Armed Forces Research Institute of Medical Sciences

EMERGING RICKETTSIAL DISEASES EMERGING RICKETTSIAL DISEASES IN ALONG THAI-MYANMAR BORDERIN ALONG THAI-MYANMAR BORDER

Armed Forces Research Institute of Armed Forces Research Institute of Medical Sciences, Bangkok, ThailandMedical Sciences, Bangkok, Thailand

Harvard School of Public Health, Boston, Harvard School of Public Health, Boston, USAUSA

Unité des Rickettsies, Marseille, FranceUnité des Rickettsies, Marseille, France

Philippe Parola, M.D., Ph.D.Philippe Parola, M.D., Ph.D.R. Scott Miller, M.D.R. Scott Miller, M.D.

Armed Forces Research Institute of Medical Sciences

WHAT ARE RICKETTSIAL WHAT ARE RICKETTSIAL DISEASES ? DISEASES ?

Infectious diseases caused by bacteria of the order Rickettsiales

Short, Gram-negative rods retaining basic fuchsin with Gimenez staining which live inside other cells

Taxonomy:

• Rickettsia : Spotted Fever Group Typhus group

• Ehrlichia, Anaplasma, Neorickettsia and Wolbachia

• Excluded from RickettsialesOrientia tsutsugamushi (scrub typhus)Coxiella burnetti (Q fever)Bartonella sp.

Armed Forces Research Institute of Medical SciencesWHAT ARE RICKETTSIAL WHAT ARE RICKETTSIAL

DISEASES ?DISEASES ?

ARTHROPOD BORNE DISEASES

TICKS: SFG rickettsioses, Ehrlichioses

• FLEAS: murine typhus (R. typhi), R. felis, Bartonella sp.

• LICE: epidemic typhus (R. prowazekii)

• TROMBICULIDS (chiggers): scrub typhus (O. tsutsugamushi)

I. ricinus in Europe

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12 tick-borne rickettsioses12 tick-borne rickettsioses 7 since 19917 since 1991 !! !!

R. rickettsii

R. africae

R. conorii

R. conorii

R. slovaca

R. conorii Astrakhan

R. conorii Israël

R. australis

R. honeiR. honei

Indian tick typhus Rickettsia

R. japonica

R. mongolotimonae

R. helvetica

R. mongolotimonae

R. sibirica

R. conorii

R. conorii Israël

« R. heilongjiangii »

R. helvetica

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Tick collection: flaggingTick collection: flagging

Rubber plantation

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Tick collection on animalsTick collection on animals

Dogs

Dog kennels

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BACKGROUNDBACKGROUNDRickettsial Diseases in ThailandRickettsial Diseases in Thailand

Murine Typhus due to R. typhiRat fleasKnow to occur in ThailandPoorly documented

Scrub typhus due to Orientia tsutsugamushiLeptotrombidium sp. (Chiggers)Endemic in Thailand, especially northern

region

NONE WELL DOCUMENTED IN THE SANGKHLABURI DISTRICT

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BACKGROUNDBACKGROUNDRickettsial Diseases in Thailand Rickettsial Diseases in Thailand

Few Cases of SFG rickettsioses documented by serologyin Thailand (Chiang Mai)

Sirisanthana et.al., Am J Trop Med Hyg 1994; 50: 682-6

Human Ehrlichioses in Thailand ?Heppner et al. Lancet 1997; 350: 785-6

AFRIMS/ Kwai River Clinical Center Fever Project July 1999-February 2000 150 febrile volunteers enrolled

• 3%: acute Spotted Fever Group rickettsioses (IF R. rickettsii antigen)• seroprevalence of SFG antibody in village surveys: 9% • seroprevalence of Ehrlichia spp. :

E. chaffeensis 2.8 % E. phagocytophila 5 %

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OBJECTIVESOBJECTIVES

AFRIMS study of the etiology of undifferentiated fever syndromes

• Determine whether ehrlichiosis and / or SFG rickettsiosis may serve as etiologic agents for fevers of unknown origin there.

• Identify potential vectors • Entomological risks

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• 3 cases of scrub typhus (O. tsutsugamushi)

• Scrub typhus is quite rare• 5% seroprevalance in 497 adults in Ban Viakadee and Ban Mong Satur

3 cases of murine typhus (R. typhi)

• 8 cases of SFG rickettioses (?)

14 CONFIRMED 14 CONFIRMED RICKETTSIOSES RICKETTSIOSES

in 2002in 2002

No ehrlichiosis documented in humans

Armed Forces Research Institute of Medical SciencesCases of scrub typhus : H H 535535

35-year-old Thai Man

Severe: 3-day fever + chills + headache + vomiting

Failure of a 5-day ceftriaxone

Recovered with Doxycycline

Removed multiple arthropods after jungle trips

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H 535: multiple bitesH 535: multiple bites

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H 541: 3 escharsH 541: 3 eschars

Shoulder: 4 cm Left calf: 3 cm Right calf: 4 cm

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H 541: Macular rashH 541: Macular rash

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Serology IF (IgG/IgM) Acute LateO. tsutsugamushi Gilliam 128/64128/16

Karp 0/0 0/0Kato 0/0 0/0Kawazaki 0/0 0/0

R. japonica 0/32 0/32R. helvetica 0/32 0/32R. honei 0/16 0/16

PCR biopsy: negativeBiopsy/Blood culture: negative

H 541: diagnosisH 541: diagnosis

Armed Forces Research Institute of Medical SciencesCases of murine typhus: R. typhi

Age

(y)Fever Diffuse

Rash

Eschars Local Nodes

Other IF R. typhi

TITERSIgG/IgM

35 Yes No No Femoral left

ChillinessChills

Headache

N°1: 16/256N°2: 512/256

37 Yes No No No ChillinessChills

Headache

Nausea vomiting

N°1: 64/8N°2: 512/256

20 Yes No No No Headache N°1: 0/64

N°2: 128/256

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Cases of SFG rickettsioses

49-year-old Karen Woman3-day Fever + ChillsEmpiric TRT: cotrimoxazoleRecovered

Retrospective questionning:Removed a tick from her body10 days prior fever

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H 492: tick-bite escharH 492: tick-bite eschar

3 weeks3 weeksafter removing the tickafter removing the tick

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Cases of SFG rickettsiosesR. conorii - like

Age Fever Rash Eschar Nodes Other IF SFGIgG/IgM

50 Yes

Severe

Illness

Yes YesLeft Knee

No Chills

Abdom. Pain

Rales

Confusion

Low PLTs

Anemia

R. conorii Indian

N°1: 128/16

N°2: 128/16

45

Jungle trips

Yes

Severe

illness

No No No Nausea

Vomiting

Diarrhea

HMG

SPM

R. conorii Indian

N°1: 64/32

N°2: 64/32

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Cases of SFG rickettsiosesR. helvetica - like

Age Fever Rash Eschar Nodes Other IF SFGIgG/IgM

35Jungle trips

Tick bite one

week before

Yes

Severeillness

No Yes heaped edge

0.8 cm

No ChillinessHeadache

Nausea vomitingCoughingMyalgiaHMG

WBC 14

R. helvetica

N°1: 64/256

N°2: 16/128

37Tick bite not noted

Yes Yes ? No No HeadacheChilliness

Nausea vomitingCoughingMyalgia

WBC 19.8LFTs

R. helvetica

N°1: 0/16

N°2: 128/32

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CONCLUSIONSCONCLUSIONS

Rickettsial disease as a cause of fever in the Thai-Burma Border, Sangkhlaburi district, Thailand include:

• Scrub typhus• Murine typhus• SFG rickettsioses

SFG Rickettsioses – not previously described in Thailand • R. conorii India ? R. helvetica ?• Other cross reacting rickettsia or new species ?• \

• Clinically all respond well to doxycycline

for 7 days

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Fever Study Conclusions• Most fevers are difficult to classify by organ involvement

– Rapid diagnostic tests are needed

• Leptospirosis is common and underrecognized– ~7% of fevers in adults coming to hospital

– Major cause of morbidity and febrile jaundice

– Further epidemiology studies are needed

• There are 3 other rickettsial illnesses in addition to scrub typhus. Not all have rash or eschar.

• All respond well to doxycycline or tetracycline