Tropical Infections in ICU

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Tropical Infections in ICU

• Dr. O.C. Abraham, M.D., M.P.H.,
• Department of Medicine Unit 1 Infectious
  Diseases,
• Christian Medical College,
• Vellore

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Case Presentation

• 32-year male
• PC fever x 7 days, jaundice x 3 days, confusion
  x 1 day
• Exam Temp - 105 0F PR 128/min RR 24/min BP
  90/70 mm Hg icteric drowsy, confused
  disoriented hepatomegaly present

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Acute Undifferentiated Febrile Illness

• Acute -- lt14 days
• Undifferentiated -- initial symptoms and signs
  non-contributory
• Fever -- oral temperature 101 0F

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Differential Diagnosis

• Malaria (P falciparum)
• Scrub typhus
• Leptospirosis
• Dengue fever

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Malaria
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Pathophysiology

• Mechanical microcirculatory obstruction
• Caused by cytoadherence to the vascular
  endothelium of parasitized RBC ? sequestration
  obstruction of small vessels
• Intra-vascular hemolysis

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Clinical Features
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Severe Malaria

• Cerebral malaria (unarousable coma not
  attributable to any other cause in a patient with
  falciparum malaria)
• Severe normocytic anemia (lt 5 gm/dl)
• Hypoglycemia
• Metabolic acidosis
• Acute renal failure (S. creatinine gt 3 mg/dl)
• ARDS
• Shock ("algid malaria")
• DIC
• Hemoglobinuria
• Hyperparasitemia (gt5)

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Parasitological Diagnosis

• Microscopy
• Rapid diagnostic tests
• QBC
• Antigen detection

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Diagnosis Microscopy

• Low cost
• High sensitivity specificity
• Species identification
• Quantification

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Quantitative Buffy Coat (QBC) Test

• Staining of the centrifuged compressed red cell
  layer with acridine orange examining under UV
  light source
• Comparison with peripheral smear
• Faster
• More sensitive
• Species identification possible
• Specialized equipment consumables
• Expensive

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Rapid Tests

• Immunochromatographic tests
• Capture of the parasite antigens from the
  peripheral blood using either monoclonal or
  polyclonal antibodies
• Histidine-rich protein 2 of P. falciparum
• Pan-malarial Plasmodium aldolase
• Parasite specific LDH

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Treatment

• Drug of choice Artesunate
• Dose2.4 mg/kg i.v. bolus at admission, 12 H 24
  H followed by 2.4 mg/kg i.v. OD Doxycycline
  100 mg p.o. BID
• Duration 7 days
• Shift to oral drugs as soon as patient is
  conscious can tolerate oral feeds
• Alternative Quinine 20 mg/kg loading dose,
  followed by 10 mg/kg i.v. infusion Q8H
  Doxycycline 100 mg p.o. BID
• Clindamycin in place Doxy in pregnant women
  children

Lancet 2005366(9487)717-25
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Scrub Typhus
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Scrub Typhus

• Etiology O tsutsugamushi
• Three major serotypes - Karp, Gilliam Kato
• Vector chiggers (larva of trombiculid mite)
• Reservoir chiggers rats
• Transovarian transmission
• Normal cycle rat to mite to rat
• Humans are accidentally infected

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Pathophysiology

• No known toxins
• Destruction of cells
• Endothelial injury
• Lympho-histiocytic vasculitis

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Clinical Features

• Incubation period 1 to 3 weeks
• Sudden onset of fever, headache myalgia
• Delirium, nausea, vomiting, cough, jaundice
• Maculopapular rash
• Begins on trunk and spreads to extremities
  (centrifugal spread)
• Eschar

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Eschar
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Sites of Eschar
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Clinical Course
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Complications

• Hepatitis
• Aseptic meningitis / meningoencephalitis
• Thrombocytopenia
• ARDS / Pneumonitis
• Renal failure
• Shock
• Fetal loss

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When should scrub typhus be suspected?

• Undifferentiated febrile illness with
• Pathognomonic eschar
• Evidence of multisystem involvement, especially
  with
• - Transaminase elevation
• - Thrombocytopenia
• - Leukocytosis

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Lab Diagnosis

• Serology
• Weil-Felix poor sensitivity specificity
• IFA gold standard
• ELISA for Ig G Ig M antibodies (recombinant 56
  kd antigen) sensitivity specificity gt90

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Treatment

• Doxycycline 100 mg BD x 7days
• Prompt defervescence
• Therapeutic response as diagnostic test

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Leptospirosis
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Epidemiology

• Etiology L interrogans
• Most widespread zoonosis in the world
• Peak incidence during rainy season
• Occupational recreational exposures
• Source of infection in humans direct or indirect
  contact with the urine of an infected animal
• Portal of entry abrasions or cuts on skin,
  conjunctiva

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Clinical Features

• Biphasic clinical presentation
• Acute or bacteremic phase lasting 1 week
• Immune phase, characterized by antibody
  production and leptospiruria
• Anicteric leptospirosis
• Abrupt onset of fever, chills, headache, myalgia,
  abdominal pain, conjunctival suffusion, transient
  skin rash
• Icteric leptospirosis (Weils disease)
• Occurs in 5-15 of patients
• Jaundice
• Proteinuria, hematuria, oliguria and/or anuria
• Pulmonary hemorrhages, ARDS
• Myocarditis

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Diagnosis

• ? CPK levels
• Culture (blood, CSF, urine)
• Positive serology
• Microscopic Agglutination Test (MAT) (using a
  range of Leptospira strains for antigens that
  should be representative of local strains)
• IgM ELISA

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Biphasic nature of leptospirosis and relevant
investigations at different stages of disease
Clin Microbiol Rev. 2001 Apr14(2)296-326
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Treatment

• Antibiotic therapy
• Shortens fever clearance time, leptospiruria
• Trend towards ? mortality
• Antibiotic regimes
• Penicillin G 1 million U Q4H (iv) x 7 days
• Ceftriaxone 1 Gm OD (iv) x 7 days
• Cefotaxime 1 Gm Q6H (iv) x 7 days
• Doxycycline 100 mg BD (po) x 7 days

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Dengue
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Dengue Virus

• Belongs to the family Flaviviridae
  (single-stranded, non-segmented RNA viruses)
• 4 distinct serotypes (DEN-1, DEN-2, DEN-3,
  DEN-4)
• Principal vector Aedes aegypti

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Pathogenesis

• Secondary infection with another serotype
• Cross-reactive (but non-neutralizing) anti-dengue
  antibodies from previous infection bind to new
  infecting serotype enhance viral uptake of
  monocytes macrophages
• Amplified cascade of cytokines and complement
  activation
• Endothelial dysfunction, platelet destruction,
  consumption of coagulation factors
• Plasma leakage hemorrhagic manifestations

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Clinical Syndromes

• Undifferentiated fever
• Classic dengue fever (DF)
• Dengue hemorrhagic fever (DHF)
• Dengue shock syndrome (DSS)

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DF Clinical Characteristics

• Fever
• Headache
• Muscle and joint pain
• Nausea/vomiting
• Rash
• Hemorrhagic manifestations

NEJM 2005353924-932
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DHF Clinical Case Definition
4 Necessary Criteria (WHO)

• Fever, or recent history of acute fever
• Hemorrhagic manifestations
• Low platelet count (100,000/mm3)
• Objective evidence of capillary leakage
• Elevated hematocrit ( 20 above baseline)
• Low albumin
• Pleural or other serous effusions

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Hemorrhagic Manifestations

• Skin hemorrhages
  petechiae, purpura, ecchymoses
• Gingival bleeding
• Nasal bleeding
• Gastro-intestinal bleeding
  hematemesis, melena, hematochezia
• Hematuria
• Increased menstrual flow

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DSS Clinical Case Definition

• 4 criteria for DHF
• Evidence of circulatory failure manifested
  indirectly by all of the following
• Rapid weak pulse
• Narrow pulse pressure (? 20 mm Hg) OR hypotension
• Cold, clammy skin altered mental status

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Distinguishing Dengue Scrub Typhus

• Overt bleeding, especially gum bleeds
• Leukopenia
• Severe thrombocytopenia

Watt G. Am. J. Trop. Med. Hyg.68(5) 2003
536-538
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Diagnosis Serology

• IgM capture ELISA
• Negative early in the course of the disease
• Should be performed only 4 - 5 days after onset
  of symptoms

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Treatment

• No specific antiviral drug available
• Avoid aspirin, NSAID
• Prompt fluid replacement
• Ringer's lactate as effective as colloids for
  initial resuscitation
• Blood transfusion only with overt bleeding

NEJM 2005353877-889
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Conclusions

• Common features Fever, MODS
• Distinguishing clinical features
• Eschar
• Conjunctival suffusion
• Splenomegaly
• Overt bleeding manifestations
• Lab diagnosis crucial
• Management
• Fluid replacement
• Specific antibiotics

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Thank You!