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Tropical Infections in ICU:

Tropical Infections in ICU Dr. O.C. Abraham, M.D., M.P.H., Department of Medicine Unit 1 & Infectious Diseases, Christian Medical College, Vellore

Case Presentation:

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

Acute Undifferentiated Febrile Illness:

Acute Undifferentiated Febrile Illness Acute -- <14 days Undifferentiated -- initial symptoms and signs non-contributory Fever -- oral temperature ≥101 0 F

Differential Diagnosis:

Differential Diagnosis Malaria ( P falciparum ) Scrub typhus Leptospirosis Dengue fever

Malaria:

Malaria

Pathophysiology:

Pathophysiology Mechanical microcirculatory obstruction Caused by cytoadherence to the vascular endothelium of parasitized RBC  sequestration & obstruction of small vessels Intra-vascular hemolysis

Clinical Features:

Clinical Features

Severe Malaria:

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

Parasitological Diagnosis:

Parasitological Diagnosis Microscopy Rapid diagnostic tests QBC Antigen detection

Diagnosis: Microscopy:

Diagnosis: Microscopy Low cost High sensitivity & specificity Species identification Quantification

Quantitative Buffy Coat (QBC) Test:

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

Rapid Tests:

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

Treatment:

Treatment Drug of choice: Artesunate* Dose:2.4 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 2005;366(9487):717-25

Scrub Typhus:

Scrub Typhus

Scrub Typhus:

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

Pathophysiology:

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

Clinical Features:

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

Eschar:

Eschar

Sites of Eschar:

Sites of Eschar

Clinical Course:

Clinical Course

Complications:

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

When should scrub typhus be suspected?:

When should scrub typhus be suspected? Undifferentiated febrile illness with: Pathognomonic eschar Evidence of multisystem involvement, especially with: - Transaminase elevation - Thrombocytopenia - Leukocytosis

Lab Diagnosis:

Lab Diagnosis Serology Weil-Felix: poor sensitivity & specificity IFA: ‘gold standard’ ELISA for Ig G & Ig M antibodies (recombinant 56 kd antigen): sensitivity & specificity >90%

Treatment:

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

Leptospirosis:

Leptospirosis

Epidemiology:

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

Clinical Features:

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 (Weil’s disease) Occurs in 5-15% of patients Jaundice Proteinuria, hematuria, oliguria and/or anuria Pulmonary hemorrhages, ARDS Myocarditis

Diagnosis:

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

Biphasic nature of leptospirosis and relevant investigations at different stages of disease :

Biphasic nature of leptospirosis and relevant investigations at different stages of disease Clin Microbiol Rev. 2001 Apr;14(2):296-326

Treatment:

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

Dengue:

Dengue

Dengue Virus:

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

Pathogenesis:

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

Clinical Syndromes:

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

DF: Clinical Characteristics:

DF: Clinical Characteristics Fever Headache Muscle and joint pain Nausea/vomiting Rash Hemorrhagic manifestations NEJM 2005;353:924-932

DHF: Clinical Case Definition :

DHF: Clinical Case Definition Fever, or recent history of acute fever Hemorrhagic manifestations Low platelet count (≤100,000/mm 3 ) Objective evidence of capillary leakage Elevated hematocrit (≥ 20% above baseline) Low albumin Pleural or other serous effusions 4 Necessary Criteria (WHO)

Hemorrhagic Manifestations:

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

DSS: Clinical Case Definition:

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

Distinguishing Dengue & Scrub Typhus:

Distinguishing Dengue & Scrub Typhus Overt bleeding, especially gum bleeds Leukopenia Severe thrombocytopenia Watt G. Am. J. Trop. Med. Hyg.68(5); 2003: 536-538

Diagnosis: Serology:

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

Treatment:

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 2005;353:877-889

Conclusions:

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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