DR.SURINDER THAKURPROFESSOR OF MEDICINE, I.G.M.C., SHIMLA
A 38-year-old male, farmer admitted with Fever, bodyache -12 days, Shortness of breath -2 days Referred from peripheral health institution as no response to beta-lactam antibiotics. On examination the patient was conscious, febrile & in respiratory distress, BP-110/70 mm Hg, PR-110/min regular, RR-36/min JVP not raised, No-Cyanosis, No-Edema B/L Eschar in the axilla with tender lymphaedenopathy. ABDOMEN- Liver palpable, no spleenomegaly CHEST –B/L crepitations CVS & CNS -Normal
Showing two eschars in axillary region in a patient of scrub typhus.
Managed in ICU. I/V azithromycin 500 mg OD for 5 days. Discharged after 1 week.
Scrub typhus is a form of typhus caused by o.tsutsugamushi. First described in china 318 AD, isolated in Japan in 1930 Disease of rural villages and suburban areas. Term scrub is used because of the vegetation (terrain between woods and clearing) that harbours the vector. However certain endemic areas can be sandy semiaired and mountain deserts. Range tropical and temperate upto 3200 metres Scrub typhus often acquired during occupational /agricultural exposure. Scrub typhus is one of the underdiagnosed, underreported febrile illness requiring hospitalisation in the region [WHO]
Scrub typhus is endemic in tsutsugamushi triangle which extends from northern Japan, far eastern Russia in the north to the Northern Australia in the south and pakistan in the west. It was linked to war and military operations during the second world war, also important cause of PUO in U.S. forces during Vietnam conflict. Precise incidence of disease is unknown. Estimated 1 billion people are at risk of scrub typhus and estimated 1 million cases occur anually.
It is endemic in certain geographic regions of India, Indonesia, Maldives, Mayanmar, Nepal, Srilanka and Thailand. It has also been reported from various parts of India but specific data is not available. Seasonal occurence varies with the climate in different countries. Forrest clearing, river banks, grassy regions provide optimal conditions for infected mites to thrive.
Family rickettsiae, genus orientiae, Small obligate gram negative, intracellular bacteria. Cell wall lacks peptidoglycans and lipopolysaccharides. Serotypes identified Karp, Gilliam, Kawasaki, Boryon, Kato, Litchfield (in Australia). Primary reserviour, chigger/mite, larval stage,trombiculid mite(Leptotrombium daliense and others) Secondary reserviour rodents, humans. Incubation period 5-20 days, mean10-12 days.
Orientia tsutsugamushi is the causative agent & transmitted to humans through the bite of thrombiculid mites. The mites have a four-stage lifecycle: egg, larva, nymph and adult. The chigger (larval) phase is the only stage that is parasitic on animals or humans. Infection is maintained in nature transovarially from one generation of mite to the next.
Organism divides and breeds within the phagocytes and escape from the cell back into the circulation to continue to proliferate on the endothelium of small blood vessels releasing cytokines which damage endothelial integrity, causing fluid leakage, platelet aggregation, polymorphs and monocyte proliferation, leading to focal occlusive end-angiitis causing microinfarcts. It is now well established that a majority of sequelae associated with human rickettsioses are the outcome of‘Rickettsial vasculitis’. Especially affects skeletal muscles, skin, lungs, kidneys, brain and cardiac muscles.
Illness varies from mild and self limiting to fatal disease. Symptoms and signs varies in individuals with different strains. Commonest symptom high grade fever ,headache muscle pain ,cough, and GI symptoms. Severe disease in 2ND week. Meningitis , meningo-encephalitis , deafness, pneumonia, ARDS, MODS & myocarditis. Uncommon: dual infection with leptospira, typhoid. Reinfection & Relapses are seen due to variable immunity to different strains.
Maculopapular rash on the trunk<40%,often missed. Eschar in <50% in primary infection, <30% in endemic area and in reinfection. Lymphadenopathy regional and/or generalized.
Age Male Female Total % agegrp(years)0-18 5 7 12 5.4319-35 20 80 100 45.2536-55 12 61 73 33.03>55 11 25 36 16.29Total 48 173 221 100 250 200 150 Male 100 Female Total 50 0 0-18 19-35 36-55 >55 Total
SEXFEMALE 173(78%)MALE 48(22%) 22% FEMALE MALE 78%
OCCUPATIONFARMER 213(96%)OTHER 8(4%) OTHER 4% FARMER 96%
DISEASE OF RURAL AND SUBURBAN AREAS. DIAGNOSIS DIFFICULT IN ACUTE STAGE OF DISEASE. APPLICATION OF EPIDEMIOLOGICAL, CLINICAL AND LAB PRINCIPLES.
EPIDEMIOLOGICAL Exposure to vector & animal reservoir Travel to endemic region CLINICAL- ESCHAR & RASH LABORATORY Low wbc count Thrombocytopenia Elevated transaminases DEFINITIVE DIAGNOSIS Serology -paired sera
Isolationof organisms & Culture of organisms Serological tests for antibodies Weil Felix IFA Micro-immunofluroscence IIP ELISA Rapid Diagnostic reagent strips PCR-Blood, Buffy coat & Eschar. Genetic assays
Currently available serological tests for scrub typhus have limitations. Serological tests are more reliable when the titers show 4 fold rise in antibody titres for paired sample. Non endemic areas diagnosis can be made from single sample However cut of values used are identical irrespective of endemic and non endemic regions. Most frequently used antigen in IFA-karp, kato, & galliam. IN IgM ELISA antigen used is against outer membrane 56 kd protein from strains of karp, kato, galliam and boryon.
SERO Acute Spe Cost/ Time Ea Setting CommentsLOG sensit cific samp seY ivity ity leIFA ++ +++ ++++ 2hours ++ Reference • Serology gold standard, Requires propagation & purification of BSL3 agents lab/hospit as antigen for assay, Requires fluorescence al microscope, Standardization problems & Requires paired samples (retrospective diagnosis)IIP ++ +++ +++ 2hours ++ Reference -do- except requires light ++ lab/hospit microscope only alWeil- + ++ + 6-18 ++ Primary •Poor sensitivity for acuteFelix hours ++ hospital diseaseOXK2 • Requires paired samples (retrospective diagnosis)DIP- ++ +++ +++ <30 ++ Primary • Does not require specializedSTIC mins ++ hospital equipmentK + • Rapid and simple AM. J. TROP. MED. HYG., 82(3), 2010, PP. 368–370
WEIL FELIX ELISAPRINCIPLE HETEROPHILE AGGLUTINATION WITH RECOMBINANT ANTIGEN OF PROTEUS ANTIGEN ORIENTIATIME OVERNIGHT 2 HRSEASE OF SIMPLE BUT TIME CONSUMING EASY BUT TECHNICALLYPERFORMING DEMANDINGCOST CHEAP COST EFFECTIVENO OF SAMPLES PAIRED SERA ;FOUR FOLD RISE SINGLE SERA ;> CUT OFFREQUIREDRESULT SUBJECTIVE; NO CONSENSUS ON OBJECTIVE; CUT OFF BASEDINTERPRETATION SINGLE SIGNIFICANT TITRE ON CALCULATION ON NORMAL SERAANTIBODY TESTED MAINLY IgM SEPARATE ASSAYS FOR IgM AND IgGSENSITIVITY 30- 60 93-97SPECIFICITY 60- 90 91-95
ISOLA Acu Spe Cost/ Time Ea Setting CommentsTION te cific samp se sen ity le sitiv ityIN + +++ ++++ 7-60 + BSL3 • Isolation of BSL3 agentVITRO ++ + days Reference • Requires infrastructureISOLAT lab • Biocontainment issuesION • Retrospective diagnosisMOUSE + +++ ++++ 5-30 + BSL3 • Technically demandingINOCU ++ + days Reference • Isolation of BSL3 agentLATIO lab • Requires animal facilitiesN • Biocontainment issues • Retrospective diagnosis AM. J. TROP. MED. HYG., 82(3), 2010, PP. 368–370
GENET Acu Spe Cost/ Time Ea Setting CommentsIC te cific samp seTEST sen ity le sitiv ityREAL +++ +++ +++ 3 ++ Reference • Expensive equipmentTIME ++ hours + lab/hospit • Requires infrastructurePCR al • Sensitivity dependent on sample type and timing • Possible contamination issuesLOOP +++ +++ ++ 2 ++ Primary • SimpleAMPLI ++ hours ++ hospital • InexpensiveCATIO • Possible contaminationN issues AM. J. TROP. MED. HYG., 82(3), 2010, PP. 368–370
Doxycycline 100mg 1BD X 7-15 days. Tetracyclin 500mg Qid X 7-15 days. Chloromycetin 500mg Qid X 7-15 days. Azihromycin 500mg 1OD X 3 days. Pregnant mothers & childrens Azithromycin for 3 days. Rifampicin 600/900mg X 1OD for 1 week in resistant cases.
MORTALITY 7-30%. POOR PROGNOSIS Missed diagnosis Late presentation Drug resistance MODS ARDS
Avoidance of intrusion in areas infested with reservoir and vector. Proper clothing-Miticide and mite repellent, detection & removal. Rodent control-trapping, rodenticide, depriving food. Vector control-Ground treatment of residual vegetation with insecticide. No satisfactory vaccine-enormous antigenic variation of strains. Immunity of one strain doesnt offer immunity to other strains.
Recommended under special circumstances where disease is endemic. Oral chloramphenicol or tetracycline given once every 5 days for thirty-five days or weekly doses of doxycycline during and for 6 weeks after exposure have both been shown to be effective regimens. Resistance to antibiotics has been noted in several areas, therefore prophylaxis with antibiotics cannot be guaranteed.