Dengue

Chapter 1 – Dengue

v History

· History of being @ Dengue endemic area.

· Incubation period  3-14 days.

· (Many, prodrome, sensitive & specific indicator, ~ for 2-3 days) chill, erythemato’ skin’s mottling, facial flush.

· Child < 15 y.old usu’ (+) nonspecific febrile syndr’ ~ + maculopapul’ rash.

· Classic dengue begins w/ sudden fever’s onset, chills, severe (term: ‘breakbone’) ache @ head, back, & extremities, + other sympt’.

· Fever lasts 2-7 days & ~ reach 41^OC (if lasts > 10 days, ~ Ø due to Dengue).

· Other sympt’: Headache, Retroorbit’ pain, Generalized pain (arthralg’, myalgia), Nausea, Emesis, & (rare) diarrhea, Rash, Weakn’, Altered gustatory, Anorexia, Sore throat, Mild hemorrhag’ manifest’ (eg: petechia, gum bleed’, epistaxis, ecchymoses, menorrhag’, hematuria), Lymphadenopathy.

· The rash (typic’ onset @ day 3, lasts for 2-3 days): Maculopapul’ or macular confluent @ face, thorax, @ flexor surfaces, w/ skin-sparing islands.

· Fever (typic’) ↓ w/ ↓ed viremia.

Ocassional’, more @ child: fever ↓ed for 1 day & then returns (‘saddleback’ fever)

· Second Rash (onset ~ @ 1-2 days of defervescen’, lasts for 1-5 days): morbiliform, maculopapul’, Ø @ sole and palm, ocassional’ desquam’.

· Slow & complete recovery, fatig’ & exhaust’ ~ persist after fever subsided. Convalesc’ phase ~ lasts 2 weeks.

· Risk of Dengue Hemorrhag’ Fever (DHF) or Dengue Shock Syndr’ onset @ Deverfescen’.

DHF Presaging: Abdomin’ pain + restlessness, mental status change, hypotherm’, ↓ed platelet count.

· DHF’s 90% cases @ < 15 y.old.

Initial: similar to dengue fever & other febrile viral ill’. (W/in 24 hours pre- to a bit after fever breaks) (+) Plasma leakage’s signs, + (+) hemorrhag’ sympt’ s.as bleeding @ trauma & GI, & hematuria. Px ~ present w/ abdomin’ pain, emesis, febrile seizures (@ child), & ↓ed consciousn’.

If untreated (most likely) à Dengue Shock Syndr’. (Common sympt’ of impending shock) Abdomin’ pain, emesis, & restless’, ~ + circulato’ fail’.

() Sympt’ onset after > 2 weeks since left Dengue endemic area ~ Ø Dengue.

v Physic’ Exam’

· Acute Febrile Ill’ + 1 of:

o  +++ & generalized headache.

o  Initial febrile phase lasts 3-4 days, then remission of few hours to few days.

o  Retroorbitalgia.

o  +++ myalgia, espec’ @ lumbar & extremit’.

o  Arthralgia usu @ knee & shoulder.

o  Rash @ 80% cases set on during fever remission.

Characteris’ start on hand & feet’s dorsum spread to arms, legs, torso, & (rare) face.

Lasts 2 hours – several days.

Before (+) rash, hard to distinguish w/ yellow fever, malaria, & influenza.

o  Hemorrhag’ manifest’.

o  Leukopenia.

o  Depression

· ~ +:

o  Injected conjunctiva.

o  Facial flush’ (sensitive & spec’ predictor of dengue)

o  Inflamed pharynx

o  Lymphadenopathy

o  Nausea & emesis

o  Dry cough

o  Tachycardia, bradycardia, and conduction defects.

· (50% cases) Px w/ characteris’ rash (~ maculopapul, scarlatiniform, petechial, or macul’).

· Hemorrhag’ manifest’ also: (most common)petechia & bleed’ @ venipunct’ site; petechia, nasal or gum bleed’, melena, hematemes’, & menorrhag’.

· Usu’ (+) Torniquet Test:

o  Inflate bloodpress’ cuff @ upper arm to between systole & diastole pressu’ for 5 minutes.

o  Then, if @ area under pressu’ ≥ 3 petechia/cm² or 20 petechia/inch² à (+).

· (Rare) Seizure, & encephalopathy w/o typical dengue sympt’.

· Neurol’ complic’: neuropathy, Guillan-Barre syndr’, transverse myelit’.

· @ Dengue Hemorrhagic Fever

o  Similar to Dengue Fever, include: biphasic fever curve, hemorrhag’ manifest’ > Dengue Fever’s, signs of peritoneal- & or pleur’-effusion.

o  Minimal diagnostic criteria:

· Fever

· Hemorrhag’ manifest’ (eg.: hemoconcentration, thrombocytopenia, Torniquet Test (+)).

· Circulat’ fail’, s.as: signs of vascul’ permeabil’ (eg: hypoproteinemia, effusion).

· Hepatomegaly.

o  (30% cases) Injection Conjunctiva.

o  Optic Neuropathy –(ocassional’)à permanent & +++ visual impair’.

o  Generalized lymphadenopathy.

o  (97% cases) Pharyngeal Injection.

o  Hepatomega’ more often @ Dengue Shock Syndr’.

o  Hepatic Transaminase ↑ ~ mild – moderate.

o  (Rare, Complic’) Encephalopathy ~ result from combinat’ of hyponatremia, hepatic injury, anoxia, cerebr’ edema, & intracrani’ hemorrhage.

· @ Dengue Shock Syndr’

o  Hypotension

o  Brady♥ (paradoxical) or tachy♥ related to hypovolem’ shock.

o  Hepatomega’

o  Hypotherm’

o  Narrow Pulse Pressu’

o  Signs of ↓ed Peripher’ Perfus’.

v Differ’ Diagnos’

() (Rare) Vertical transmission (mother (w/ dengue @ peripartum) to neonate) à Neonate should be evaluated for dengue w/ platelet count & serologic studies.

· Pregnancy Preeclampsia

o  Overlap’ sympt’: thrombocytopenia, liver dysfunct’, capillary leak, ascites, ↓ed uria. Definitive diagnosis via serology testing.

· Viral Hemorrhagic Fevers

· Malaria

· Yellow fever

· Rift Valley fever

· St. Louis encephalitis

· Influenza

· Mayaro fever

· Ross River fever

· Sindbis virus

· Ebola virus

· River Virus

· Chikungunya Orbivirus

· West Nile encephalitis

· Roseola infantum

· Scarlet fever

· Idiopathic thrombocytopenic purpura

· Arenaviruses

· Leptospirosis

· Meningitis

· Rickettsial Infection

o  Typhus (eg: Scrub Typhus)

o  Spotted Fever (eg: Rocky Mountain Spotted Fever)

· Viral Hepatitis

v Workup

· Lab criter’ for diagn’ needs 1 or more of:

o  Dengue virus isolat’ from serum, plasma, WBC, or autopsy sample.

o  Demonstrated ≥ 4x change in reciprocal IgG or IgM titer to ≥ 1 dengue virus in paired serum samples.

o  Demonstrated dengue verus Antigen in autopsy sample via immunohistochem’ or immunofluoresc’ or in serum sample via enzyme immuno assay (EIA).

o  Detected viral genomic sequences in autopsy, serum, or CSFluid samples via PCR.

· (14 Mar 2014, current’ only @ research lab) RT-PCR for rapid & serotype-specif’ diagn’.

· Should also (+) tests:

o  Complete Blood Count

o  Metabolic Panel

o  Serum protein & albumin level

o  Liver panel

o  Disseminated Intravascular Coagulation (DIC) panel

· Guaiac test should be performed on suspected Dengue Px, due to subtle early coagulopathy signs.

· Typing & Crossmatching Blood should be done @ severe DHF or Dengue Shock Syndr’ because blood products ~ needed.

· Urinalysis looks for hematuria.

· Culture of blood, urine, CSFluid, & other body fluid should be done as needed to find Px’s condition’s etio’.

· Arterial blood gas should be assessed in severe cases to know pH, O₂ation, & ventilat’.

· ECG ~ demonstrate Øspecif’ changes due to fever, electrolyte disturban’, tachy♥, or medicat’.

Unclear usefuln’ in looking for ♥ involvem’s markers.

· Skin lesion biopsy @ nonfatal, uncomplic’ Dengue shows abnormal @ blood vessels.

· Skin lesion biopsy (primary finding): Endothelial swell’, perivascul’ edema, MN cell infiltration.

· Chest radiography to look for pleural effus’ (typic’: right-sided) & bronchopneumon’.

· (Common) Bilateral pleural effus’ @ Dengue Shock Syndr’.

· Head CT w/o contrast ~ done @ altered mental status to look for intracran’ bleed’ or cerebr’ edema from DHF.

· Complete Blood Count

o  (Observed near end of febrile phase, more +++ > other febrile ill’ in dengue-epidemic area) Leukopenia, neutropenia, thrombocytopenia (characterist’ < 100,000 platelet/μL, 50% cases), oft’ + lymphopenia.

o  Lymphocytosis, w/ atypic’ lymphocyt’, commonly (+) pre- defervescen’ or shock.

o  Hematocrit: ↑ > 20% (due to plasma extravasat’ & or 3rd space fluid loss) à sign of hemoconcentration, precedes shock.

Should be monitored every ≤ 24 hours to helf early-find DHF; every 3-4 hours in severe DHF or Dengue Shock Syndr’.

o  Thrombocytopenia (< 100,000 platelet/μL) @ DHF or Dengue Shock Sydnr’ precede defervescen’ & shock’s onset. Platelet count should be monitored every ≤ 24 hours to early-find DHF.

· Metabolic Panel & Liver Enzymes

o  (Most common electroly’ abnorm’ @ DHF or Dengue Shock Syndr’) Hyponatremia.

o  (@ Px w/ Shock) ↑ed BUNitrogen, & (must be corrected quick’) Metabolic acidosis.

o  (Uncommon) Acute renal injury.

o  Mild’ ↑ed transaminase levels to several kilo @ DHF w/ Acute hepatit’.

o  Hypoalbuminem’s sign of hemoconcentrat’.

· Coagulation studies

o  ~ help guide therapy in Px w/ severe hemorrhag’ manifest’.

o  Findings:

· Prolonged prothrombin time.

· Prolonged activated partial thromboplastin time.

· Low fibrinogen & ↑ed fibrin degradat’ product levels’re signs of DIC.

· Serum studies

o  For serodiagnosis (basis: ↑ed antibody titer @ paired specim’ taken during acute stage & convalesc’ phase), PCR, & virus isolati’.

o  Results vary depend' on whether it’s 1stary or 2ndary infec’.

o  IgM capture enzyme-linked immunosorbent assay (MAC-ELISA)’s most widely used for dengue’s serologic assay.

o  Other tests:

· Complement Fixation (CF)

· Neutralization Test (NT)

· Hemagglutination Inhibition (HI)

· IgG ELISA

· NS1 Strip Test

o  Take serum sample (then immediat’ put on white ice & send to lab) a.s.a.possib’ after ill’s onset & after death or discharge from hospital.

Then, take 2nd serum sample (for convalescent-phase serolog’ test’) 7 – 21 (ideal: 10) days after acute serum sample.

o  1 positive PanBio- IgG or IgM’s high rate of false positive & should be confirmed using via more sensitive diagn’ test, otherwise, platelet & WBC count can be helpful (thrombocytopenia & leukopenia (+) @ 40.4% confirmed cases, 6.1% false positive cases).

· USG

o  Potential’ timely, cost-effective, easily-used in evaluati’ potential DHF.

o  Positive & reliable findings: fluid in chest & abdomin’ caviti’, pericard’ effus’, & (~ presages clinical’ signific’ vascul’ permeabi’) thicken’ gallbladder wall.

o  Daily chest & abdomin’ USG’s useful @ evaluati’ Px w/ suspected DHF.

o  (Some) Plasma leakage’s detected w/in 3 days of fever onset (most common: pleural effus’).

o  (Some) Predicted DHF @ Pxs before (+) hemoconcentration’s criteria.

· Case Definitions

o  Suspected Dengue = compatible w/ clinical description.

o  Probable Dengue = Suspected Dengue + ≥ 1 of these:

· Supportive serology (reciprocal HI antibody titer > 1280, comparable IgG EIA titer, or positive IgM antibody test @ late acute or convalsesc’ phase serum sample).

· Occur @ same time & place as other confirmed dengue cases.

o  Confirmed Dengue = Suspected Dengue + Lab’s confirmation.

o  DHF’s Diagnos’ Criteria: probable- or confirmed-case of Dengue & hemorrhag’ tendenc’ signed by:

· (Positive) Torniquet Test

· Petechia, Ecchymoses, or Purpura.

· Bleed’ of mucosal, GI, injection sites, or other.

· Hematemesis or melena & Thrombocytopenia (< 100,000 cells/μL).

· Evident’ Plasma Leakage due to ↑ed vascul’ permeabil’.

o  Plasma leakage manifest’:

· > 20% ↑ in average hematocrit level for age & sex.

· >20% ↓ in hematocrit following volume replacement compared w/ baseline.

· Plasma leakage’s signs (eg: pleural effus’, ascites, hypoproteinem’).

o  (+) Dengue Shock Syndr’ Diagnosis = DHF + evident circulat’ fail’ s.as:

· Rapid, weak pulse

· Narrow pulse pressu’ (< 20mmHg), w/ ↑ed peripher’ vascul’ resistan’ (PVR) & ↑ed diastol’ pressu’.

· Hypotension

· Cool, clammy skin

· Altered mental status, although Px’s initial’ alert.

o  Shock onset ~ subtle, signed by: ↑ed diastol’ pressu’ & ↑ed PVR in alert Px.

Reference:

1. http://emedicine.medscape.com/article/215840-clinical
2. http://emedicine.medscape.com/article/215840-differential
3. http://emedicine.medscape.com/article/215840-workup