CAPPADOCIA, TURQUIECAPPADOCIA, TURQUIE15 juin 201015 juin 2010

«« Microorganisms Microorganisms associated with liceassociated with lice»»

Didier RaoultMarseille – France

didier.raoult@gmail.com UR

Body louse transmitted Body louse transmitted diseasesdiseases

Rickettsia prowazekii

Borrelia recurrentis

Bartonella quintana

Acinetobacter baumanii?

Yersina pestis?

PLoS One. 2008 Mar 19;3(3):e1805

Feeding louseFeeding louse

Injects :

- Anesthetic and anti-coagulant substances with subsequent allergy

- Induces species -specific vasodilatationScratching and inoculation

Defecation Sample blood

Body Lice and their InfectingBody Lice and their InfectingBacteria Around the WorldBacteria Around the World

PeruR. prowazekii

B. quintana BurundiB. quintana

R. prowazekii

SoudanB. recurrentis

AlgeriaR. prowazekii

RussiaR. prowazekii

B. quintana

FranceB. quintana

ZimbabweB. quintana

Tested lice since 5 years (2002)Country Number Positive

B. quintanaPositiveR. prowazekii

PositiveB. recurentis

Congo 7 0 0 0Burundi outbreak Jail Camps Post outbreak 1998 Post outbreak 2000 Refugee camp 2001Rwanda Jail 2001

106312911133262

08 %16 %90 %94%2%

20 %22 %0021%7%

000000

Zimbabwe 12 17 % 0 0France: Homeless shelter 1998-2002

1241 26% 00

00

Tunisia 3 0 0 0Peru Andes OthersChina

731023

1 %00

000

000

NetherlandRussia Homeless 1998Tunisia Homeless 2000Algeria Homeless 2001Australia Homeless 2001

252683332

36%12%000

00000

00000

Bod

y lic

e

France, Portugal, Russia,Algeria, Burundi, China, Thailand, Australia

143 0 0 0Head lice

UR

Medicine (Baltimore). 2005 Jan;84(1):61-8

1760: Boissier de Sauvage squoted the name typhus exanthematique

1903: Nicolle noticed that patients admitted in the hospital after changes of their garnments were no more contagious. He suspectedbody lice.

1909: Nicolle

- Inoculated a chimpanzee with a patient’s blood

- Chimpanzee to Macacus (blood)

Macacus to Macacus (lice)

1911: Inoculation of Guinea pig (Ch. Nicolle)

1914: Sergent identified R. prowazekii in lice

1928: Nobel Prize for Charles Nicolle

Typhus studiesTyphus studies

Epidemic typhusEpidemic typhus(Jail fever, Red louse fever)(Jail fever, Red louse fever)

Rickettsia prowazekiiVector : Body (not head) louseLarge outbreak in Burundi (100.000 cases in 1997) Foci in Peru, Ethiopia, Rwanda, Algeria, RussiaFever - Eruption : 30 - 60 %10-30% mortality when not treatedTreatment : single 200 mg dose of Doxycycline

10-100 cases101-1,000 casesover 1,000 cases Typhus in the 80's

Typhus epidemiologyTyphus epidemiology

InfectionTyphus Apparent

cure(Years)

RelapseBrill Zinsser Disease

Cold weatherBad hygiene

WARStress

Body liceoutbreak

Infected lice

TYPHUSOUTBREAK

Index case: a Swiss nurse with fever returning from Burundi jail, treated as Typhoid and died

Zanetti G, Francioli P, Tagan D, Paddock CD, Zaki SR. Imported epidemic typhus.

Lancet. 1998 ;352:1709.

Small Outbreak: investigated in a Burundi jail

Typhus Outbreak Typhus Outbreak BurundiBurundi

Raoult D, Roux V, Ndihokubwayo JB, Bise G, Baudon D, Marte G, Birtles R.Jail fever (epidemic typhus) outbreak in Burundi.

Emerg Infect Dis. 1997;3:357-60.

GIANT OUTBREAKGIANT OUTBREAKNew diseaseNew disease ::"SUTAMA" (Crouching)

Fever, severe myalgias of the legs, headache, resistance to antimalarial drugs, presence of body lice103 patients were sampled(serum and body louse)70 % of them had biological confirmation of epidemic typhus

Typhus Outbreak Typhus Outbreak BurundiBurundi

Estimated cases: 100,000 in 1997

(D. Raoult, et al. Lancet, 1998, 352: 353-358)

Clinical symptoms and laboratory data for patients withClinical symptoms and laboratory data for patients withepidemicepidemic typhustyphus

1997 :Typhus in Burundi1997 :Typhus in Burundi

100.000 cases100.000 cases

UR

UR

Severe Typhus Severe Typhus

Typhus sporadic cases Typhus sporadic cases

Russia: 1997: 23 cases in a psychiatric institution(Tarasevich I, et al. 1998, Lancet, 352: 1151)

Peru: outbreak near Cusco(Raoult D., et al. 1999, Clin Infect Dis, 29: 434-

436)

Algeria: cases near Batna (1998-2003)(Niang M, et al. 1999, Emerg Infect Dis. 5:716-718Mokrani K, et al. 2004, J Clin Microbiol, 42:3898-

3900)

France: a case in a homeless(Brouqui P, et al. Medicine (Baltimore). 2005;

84:61-8)

Napoleon Retreat of RussiaNapoleon Retreat of Russia

VilniusVilnius--cemetery 2002cemetery 2002

UR

Finding ancient lice in the graves of Finding ancient lice in the graves of Napoleon soldiersNapoleon soldiers

Lice floating on kerosene

The dental pulpThe dental pulp: : an answer to the material questionan answer to the material question

Preserved from external wash-out and contaminationLong-term preservedHighly vascularized: bacteremic pathogensDNA easy to extract

The dentistThe dentistUR

We extracted DNA from dental pulp of 35 soldiers and found B. quintana in 7 and R. prowazekii in 3.

In conclusion 30% of Napoleon’s soldiers suffered

louse borne disease. UR

Confirmed outbreak of the past:

-Yersinia pestis (Justinian Plague (VIth century)

-Black death (XIVth)

-S. Typhi (Athenian Plague: Vth century)

- Typhus Napoleon Retreat (XIXth)

UR

Bartonella quintanaBartonella quintana1917 : Trench fever1992 : Bacillary angiomatosis1993 : Endocarditis in an HIV patient1994 : Chronic lymphadenopathy 1995 : Endocarditis 1995 : Chronic bacteremia 1995 : Urban trench fever 1998 : Meningoencephalitis1999 : Asymptomatic bacteremia

UR

Epidemiology of Epidemiology of B. quintanaB. quintanainfectionsinfections

Reservoir: humansVector: human body louseRisk factors :– homelessness– chronic alcoholism– louse infestation

Ticks?Fleas? Intravenous injection?Cat? U

R

Trench feverTrench fever

B. (Rochalimaea) quintanaWorld Wars I and II"quintan fever"persistent bacteremia withpain in the bones 5 day-recurrencesvector : human body lousePediculus humanis corporis

Trench by Otto Dix

UR

B. quintanaB. quintana bacteremia in the bacteremia in the homelesshomeless

"urban trench fever"Persistent bacteremia: Marseille, FranceSeattle, USARisk factors: homelessnesschronic alcoholismlouse infestation

UR

Association of bacteremia with clinical and Association of bacteremia with clinical and biological symptoms (1997biological symptoms (1997--2001) 43 patients 2001) 43 patients

samples systematicallysamples systematically

Not significant (tested vs non bacteremic homeless)- age, sex, alcoholism, smoking habits, presence of lice- fatigue, weight loss, vertigo, anorexia, fever, headaches, arthralgias, myalgias, hepatomegaly, splenomegaly, pain in the limbs, cardiac murmur- hyperleucocytosis, increase transaminases, increase g glutamyl transferase, anemia, increase erythrocyte size

Significantly different- homeless for less then 2 years- B. quintana positive louse- B. quintana positive serology- high antibody titers- sweats

UR

Chronic bacteremiaChronic bacteremia

Described in louse feeding volunteers in Poland (Weigl vaccine)Late relapses and intermittent bacteremia (up to 8 years)In our population 6/10 patients with bacteremia will relapse after one month without treatmentIt is not prevented by doxycycline (3/5 relapsed) or Betalactams (3/4)Treated by gentamycin and doxycycline did not relapsed (significant difference)

UR

BartonellaBartonella quintanaquintana and humans and humans

The Body Louse as a Vector of Reemerging Human DiseasesD.Raoult and V.Roux

PlaguesPlagues!!

The The biovarbiovar theorytheory: : 3 plague pandemics3 plague pandemics

- Justinian plague antigua

- Medieval plague medievalis

- Modern plague (Hong Kong) orientalis

Molecular diagnosis of Justinian plagueMolecular diagnosis of Justinian plague

• Drancourt M, et al. Genotyping Orientalis like Yersinia pestis, and Plague pandemics. Emerg Infect Dis. 2004;10:1585-92.

Genotyping ancient Genotyping ancient Y. Y. pestispestisstrains strains

Y. pestis comprises three biotypes/genotypes: antiqua, medievalis, orientalisAre biotypes each responsible for one pandemia ?Two Y. pestis genomes are available

Drancourt M, et al.Yersinia pestis Orientalis in remains of ancient plague patients. Emerg Infect Dis. 2007;13:332-3.

Plague Plague ConclusionsConclusions

The 3 “plague pandemics”were caused

by Yersinia pestis orientalis

Proposed model for large human plague epidemics through Proposed model for large human plague epidemics through human human ectoparasiteectoparasite--borne transmission of borne transmission of Y Y pestispestis