AFRIMS-GEIS Five-Year Strategic Plan

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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
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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 Spotted Fever Group
• Typhus group
• Ehrlichia, Anaplasma, Neorickettsia and
  Wolbachia
• 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,
• 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 Leptotrombid
ium 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
  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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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 vomiting Failure of a 5-day
ceftriaxone Recovered with Doxycycline
Removed multiple arthropods after jungle trips
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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 Karp 0/0
0/0 Kato 0/0 0/0 Kawazaki 0/0 0/0 R.
japonica 0/32 0/32 R. helvetica 0/32 0/3
2 R. honei 0/16 0/16 PCR biopsy
negative Biopsy/Blood culture negative
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Cases of murine typhus R. typhi
Age (y) Fever Diffuse Rash Eschars Local Nodes Other IF R. typhi TITERS IgG/IgM
35 Yes No No Femoral left Chilliness Chills Headache N1 16/256 N2 512/256
37 Yes No No No Chilliness Chills Headache Nausea vomiting N1 64/8 N2 512/256
20 Yes No No No Headache N1 0/64 N2 128/256
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Cases of SFG rickettsioses
49-year-old Karen Woman 3-day Fever
Chills Empiric TRT cotrimoxazole Recovered
Retrospective questionning 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 rickettsiosesR. conorii - like
Age Fever Rash Eschar Nodes Other IF SFG IgG/IgM
50 Yes Severe Illness Yes Yes Left Knee No Chills Abdom. Pain Rales Confusion Low PLTs Anemia R. conorii Indian N1 128/16 N2 128/16
45 Jungle trips Yes Severe illness No No No Nausea Vomiting Diarrhea HMG SPM R. conorii Indian N1 64/32 N2 64/32
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Cases of SFG rickettsiosesR. helvetica - like
Age Fever Rash Eschar Nodes Other IF SFG IgG/IgM
35 Jungle trips Tick bite one week before Yes Severe illness No Yes heaped edge 0.8 cm No Chilliness Headache Nausea vomiting Coughing Myalgia HMG WBC 14 R. helvetica N1 64/256 N2 16/128
37 Tick bite not noted Yes Yes ? No No Headache Chilliness Nausea vomiting Coughing Myalgia WBC 19.8 LFTs R. helvetica N1 0/16 N2 128/32
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CONCLUSIONS

• 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