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APPROACH TO RICKETTSIAL
INFECTIONS
DR.K SURENDER ASSOC PROFESSOR
DEPARTMENT OF PEDIATRICS KAKATIYA
MEDICAL COLLEGE WARANGAL
INTRODUCTION
• EMERGING INFECTION
• EARLY NON SPECIFIC SIGNS AND SYMPTOMS
• PROGRESSES WITH FATAL OUTCOMES >30%
CASE FATALITY IN UNTREATED OR DELAY
• DIAGNOSTIC DIFFICULTIES
• BETTER OUTCOME WITH EARLY INITIATION OF
TREATMENT
ETIOLOGY
• MOTILE GRAM NEGATIVE, NON SPORE
FORMING, PLEOMORPHIC BACTERIA
• OBLIGATE INTRACELLULAR PARASITE
• MAJOR ANTIGENS ARE LPS, LIPOPROTEIN,
OMP-A, OMP-B
• GROWTH IS ENHANCED BY SULPHONAMIDES
CLASSIFICATION
SNO DISESASE RICKETSIAL
AGENT
INSECT
VECTOR
MAMMALIAN
RESORVOIR
1 TYPHUS GROUP
EPIDEMIC TYPHUS R. PROWAZEKII LOUSE HUMANS
MURINE TYPHUS R. TYPHI FLEA RODENT
SCRUB TYPHUS R.
TSUTSUGAMUS
HI
MITE RODENT
2 SPOTTED FEVER
GROUP
RMSF R. RICKETTSII TICK DOG/RODENT
INDIAN TICK TYPHUS R. CONORII TICK DOG/RODENT
TICK BORNE
LYMPHADENOPATHY
R. SLOVACA TICK WILD BORE
SNO DISESASE RICKETSSIAL
AGENT
INSECT
VECTOR
MAMALLIAN
AGENT
3 TRANSITIONAL
GROUP
RICKETTSIAL POX R. AKARI MITE MICE
CAT FLEA TYPHUS R. FELIS FLEA CAT/DOGS
4 OTHERS
Q FEVER COXIELLA
BURNETTI
NIL SHEEP/CATTLE/
GOAT
TRENCH FEVER ROCHALIMAEA
QUINTANANA
LOUSE HUMANS
EHRLICHIOSIS EHRLICHIA TICK DEER/DOG
ANAPLASMOSIS A
PHAGOCYTOPH
ILO
TICK DOG/DEER
METHOD OF TRANSMISSION
• NATURAL HOST/RESERVOIR/VECTORS : TICK,
MITE, FLEA, LOUSE
• RESERVOIR HOST : DOGS AND RODENTS
• TRASOVARIAN & TRANSTADEAL
TRANSMISSION
PATHOPHYSIOLOGY
• INNOCULATE INTO DERMIS BY BITE ATTATCH TO
HOST CELL RECEPTORS
• ESCAPE FROM PHAGOSOME BY LYSIS
POLYMERISATION
• ATTACH TO ENDOTHELIAL CELLS OF
MICROVASCULATURE
• CYOKINE MEDIATED DAMAGE TO ENDOTHELIAL
INTEGRITY AND OCCLUSIVE
ENDARTERITIS,MICROINFARCTS “Typhus nodule
of Wolhbach”
CLINICAL APPROACH
FEBRILE SUSPECTED CHILD WITH H/O:
• EXPOSURE TO TICKS/MITE/LOUSE
• TRAVEL TO ENDEMIC AREA
• H/O CONTACT WITH PETS
• CLASSICAL TRIAD: FEVER RASH HEADACHE, ABDOMINAL PAIN
• RASH OVER PALMS AND SOLES
• PALPABLE PURPURA
• NECROTIC RASH
• GANGRENE
• ESCHAR
• LYMPHADENOPATHY
• EDEMA OVER DORSUM OF HANDS AND LEGS
• HEPATOSPLENOMEGALY
• ANEMIA LEUCOCYTOSIS THROMBOCYTOPENIA
• PUO
• FEVER NOT RESPONDING TO ROUTINE ANTIBIOTICS
CASE DEFINITIONS
• SUSPECTED CASE: FEVER MORE THAN 5 DAYS
WITH/WITHOUT ESCHAR ASS WITH RASH
LYMPHADENOPATHY MULTI ORGAN INVOLVEMENT
• PROBABLE CASE: SUSPECTED CASE SHOWING TITERS
1:80 OR ABOVE IN OX2 OX19 OXK ANTIGENS BY WEIL
FELIX TEST OR OPTICAL DENSITY >0.5 IGM BY ELISA
• CONFIRMED CASE: RICETTSIAL DNA DETECTED IN
ESCHAR SAMPLE OR WHOLE BLOOD PCR OR RISING
ANTIBODY TITERS BY 4 FOLDS BY IFA & IPA ELISA
INVESTIGATIONS
• LAB: CBP- LEOCOCYTOSIS
THROMBOCYTOPENIA
• HYPONATREMIA
• HYPOPROTENEMIA
• ELEVATED SERUM AMINOTRANSFERASES
• CSF: MONONUCLEAR PLEOCYTOSIS
WEIL FELIX TEST
• ANTIGENIC CROSS REACTIVITY BETWEEN
RICKETTSIAL SP AND PROTEUS SP
• PROTEUS ANTIGENS OX2 –REACTS WITH SFG
• OX19- TYPHUS GROUP
• OXK- SCRUB TYPHUS
• BY EDMUND WEIL AND ARTHUR FELIX IN 1916
• SENSTIVITY AND SPECIFICITY 49% & 96% .
ELISA FOR IGM ANTIBODIES
• SENSTIVITY 91% AND SPECIFICTY 100%
IMMUNOFLUROSENCE ASSAY FOR IGM AND IGG
• IGM TITERS AFTER 5 DAYS 1:640 SUGGEST
ACUTE INFECTION
• IGG TITES MORE THAN 1:254 SUGGEST ACUTE
INFECTION LESS THAN 1:125 SUGGEST
PREVIOUS INFECTION
IMMUNOPEROXIDASE ASSAY
LATEX AGGLUTINATION TEST
PCR
RGA CLINICAL SCORING
RATHI GOODMAN AGHAI SCORING
CLINAL FEATURES SCORE LABORATORY SCORE
RURAL 1 HB LESS THAN 9 1
PETS 1 PLATELETSLESS THAN
1.5LAKH
1
TICK EXPOSURE 2 CRP>50MG/DL 2
TICK BITE 3 SERUM ALBUMIN
<3GM/DL
1
CONJUNCTIVAL
CONGESTION
2 URINE ALBUMIN >2+ 1
MACULOPAPPULAR RASH 1 SGPT >100 2
PURPURA 2 SODIUM <130MEQ/L 2
PALPABLE PURPUR/
ECHYMOSIS/NECROSIS
3 TOTAL 10
RASH AFTER 48-96 HRS
AFTER FEVER
2
PEDAL ODEMA 2
RASH ON PALMS AND
SOLES
3
HEPATOMEGALY 2
LYMPHADENOPATHY 1
RGA SCORE CUT OFF SCORE 14
• SENSTIVITY 96.15%
• SPECIFICITY 98.84%
• PPV 98%
• NPV 97.7%
• LR+ 82.7%
• LR- 0.04%
HIGH INDEX OF SUSPICION AND CLINICAL
FEATURES AND EPIDEMILOGICAL FEATURES
AND LABAROTORY FINDINGS ARE IMPORTANT
ADJUVANTS IN DIAGNOSIS
TREATMENT
• DOXYCYCLINE : 4.5MG/KG TWO DIVIDED DOSES OR AZITHROMYCIN
10MG/KG FOR 5-7 DAYS
• TERITIARY CARE: Intravenous doxycycline (wherever available)
100mg twice daily in 100 ml normal saline to be administered as
infusion over half an hour initially followed by oral therapy to
complete 7-15 days of therapy.
• Intravenous Azithromycin in the dose of 500mg IV in 250 ml normal
saline over 1 hour once daily for 1-2 days followed by oral therapy
to complete 5 days of therapy OR
• Intravenous chloramphenicol 50-100 mg/kg/d 6 hourly doses to be
administered as infusion over 1 hour initially followed by oral
therapy to complete 7-15 days of therapy
• Doxycycline and/or Chloramphenicol resistant strains have been
seen in South-East Asia. These strains are sensitive to Azithromycin
References
• DHR-ICMR 2016 GUIDELINES
• IAP GUIDELINES 2017
• NELSON Text Book of Pediatrics
• Text Book Of Pediatric Infectious Diseases IAP
THANK YOU

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APPROACH TO RICKETTSIAL INFECTIONS-2.pptx

  • 1. APPROACH TO RICKETTSIAL INFECTIONS DR.K SURENDER ASSOC PROFESSOR DEPARTMENT OF PEDIATRICS KAKATIYA MEDICAL COLLEGE WARANGAL
  • 2. INTRODUCTION • EMERGING INFECTION • EARLY NON SPECIFIC SIGNS AND SYMPTOMS • PROGRESSES WITH FATAL OUTCOMES >30% CASE FATALITY IN UNTREATED OR DELAY • DIAGNOSTIC DIFFICULTIES • BETTER OUTCOME WITH EARLY INITIATION OF TREATMENT
  • 3. ETIOLOGY • MOTILE GRAM NEGATIVE, NON SPORE FORMING, PLEOMORPHIC BACTERIA • OBLIGATE INTRACELLULAR PARASITE • MAJOR ANTIGENS ARE LPS, LIPOPROTEIN, OMP-A, OMP-B • GROWTH IS ENHANCED BY SULPHONAMIDES
  • 4. CLASSIFICATION SNO DISESASE RICKETSIAL AGENT INSECT VECTOR MAMMALIAN RESORVOIR 1 TYPHUS GROUP EPIDEMIC TYPHUS R. PROWAZEKII LOUSE HUMANS MURINE TYPHUS R. TYPHI FLEA RODENT SCRUB TYPHUS R. TSUTSUGAMUS HI MITE RODENT 2 SPOTTED FEVER GROUP RMSF R. RICKETTSII TICK DOG/RODENT INDIAN TICK TYPHUS R. CONORII TICK DOG/RODENT TICK BORNE LYMPHADENOPATHY R. SLOVACA TICK WILD BORE
  • 5. SNO DISESASE RICKETSSIAL AGENT INSECT VECTOR MAMALLIAN AGENT 3 TRANSITIONAL GROUP RICKETTSIAL POX R. AKARI MITE MICE CAT FLEA TYPHUS R. FELIS FLEA CAT/DOGS 4 OTHERS Q FEVER COXIELLA BURNETTI NIL SHEEP/CATTLE/ GOAT TRENCH FEVER ROCHALIMAEA QUINTANANA LOUSE HUMANS EHRLICHIOSIS EHRLICHIA TICK DEER/DOG ANAPLASMOSIS A PHAGOCYTOPH ILO TICK DOG/DEER
  • 6. METHOD OF TRANSMISSION • NATURAL HOST/RESERVOIR/VECTORS : TICK, MITE, FLEA, LOUSE • RESERVOIR HOST : DOGS AND RODENTS • TRASOVARIAN & TRANSTADEAL TRANSMISSION
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  • 9. PATHOPHYSIOLOGY • INNOCULATE INTO DERMIS BY BITE ATTATCH TO HOST CELL RECEPTORS • ESCAPE FROM PHAGOSOME BY LYSIS POLYMERISATION • ATTACH TO ENDOTHELIAL CELLS OF MICROVASCULATURE • CYOKINE MEDIATED DAMAGE TO ENDOTHELIAL INTEGRITY AND OCCLUSIVE ENDARTERITIS,MICROINFARCTS “Typhus nodule of Wolhbach”
  • 10. CLINICAL APPROACH FEBRILE SUSPECTED CHILD WITH H/O: • EXPOSURE TO TICKS/MITE/LOUSE • TRAVEL TO ENDEMIC AREA • H/O CONTACT WITH PETS • CLASSICAL TRIAD: FEVER RASH HEADACHE, ABDOMINAL PAIN • RASH OVER PALMS AND SOLES • PALPABLE PURPURA • NECROTIC RASH • GANGRENE • ESCHAR • LYMPHADENOPATHY • EDEMA OVER DORSUM OF HANDS AND LEGS • HEPATOSPLENOMEGALY • ANEMIA LEUCOCYTOSIS THROMBOCYTOPENIA • PUO • FEVER NOT RESPONDING TO ROUTINE ANTIBIOTICS
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  • 13. CASE DEFINITIONS • SUSPECTED CASE: FEVER MORE THAN 5 DAYS WITH/WITHOUT ESCHAR ASS WITH RASH LYMPHADENOPATHY MULTI ORGAN INVOLVEMENT • PROBABLE CASE: SUSPECTED CASE SHOWING TITERS 1:80 OR ABOVE IN OX2 OX19 OXK ANTIGENS BY WEIL FELIX TEST OR OPTICAL DENSITY >0.5 IGM BY ELISA • CONFIRMED CASE: RICETTSIAL DNA DETECTED IN ESCHAR SAMPLE OR WHOLE BLOOD PCR OR RISING ANTIBODY TITERS BY 4 FOLDS BY IFA & IPA ELISA
  • 14. INVESTIGATIONS • LAB: CBP- LEOCOCYTOSIS THROMBOCYTOPENIA • HYPONATREMIA • HYPOPROTENEMIA • ELEVATED SERUM AMINOTRANSFERASES • CSF: MONONUCLEAR PLEOCYTOSIS
  • 15. WEIL FELIX TEST • ANTIGENIC CROSS REACTIVITY BETWEEN RICKETTSIAL SP AND PROTEUS SP • PROTEUS ANTIGENS OX2 –REACTS WITH SFG • OX19- TYPHUS GROUP • OXK- SCRUB TYPHUS • BY EDMUND WEIL AND ARTHUR FELIX IN 1916 • SENSTIVITY AND SPECIFICITY 49% & 96% .
  • 16. ELISA FOR IGM ANTIBODIES • SENSTIVITY 91% AND SPECIFICTY 100% IMMUNOFLUROSENCE ASSAY FOR IGM AND IGG • IGM TITERS AFTER 5 DAYS 1:640 SUGGEST ACUTE INFECTION • IGG TITES MORE THAN 1:254 SUGGEST ACUTE INFECTION LESS THAN 1:125 SUGGEST PREVIOUS INFECTION IMMUNOPEROXIDASE ASSAY LATEX AGGLUTINATION TEST PCR
  • 17. RGA CLINICAL SCORING RATHI GOODMAN AGHAI SCORING CLINAL FEATURES SCORE LABORATORY SCORE RURAL 1 HB LESS THAN 9 1 PETS 1 PLATELETSLESS THAN 1.5LAKH 1 TICK EXPOSURE 2 CRP>50MG/DL 2 TICK BITE 3 SERUM ALBUMIN <3GM/DL 1 CONJUNCTIVAL CONGESTION 2 URINE ALBUMIN >2+ 1 MACULOPAPPULAR RASH 1 SGPT >100 2 PURPURA 2 SODIUM <130MEQ/L 2 PALPABLE PURPUR/ ECHYMOSIS/NECROSIS 3 TOTAL 10 RASH AFTER 48-96 HRS AFTER FEVER 2 PEDAL ODEMA 2 RASH ON PALMS AND SOLES 3 HEPATOMEGALY 2 LYMPHADENOPATHY 1
  • 18. RGA SCORE CUT OFF SCORE 14 • SENSTIVITY 96.15% • SPECIFICITY 98.84% • PPV 98% • NPV 97.7% • LR+ 82.7% • LR- 0.04% HIGH INDEX OF SUSPICION AND CLINICAL FEATURES AND EPIDEMILOGICAL FEATURES AND LABAROTORY FINDINGS ARE IMPORTANT ADJUVANTS IN DIAGNOSIS
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  • 20. TREATMENT • DOXYCYCLINE : 4.5MG/KG TWO DIVIDED DOSES OR AZITHROMYCIN 10MG/KG FOR 5-7 DAYS • TERITIARY CARE: Intravenous doxycycline (wherever available) 100mg twice daily in 100 ml normal saline to be administered as infusion over half an hour initially followed by oral therapy to complete 7-15 days of therapy. • Intravenous Azithromycin in the dose of 500mg IV in 250 ml normal saline over 1 hour once daily for 1-2 days followed by oral therapy to complete 5 days of therapy OR • Intravenous chloramphenicol 50-100 mg/kg/d 6 hourly doses to be administered as infusion over 1 hour initially followed by oral therapy to complete 7-15 days of therapy • Doxycycline and/or Chloramphenicol resistant strains have been seen in South-East Asia. These strains are sensitive to Azithromycin
  • 21. References • DHR-ICMR 2016 GUIDELINES • IAP GUIDELINES 2017 • NELSON Text Book of Pediatrics • Text Book Of Pediatric Infectious Diseases IAP