title: Orientia, rickettsia, and leptospira pathogens as causes of CNS infections in Laos: a prospective study.
abstract: BACKGROUND
  Scrub typhus (caused by Orientia tsutsugamushi), murine typhus (caused by Rickettsia typhi), and leptospirosis are common causes of febrile illness in Asia; meningitis and meningoencephalitis are severe complications. However, scarce data exist for the burden of these pathogens in patients with CNS disease in endemic countries. Laos is representative of vast economically poor rural areas in Asia with little medical information to guide public health policy. We assessed whether these pathogens are important causes of CNS infections in Laos.
  
  
  METHODS
  Between Jan 10, 2003, and Nov 25, 2011, we enrolled 1112 consecutive patients of all ages admitted with CNS symptoms or signs requiring a lumbar puncture at Mahosot Hospital, Vientiane, Laos. Microbiological examinations (culture, PCR, and serology) targeted so-called conventional bacterial infections (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, S suis) and O tsutsugamushi, Rickettsia typhi/Rickettsia spp, and Leptospira spp infections in blood or cerebrospinal fluid (CSF). We analysed and compared causes and clinical and CSF characteristics between patient groups.
  
  
  RESULTS
  1051 (95%) of 1112 patients who presented had CSF available for analysis, of whom 254 (24%) had a CNS infection attributable to a bacterial or fungal pathogen. 90 (35%) of these 254 infections were caused by O tsutsugamushi, R typhi/Rickettsia spp, or Leptospira spp. These pathogens were significantly more frequent than conventional bacterial infections (90/1051 [9%] vs 42/1051 [4%]; p<0·0001) by use of conservative diagnostic definitions. CNS infections had a high mortality (236/876 [27%]), with 18% (13/71) for R typhi/Rickettsia spp, O tsutsugamushi, and Leptospira spp combined, and 33% (13/39) for conventional bacterial infections (p=0·076).
  
  
  CONCLUSIONS
  Our data suggest that R typhi/Rickettsia spp, O tsutsugamushi, and Leptospira spp infections are important causes of CNS infections in Laos. Antibiotics, such as tetracyclines, needed for the treatment of murine typhus and scrub typhus, are not routinely advised for empirical treatment of CNS infections. These severely neglected infections represent a potentially large proportion of treatable CNS disease burden across vast endemic areas and need more attention.
  
  
  BACKGROUND
  Wellcome Trust UK.
authors.affiliation: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Churchill Hospital, University of Oxford, Oxford, UK.
authors.forename: Sabine
authors.initials: S
authors.lastname: Dittrich
authors.affiliation: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.
authors.forename: Sayaphet
authors.initials: S
authors.lastname: Rattanavong
authors.affiliation: Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Churchill Hospital, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Sue J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.
authors.forename: Phonepasith
authors.initials: P
authors.lastname: Panyanivong
authors.affiliation: University of the Sunshine Coast, Faculty of Science Health, Education and Engineering, Sippy Downs, Australia; Queensland Health Forensic and Scientific Service, WHO Collaborating Centre for Reference and Research on Leptospirosis, Brisbane, Australia.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Craig
authors.affiliation: Queensland Health Forensic and Scientific Service, WHO Collaborating Centre for Reference and Research on Leptospirosis, Brisbane, Australia; Copenhagen Centre for Disaster Research Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Suhella M
authors.initials: SM
authors.lastname: Tulsiani
authors.affiliation: Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Churchill Hospital, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Blacksell
authors.affiliation: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Churchill Hospital, University of Oxford, Oxford, UK.
authors.forename: David A B
authors.initials: DA
authors.lastname: Dance
authors.affiliation: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Churchill Hospital, University of Oxford, Oxford, UK; UMR_D 190 "Emergence des Pathologies Virales", Aix-Marseille University, IRD French Institute of Research for Development, EHESP French School of Public Health, Marseille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Dubot-Pérès
authors.affiliation: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.
authors.forename: Amphone
authors.initials: A
authors.lastname: Sengduangphachanh
authors.affiliation: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.
authors.forename: Phonelavanh
authors.initials: P
authors.lastname: Phoumin
authors.affiliation: Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Churchill Hospital, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Paris
authors.affiliation: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Churchill Hospital, University of Oxford, Oxford, UK. Electronic address: paul@tropmedres.ac.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004660:Encephalitis / Q000453:epidemiology / Q000382:microbiology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007812:Laos / Q000453:epidemiology; D007919:Leptospira / Q000302:isolation & purification*; D008297:Male; D008581:Meningitis / Q000453:epidemiology / Q000382:microbiology*; D008875:Middle Aged; D012285:Orientia tsutsugamushi / Q000302:isolation & purification*; D011446:Prospective Studies; D012281:Rickettsia / Q000302:isolation & purification*; D055815:Young Adult