10 Rickettsial Diseases 立克次體病 Rickettsiae are obligate intracellular gram-negative coccobacilli and short bacilli(屬於絕對細胞內寄生的革蘭氏陰性立克次體科細菌)Usually transmitted by tick, mite, flea, or louse vectors.Except in the case of louse-borne typhus, humans are incidental hosts.行政院衛生署疾病管制局 人畜共通傳染病臨床指引 A Clinical Guide to Zoonoses
11 Rickettsial Diseases立克次體病 依據16S rRNA序列立克次體亦可明顯分為3群，斑點熱群（spotted fever group rickettsia；SFG）立克次體，為立克次體中依抗原性分為3群中最複雜的一群，種類也最多。斑疹傷寒群（typhus group；TG）恙蟲病（又稱叢林型斑疹傷寒）。行政院衛生署疾病管制局 人畜共通傳染病臨床指引 A Clinical Guide to Zoonoses
16 KARP-related, Gilliam, TA763, JG, JG-v, and KATO-related in Taiwan. Phylogenetic tree of O. tsutsugamushi based on the nucleotide sequences of the 56-kDa cell surface antigen gene.KARP-related, Gilliam, TA763, JG, JG-v, and KATO-related in Taiwan.Phylogenetic tree of O. tsutsugamushi based on the nucleotide sequences of the 56-kDa cell surface antigen gene. The subset of the phylogenetic tree is made up of isolates (strains from this study are indicated by open circles) associated with clades with sequence divergence from the reference strains (filled circles), such as Karp, Gilliam-related strains, and Kato, and strains isolated from humans (no mark). Isolates are identified by their GenBank accession numbers. Phylogenetic analyses were conducted using MEGA4. The evolutionary history was inferred using the neighbor-joining method and a bootstrap test on 1,000 replicates.Lin P et al. Appl. Environ. Microbiol. 2011; doi: /AEM
18 Map of the geographic areas in Taiwan showing O Map of the geographic areas in Taiwan showing O. tsutsugamushi strains isolated in scrub typhus patient. 2011縣市名稱合計台北市14基隆市新北市(台北縣)10宜蘭縣2金門縣77連江縣19新竹市1桃園縣3新竹縣苗栗縣台中市12彰化縣6南投縣13台南市嘉義市雲林縣嘉義縣4高雄市22屏東縣澎湖縣花蓮縣33台東縣42293
33 Pediatric Scrub Typhus in Eastern Taiwan Scrub typhus should be considered in children with fever and hepatic dysfunction, particularly in those with a history of environmental exposure in an endemic area for scrub typhus.Eschar offers an important diagnostic clue, but not for all cases.Children with scrub typhus may develop serious complications and may even die if appropriate treatment is not given.Doxycycline is an effective antibiotic for pediatric scrub typhus in Taiwan.Pediatr Neonatol 2009;50(3):96−101
34 Complications of Scrub Typhus No. of patients (%)Pneumonia12(36)ARDS5(15)ARF3(9)Myocarditis1(3)Septic shockData from Clinical Radiology (2000) 55, 140–144Journal of the American Academy of Nurse Practitioners 24 (2012) 160–165
35 An 81-year-old woman with scrub typhus An 81-year-old woman with scrub typhus. Initially, bilateral extensive consolidation is visible mainly in the lower zones. Cardiomegaly, pulmonary oedema and pleural effusions are also present.Clinical Radiology (2000) 55, 140–144
36 Follow-up chest radiograph taken 10 days later, after treatment with doxycycline, shows clearing of both lower lungs and pleural effusions and a decrease in cardiac size.Clinical Radiology (2000) 55, 140–144
39 Scrub Typhus-Associated Central Nervous System Complications Meningoencephalitis1,5Acute Disseminated Encephalomyelitis2Scrub typhus complicated by intracranial hemorrhage - A Case report.3Acute transverse myelitis4Ann Indian Acad Neurol 2012;15:141-4.Acta Neurol Taiwan 2006;15:Tzu Chi Med J 2005;17:111-4. Diagn Microbiol Infect Dis. 2008;60(2):237-9.Arch Neurol 2000;57:1770-2
40 Differentiate Diagnosis Coinfection with Leptospirosis and Scrub Typhus in Taiwanese Patients1The clinical differences between dengue and scrub typhus with acute respiratory failure in southern Taiwan2Acute Q fever and scrub typhus, southern Taiwan3Clinical Manifestations and Complications of Rickettsiosis in Southern Taiwan4Acute Q feverScrub typhusMurine typhus Am J Trop Med Hyg. 2007; 77(3): 525–527.Infection 2012, DOI: /sEmerg Infect Dis. 2009; 15(10): 1659–1661.J Formos Med Assoc. 2002;101:385–92.
48 Summary of key treatment studies in scrub typhus DrugsAuthor/YearType of studyKey findingChloramphenicol VS tetracyclineSheehyet al.1973CTTetracycline superior to chloramphenicolDoxycycline 200 mg SD VS tetracycline 100 mg QID 7 daysBrownet al.1978RCTdoxycycline as effective as tetracyclineDoxycycline 100 mg BID 3 days VS tetracycline 100 mg QID 7 daysSonget al.1995doxycycline as effective as tetracyclineAzithromycin 500 mg SD VS doxycycline 200 mg Daily 7 daysKim et al.2004Azithromycin equally effective as doxycycline .Defervescence slightly longer with doxycycline.Less gastrointestinal adverse effects with azithromycinAzithromycin 500 mg 3 days VS doxycycline 200 mg 7 daysPhimdaet al.2007Azithromycin 3-day equally effective as doxycycline. Defervescence longer with azithromycin.Telithromycin 800 mg daily 5 days VS doxycycline 200 mg 5 daysQuasi-RCTTeilithromycin as effective as doxycyclineRifampicin 600 mg/900 mg VS doxycycline 200 mg 7 daysWattet al. 2000Rifampicin superior to doxycycline–faster defervescence, fewer relapses (trial was in a geographical locality where doxycycline resistance was known to occur)Levofloxacin VS tetracyclinesTsaiet al.2010Retrospective analysisLevofloxacin as effective as tetracyclines.Longer time to defervescence with levofloxacin.Higher mortality with levofloxacin in severe diseaseTrop Doct January 2011 vol. 41 no. 1 1-4RCT:Randomized controlled trialTrop Doct January 2011 vol. 41 no. 1 1-4
49 Intravenous Minocycline Versus Oral Doxycycline for the Treatment of Noncomplicated Scrub Typhus Conclusion:Both antibiotics have similar efficacy for the treatment of noncomplicated scrub typhus.Nearly all cases responding to both antibiotics became afebrile within 3 days.Journal of Microbiology, Immunology and Infection. 2011; 44:33-38
50 Levofloxacin Versus Tetracycline Antibiotics for the Treatment of Scrub Typhus Conclusions:Levofloxacin is effective in patients with scrub typhus, but has a longer time to defervescence compared with tetracycline antibiotics.When levofloxacin is used for severe scrub typhus, higher mortality may be attributed to the longer time to defervescence.Kaplan—Meier curve of the time to defervescence in patients initially treated with levofloxacin and tetracycline antibiotics ( p = ).International Journal of Infectious Diseases;2010:14, e62—e67.
51 Treatment of O. tsutsugamushi Infection Tetracycline, doxycycline, or chloramphenicol is used to treat scrub typhus.Minocin 200mg/ IV/ st., 100mg/ IV/ q12hDoxycycline 100mg/ P.O./ q12h, for 14 daysChloramphenicol-resistant & doxycycline-resistant strains of O tsutsugamushi occur in the areas of northern Thailand.#Oral azithromycin was administered in a 500-mg dose on the first day, followed by 250 mg daily on days 2 to 5.* in children and pregnant women.#Lancet 1996 Jul 13;348(9020):86-9*Antimicrob. Agents Chemother. 1999, 43:
53 References, Web sites and Further readings Center for Disease Control Taiwan, ROC，台灣疾病管制局Centers for Disease Control and Prevention, U.S.A,World Health Organization,Mandell, Gerald L. et al. Principles and Practice of Infectious Disease. Sixth Edition Churchill Livingstone. October 22, ppTimmreck, Thomas C. An Introduction to Epidemiology. 2nd ed Jones & Bartlett Publishers, Inc. Boston, United States of America.CDC, Principles of Epidemiology. 3nd ed Atlanta, GA: Centers for Disease Control and Prevention.Wolfgang, A & Iris, P. Handbook of Epidemiology. 1st ed Springer-Verlag Berlin Heidelberg , Germany.Fred, B.; Pauline, van den D. ; Jianhong, W. Mathematical Epidemiology Springer-Verlag Berlin Heidelberg , Germany.Richard D.T. Farmer, Ross Lawrenson. Lecture notes on epidemiology and public health medicine. 5th ed Blackwell Publishing, Inc., Massachusetts, USA.Stefan Ma. Mathematical Understanding of Infectious Disease Dynamics World Scientific Publishing.Bonita R., R. Beaglehole, T. Kjellstrom. Basic epidemiology. 2nd ed. World Health Organization, 2006.