Transcript AFRIMS-GEIS Five-Year Strategic Plan

Armed Forces Research Institute of Medical Sciences
EMERGING RICKETTSIAL DISEASES
IN ALONG THAI-MYANMAR BORDER
Philippe Parola, M.D., Ph.D.
R. Scott Miller, M.D.
Armed Forces Research Institute of Medical
Sciences, Bangkok, Thailand
Harvard School of Public Health, Boston, USA
Unité des Rickettsies, Marseille, France
Armed Forces Research Institute of Medical Sciences
WHAT ARE RICKETTSIAL 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 :
•
Ehrlichia, Anaplasma, Neorickettsia and Wolbachia
Spotted Fever Group
Typhus group
• Excluded from Rickettsiales
Orientia tsutsugamushi (scrub typhus)
Coxiella burnetti (Q fever)
Bartonella sp.
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WHAT ARE RICKETTSIAL DISEASES ?
ARTHROPOD BORNE DISEASES
TICKS: SFG rickettsioses, Ehrlichioses
•
FLEAS: murine typhus (R. typhi), R. felis,
I. ricinus in Europe
Bartonella sp.
•
LICE: epidemic typhus (R. prowazekii)
•
TROMBICULIDS (chiggers): scrub typhus
(O. tsutsugamushi)
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12 tick-borne rickettsioses
7 since 1991 !!
R. mongolotimonae
R. conorii Astrakhan
R. sibirica
R. helvetica
« R. heilongjiangii »
R. mongolotimonae
R. conorii Israël
R. helvetica
R.
slovaca
R. conorii
R. conorii Israël
R. japonica
R. conorii
R. rickettsii
Indian tick typhus Rickettsia
R. conorii
R. australis
R. africae
R. honei
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Tick collection: flagging
Rubber plantation
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Tick collection on animals
Dogs
Dog kennels
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BACKGROUND
Rickettsial Diseases in Thailand
Murine Typhus due to R. typhi
Rat fleas
Know to occur in Thailand
Poorly documented
Scrub typhus due to Orientia tsutsugamushi
Leptotrombidium sp. (Chiggers)
Endemic in Thailand, especially northern region
NONE WELL DOCUMENTED IN THE
SANGKHLABURI DISTRICT
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BACKGROUND
Rickettsial Diseases in Thailand
Few Cases of SFG rickettsioses documented by serology
in 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 enrolle
• 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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OBJECTIVES
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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14 CONFIRMED RICKETTSIOSES
in 2002
• 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 (?)
No ehrlichiosis documented in humans
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Cases of scrub typhus : H 535
35-year-old Thai Man
Severe: 3-day fever
+ chills + headache + vomitin
Failure of a 5-day ceftriaxon
Recovered with Doxycycline
Removed multiple arthropods after jungle trip
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H 535: multiple bites
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H 541: 3 eschars
Shoulder: 4 cm
Left calf: 3 cm
Right calf: 4 cm
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H 541: Macular rash
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H 541: diagnosis
Serology IF (IgG/IgM)
Acute
Late
O. tsutsugamushi Gilliam
128/64
128/16
0/0
0/0
0/0
0/0
0/0
0/0
0/32
0/32
0/16
0/32
0/32
0/16
Karp
Kato
Kawazaki
R. japonica
R. helvetica
R. honei
PCR biopsy: negative
Biopsy/Blood culture: negative
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Cases of murine typhus: R. typhi
IF R.
typhi
TITERS
IgG/IgM
Age
(y)
Fever
Diffuse
Rash
Eschars
Local
Nodes
Other
35
Yes
No
No
Femoral
left
Chilliness
Chills
Headach
e
N°1:
16/256
N°2:
512/256
37
Yes
No
No
No
Chilliness
Chills
Headach
e
Nausea
vomiting
N°1: 64/8
N°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 Woman
3-day Fever + Chills
Empiric TRT: cotrimoxazol
Recovered
Retrospective questionnin
Removed a tick
from her body
10 days prior fever
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H 492: tick-bite eschar
3 weeks
after removing the tick
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Cases of SFG rickettsioses
R. conorii - like
Age
Fever
Rash
Eschar
Nodes
Other
IF SFG
IgG/IgM
50
Yes
Yes
Yes
No
Chills
Abdom. Pain
Rales
Confusion
Low PLTs
Anemia
R. conorii
Indian
Left
Knee
Severe
Illness
45
Yes
Jungle
trips
Severe
illness
No
No
No
Nausea
Vomiting
Diarrhea
HMG
SPM
N°1: 128/16
N°2: 128/16
R. conorii
Indian
N°1: 64/32
N°2: 64/32
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Cases of SFG rickettsioses
R. helvetica - like
Age
Fever
Rash
Eschar
Nodes
Other
IF SFG
IgG/IgM
35
Yes
No
Yes
No
Chilliness
Headache
Nausea
vomiting
Coughing
Myalgia
HMG
WBC 14
R. helvetica
Headache
Chilliness
Nausea vomiting
Coughing
Myalgia
WBC 19.8
LFTs
R. helvetica
Jungle
trips
Tick bite
one
week
before
37
Tick bite
not noted
heaped
edge
0.8 cm
Severe
illness
Yes
Yes ?
No
No
N°1: 64/256
N°2: 16/128
N°1: 0/16
N°2: 128/32
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CONCLUSIONS
Rickettsial disease as a cause of fever in the ThaiBurma 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