefers 82-86oF -> remains on human

host until death or high fever (can live 5-8 days away from host)

Prefers areas in direct contact with clothing -> neck, armpits, crotch

Lays eggs on clothing

Life cycle of body lice

Transmission Rickettsiae invade and destroy louse gut epithelial

cells

Rickettsiae released from lysed cells into gut lumen

Louse deposits rickettsiae into bite wound via infected feces

Louse dies of GI tract disease after ~2 weeks, not significant reservoir for rickettsiae (no transovarial transmission)

BZ patients can serve as sources of infection for 1-5% of feeding lice!

Diagnosis Clinical manifestations often confused with

measles, meningococcemia, typhoid fever Weil-Felix reaction: IgM cross-reactive

with Proteus antigens (doesn’t work for BZ, non-specific, insensitive)

Specific serology: IFA Animal inoculation with patient’s blood

(yolk sac, guinea pig) Xenodiagnosis (infect previously

uninfected vectors) PCR of ticks found in clothing (Raoult, et

al)

Diagnosis

Treatment

Doxycycline, tetracycline, or chloramphenicol are very effective! Single dose of 200 mg doxycycline

Control and Prevention Sanitation!!!

Delousing of clothing, bedding with insecticide dust or temperatures >70oC for over 1 hour

Whole killed vaccine confers imperfect immunity

Live attenuated vaccine has been more successful in producing CMI, but has side effects, including mild disease

Typhus in History 430 BC - Plague of Athens during

Peloponnesian War? 1/3 of population died!

Clinical Manifestations 7-14 day incubation Fever (~ 2 weeks), chills, headache Macropapular rash after ~ 7 days,

centrifugal spread (unlike RMSF)

Myocarditis, stupor and delirium “typhos” (Greek) = smoke or haze

Typhus in History Napoleon in Moscow

WWI – epidemic in Russia (3 mil. deaths!), Poland, and Balkan States.

1909 – Charles Nicholle shows body louse is sole vector, influences improvements in sanitation during WWI (1928 Nobel Prize)

Typhus in History

WWII Vaccine used in armed forces Use of DDT significantly

decreased prevalence of typhus (1948 Nobel Prize goes to Paul Müller for discover of DDT)

Typhus rampant in concentration camps

Typhus Today Since WWII, typhus decreased to a few

foci, primarily in Burundi, Rwanda, and Ethiopia

HOWEVER, epidemics occurring in refugee camps and impoverished populations (Burundi, Russia)

Burundi, 1997

1993 – Civil war erupts, displacing over 760,000 refugees internally and throughout neighboring countries

1995 – “Jail Fever” outbreak in N’Gozi

1997 – 100,000 persons estimated to be infected throughout refugee camps in Burundi

Lessons from Burundi

Military blockades and civil war severely impaired investigation and management of epidemic

Rapid diagnostic techniques needed in the field to distinguish epidemic typhus in transient population

Treatment is cost-effective and essential, as delousing is difficult in transient populations

An effective and available vaccine is needed (all refugees in Burundi could be vaccinated in 2 months!)

“ Typhus is not dead. It will live on for centuries, and it will continue to break into the open whenever human stupidity and brutality give it a chance, as most likely they occasionally will.”

Hans ZinsserRats, Lice, and History (1934)