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A Ht P Ti T Ithf Approach to Patients with Fever

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A Ht P Ti T Ithf Approach to Patients with Fever AhApproach to PtiPatient s with fever Pathogenesis Pathogenเชื้อไวรัส เด็งก่ี สิ่งแวดลอม Hostคน Environmentยุงลาย Pathogen • Bacteria • Virus – AFI : Dengue infection, Chigunkunya virus, acute HIV – Infectious mononucleosis : EBV, CMV, HIV – Fever with rash : Measle, Rubella – Vesicular lesion : HSV, Chicken pox, HZV – Respiratory tract infection : Influenza virus, parainfluenza virus, RSV, adenovirus – Hepatitis : HAV, HBV, HCV – Encephalitis : Enterovirus, HSV, JE • Fungus : PJP, Candida, Cryptococcus • Parasite , Protozoa (Giardia lambia) Host defense system : ระบบการตอตานเชื้อของรางกาย 1.กลไกตอตานเชื้อโดยกําเนิด (Natural or innate defense) หรอกลไกตื อตานเชื้อไม จจาเพาะําเพาะ (non‐specific defense) หรหรอกลไกตอตานเชอทมอยอกลไกตื อต านเชื้อที่มีอยตลอดเวลาู (constitutive defense) 2.กลไกตอตานเชื้อที่เกิดขึ้นจากการปรบตั ัว (Adaptive defense) หรอกลไกตื อตานเชื้อชนดิ จําเพาะ (specific defense) หรอกลไกตื อตานเชื้อที่เกดจากการกระติ ุน (induced defense) Innate defense 1.โครงสรางทางกายวิภาคและสรีรวิทยา 1.1 ผิวหนัง 1.2 เยื่อเมือกบุผิว เชน น้ําตา, mucociliary apparatus ในทางเดินหายใจ, กรดในกระเพาะอาหาร, เชื้อประจาถํ ิ่นในลําไสใหญ 2. การตอบสนองตการตอบสนองตอภอภมูมคิคุมกมกนัน 2.1 เซลลในระบบภ ูมิคุมกัน : phagocyte แบงเปน 2 ชนิดคือ neutrophil และ macrophage 2.2 ระบบคอมพลีเมนต (complement system) มี 3 กลไกคอืื classical pathway, alternative pathway, lectin pathway 2.3 ปฏิกริ ิยาการอกเสบั (inflammatory response )จะเกิด การหลงั่ cytokine หลายชนิด 2.4 การสรางสารอื่น ๆ ที่มีบทบาทตอตานเชื้อ เชน ferritin Adaptive defense • เกเกดหลงจากไดรบเชอเขาสดหลิ งจากไดั ร ับเชื้อเขาสรูรางกายและเกดตามหลงกลไกการตอตานเชอโดยธรรมชาตางกายและเกดตามหลิ ังกลไกการตอตานเชื้อโดยธรรมชาติ เซลล phagocyte ที่จับกินเชื้อแปลกปลอมจะทําการยอยสลายเช ื้อภายในเซลลและนําสวนที่มี คุณสมบัติเปนแอนติเจนออกสผู ิวเซลล จึงเรียกเซลลเม็ดเลอดขาวกลื ุมนวี้ า antigen‐ presenting cell ซึ่งจะรวมตัวในรูปสารเชิงซอนกบสารั major histocompatibility complex (MHC) ซึ่งแบงเปน class I และ class II ซึ่ง antigen presenting cell นี้จะกระตุนระบบภูมิิคุมกนจั ําเพาะได 2 กลไก Adaptive defense 1.Humoral‐mediated response : – การสรางสารน้ํา ไดแก แอนติบอดหรี อื immunoglobulin: Ig ซึ่งแบงเปน IgM, IgG, IgA โดยที่ IgM และ IgG ทําหนาที่ในการตอตานการติดเชื้อในกระแสเลอดและื เนื้อเยอื่ ในขณะท่ี IgA จะถูกหลงออกส่ั บรู ิเวณเยื่อเมอกบื ุผวและทิ ําหนาท่ีชวยปองก ันการบุก รกของเชุ ื้อแปลกปลอมจากภายนอก – การกระตุนระบบคอมพลนระบบคอมพลเมนตีเมนต classical pathway 2. Cell‐mediated response : มักพบในการติดเชื้อกลมุ Intracellular pathogen Approach to Patients with fever Confirm “Fever” •Acute fever < 2 weeks •Prolong fever > 2 weeks • Verification of fever and fever pattern Pattern of Fever Malaria Typhoid Pattern of Fever Pel‐Ebstein pattern BliiBorreliosis (l(relapsi ng fever pattern) Fever patterns are neither sensitive nor specific enough for diagnosis of any disease. (possible exception of tertian and quartan malaria) Cause of Fever • Infectious disease • Non‐infectious disease – CNS: SAH, cerebral infarction/hemorrhage – RS: lung atelectasis, PE – GI: Pancreatitis, Ischemic bowel – Crystal induced arthritis, DVT,Hematoma, Phebitis – Neoplastic fever, Drug fever – Post transfusion, Postoperative fever (<48h) Approach : 1. Sign and Symptom • Fever with specific organ involvement : Pneumonia, UTI • Fever without specific organ involement – Undifferentiated fever – Multi‐organs involvement Approach : 1. Sign and Symptom • Typical manifestation of a common disease • Atypical manifestation of a common disease • Typical manifestation of a uncommon disease • Atypical manifestation of a uncommon disease AhApproach : 2. Host • Infection in the Elderly (>65 year) • Infection in Neutropenia • Infection in Cirrhosis • Infection in Diabetes Mellitus • Infection in Thalassemia patients • Infection in SLE, RA • Infection in Transplant recipients Approach : 2. Host • Fever in HIV infected patients • Fever in ICU • Fever in the returned traveler • Postoperative fever • Fever of unknown origin Approach : 3. Epidemiology, Exposure •Race • Domicile, Region • Career • Hobby • Immunization •Travel Approach : Fever from Infectious disease 1. Sign & Symptoms – Specific organ syypmptom –Non specific organ symptoms : Undifferentiated / Multi‐organ involvement 2. Host 3. Epidemiology, Exposure Acute Undifferentiated Fever Case 1 • 30 year old healthy woman • CC: High fever with chill for 3 days •PI: 3 days PTA, High fever with chill, headache, muscle pain, diarrhea?(1‐2 times/d), no dysuria, no cough, no abnormal bleeding •PE: BT 38.5C BP 120/80 mmHg, PR 100 bpm, RR 18 /min, no stiffness of neck, others: WNL • Q&A: Acute Undifferentiated Fever Acute systemic febrile illness, or AtAcute PUO, or StSystemi c ifinfec tion Acute Fever ‐ No primary focus of infection ‐ Multi‐system involvement Acute Undifferentiated Fever (Systemic Febrile Illness) Primary Bacteremia Dengue Malaria: Infection Rickettsioses: Pf, Pv, Po, (Acute viral hepatitis, SbScrub thtyphus, Pm, Chikungunya, Acute Leptospirosis Typhus group, retroviral syndrome Spotted fever group P.knowlesi Infectious mononucleosis Approach to Patients with fever • Confirm “Fever” • S/S : Undifferentiated fever •Host: Healthy • Epidemiology, Exposure : Race, Domicile, Career, Hobby, Immunization, Travel, Incubation period •Investigation for diagnosis Sign & Symptoms Malaria‐ Sign & Symptoms Asexua l deve l opme nt (Schizogony) •30 mins • Exoerythrocytic cycle (5‐16 dayy)s) • Erythrocytic cycle (48‐72 h) • Schizogony(merozoites) • gametocytogenesis (gametocyte) Sexual development (Sporogony) Viral Infection • Dengue infection: Dengue fever, Dengue Hemorrhagic fever • Viral hemorrhagic fever: Hanta virus • Chikunggyunya infection • Infectious mononucleosis : EBV, CMV Bacteremia Pathogenic Leptospira High fever spp. HdhHeadche O. tsutsugamushi, R. Conjunctival injection typhi Myalgia etc. Meningoencephalitis Jaundice, Abnormal LFT Hemoptysis, Pneumonitis Oliguria, renal failure Myocarditis etc. Clinical presentations: Leptospirosis and Rickettsioses •Latent or subclinical infection • Acute uncomplicated or flu‐like febrile illness • Acute fever plus –hepatic dysfunction‐‐> acute acalculous cholecystitis – renal dysfunction‐‐> acute renal failure – interstitial pneumonitis ‐‐‐> lung hemorrhage‐‐> ARDS – aseptic meningoencephalitis – multiorgan dysfunction – hhihemorrhagic manifes ta tions Acute Undifferentiated Fever • 1,663 adltdult patien ts presenting with AtAcute fever, withou t an obvious focus of infection, at 6 hospitals in Thailand • between October 2000‐ March 2003 – Leptospirosis 463 (27.8%) – Scrub typhus 268 (16.1%) –Murine typhus 28 (1.7%) – Leptospirosis and rickettsioses 82 (4.9%) – Spotted fever group rickettsioses 18 (1.1%) –Dengue infection 55 (3.3%) – Bacteremia 8 (0.5%) – Unknown 725 (43.6%) Anicteric Leptospirosis Icteric Leptospirosis Weil’s Syndrome ระยะแรก ระยะที่สอง ระยะแรก ระยะท่ีสอง 3-7 วัน 0-30 วัน 3-7 วัน 10-30 วัน SeptSepticemicicemic Immune Septicemic Immune อาการไข Myalgia Meningitis Jaundice Headache Uveitis Hemorrhage Abdominal Rash Renal failure pain Fever Myocarditis Vomiting Conjunctival suffusion Fever Blood Blood CSF CSF Urin Urin e e CLINICAL PRESENTATIONS OF 540 PATIENTS WITH SUSPECTED SEVERE LEPTOSPIROSIS Clinical Presentations N (%) ‐ Acute febrile illness 127 (23.5) ‐ Jaundice 154 (28.5) ‐ Renal dysfunction 182 (33.7) ‐ Lung involvement 111 (20.6) ‐ Hypotension 72 (13.3) ‐ Bldileeding complicati on 63 ()(11.7) ‐ Thrombocytopenia (<100,000) 189 (35.0) Clinical Infectious Diseases, 20042004;; 3939:: 1417‐24 CLINICAL PRESENTATIONS OF 540 PATIENTS WITH SUSPECTED SEVERE LEPTOSPIROSIS : FINAL DIAGNOSIS Diagnos is N (%) Leptospirosis Only 256 (47.4) Plus rickettsioses 62 (()11.5) Plus other bacteremia Rickettsioses 2 (0.04) Others 71 (()13.1) Other bacterial infection Viral infection 22 (0.4) Unknown 19 (0.3) 88 (16.3) Clinical Infectious Diseases, 2004; 39: 1417‐24 Rickettsioses‐ Sign & Symptoms • Sepsis study at Maharat Nakhon Ratchasima Hospital • Between November 2001 to January 2002 • 18/51 (35.3%) of community‐acquired sepsis were caused by scrub typhus. •3 (16.7%) patients died Thap LC, et al. Southeast Asian J Trop Med Public Health 2002 Case 1 : AFI • อาชอาชพีพ: พนพนกงานขายหางโลตสกงานขายหั างโลตัส • ภูมิลําเนา :พักอยบู านหลังโลตัส รอบบานมีสวนขนาดเล็ก ไมมี สสตวเลยงัตวเลี้ยง • โสด ปฏิเสธประวัติมีเพศสัมพันธ ประจําเดือนมาปกต ิ LMP 20/09/54 • เดินทาง : 3 อาทตยิ กอนเด นทางไปเชิ ียงใหมอยูแตในเม องื ไมไดเขาปา ไปเชาเยนกล็ ับ ไมมีคนละแวกบานเปน ไขเลือดออก • วัคซนี : ไมเคยฉีดวัคซนปี องกันไขหวัดใหญ • งานอดิเรก : อานหนังสือ Investigation Case 1 : AFI‐ Initial investigation • CBC • Urinary analysis • Hemoculture ? • Bun/Cr, LFT •CXR ? Malaria‐ Investigation for Diagnosis • Uncomplicated malaria ‐ P. falciparum ‐ P. vivax ‐ P. ovale ‐ P. malariae ‐ P. knowlesi • Complicated or severe malaria ‐ P. flifalciparum ‐ P. vivax ‐ P. knowlesi Malaria‐ Investigation for Diagnosis • Microscopy : "gold standard” –Thick smears are used for screening purposes‐ low parasitem ia –Thin smears are for morphological detail and species identification •Rapid diagnostic tests (RDT) • Molecular technique ; especially for differentiate betaween P.m. & P.knowlesi Malaria‐ Investigation for Diagnosis Parameter Microscopy PCR Fluorescence Dipstick Dipstick HRP-2 pLDH, Sensitivity 5-10 5 50 >100 >100 parasites/µl) PfP. f PfP. f only PfP. f and PvP. v Specificity All species All species good, others good difficult Parasite density Yes No No Crude Crude or estimation estimation parasitemia Time f or 30–60 m in 24 h 30–60 m in 20 m in 20 m in result Skill level High High Moderate Low Low Equipment Microscope
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