2012.05.26

Arbovirus

Arbovirus in Taiwan

24242424

Chief Complaintfever and general malaise for 4 daysThis 15-year-old girl has no significant past medical history. She went to Cambodia on 8/10~8/17 with her church group for a mission trip. After coming back, she started to have mild fever with temperature of 37.5~38.0 degrees. The fever was accompanied by rhinorrhea and a mild cough with sputum.

Present Illness

ER Initial Evaluation 8/21Influenza rapid test: negative

Hb: 13.1 g/dL Ht: 38.8%WBC: 1300 mL ANC: 728DC: (0-56-0-0-16-28)PLT: 43103/mLCRP: 0.57 mg/dL

8/23 CBC, WBC/DC, ChemistriesHb: 14.7 g/dL Hct: 43.3% (11%)Reticulocyte: 1/1000 RBCsWBC: 1300 mL DC: (2-37-0-0-11-47-Atypical-Lym: 3)PLT:19103/mLANC: 507ASL(GOT):200 U/LALT(GPT):59 U/L LDH: 501 IU/L

8/25

8/27

255000

2010

Trends in reported number of dengue cases and CFR reported from countries of the SEA region, 1985-2009WHO: comprehensive guidelines for prevention & control of dengue & DHF, 2011

2005-201120025336 ( )

2006-2011: :

1234

3~8 (: 14)

1 ~ 5

Aedes aegypti : Nervous feeder : bite > 1 host to complete one blood meal Need more than 1 feed to complete the gonotropic cycle multiple cases

Aedes albopictus :

50-90% () (DHF) (DSS)

The course of dengue illnessFebrile phase Dehydration; high fever may cause neurological disturbances and febrile seizures in young childrenCritical phase Shock from plasma leakage; severe hemorrhage; organ impairmentRecovery phase Hypervolemia (only if intravenous fluid therapy has been excessive and/or has extended into this period)

WHO: comprehensive guidelines for prevention & control of dengue & DHF, 2011DHF DF + bleeding

WHO classification & gradingWHO: comprehensive guidelines for prevention & control of dengue & DHF, 2011

WHODHF/DSSDHF:

Suggested dengue case classification and levels of severity

Unusual or atypical manifestations of dengueWHO: comprehensive guidelines for prevention & control of dengue & DHF, 2011

Unusual or atypical manifestations of dengueWHO: comprehensive guidelines for prevention & control of dengue & DHF, 2011

3812 394036

3 ~6()

-

: :

(): : 20% (): 20%3gm/dl

: (2.5) petechiae : (2.5x2.5=6.25)20 petechiae (tourniquet test)

Hct: 39, PLT 22K, WBC 6400/uL, GOT 329, GPT 256Hct: 35.5, PLT 35K, WBC 4600/uL, plasma reabsorptionDay 6 Day 9

: DSS

20 mmHg)

12 -

shock Shock: D5 or D6: fluid reabsorptionfluid overload

Warning Signs for Dengue Shock

When Patients Develop DSS: 3 to 6 days after onset of symptoms

Initial Warning Signals: Disappearance of fever Drop in platelets Increase in hematocrit

Alarm Signals: Severe abdominal pain Prolonged vomiting Abrupt change from fever to hypothermia Change in level of consciousness (irritability or somnolence)

Four Criteria for DHF: Fever Hemorrhagic manifestations Excessive capillary permeability 100,000/mm3 platelets

: (PMN) CBC

102018 42%45%50%

- WBC3 5 RBCPLTGPTA/G

DHF

WHO (aspirinNSAID)dengue aspegic (Stin)

Group A patients who may be sent homeAble to tolerate adequate volumes of oral fluids and pass urine, no warning signsManagement Encourage oral intakeGive paracetamol for high fever instead of acetylsalicylic acid (aspirin), Ibuprofen or other NSAIDsInstruct the care-givers of warning signs monitored daily

Warning signsPersistent vomiting, not drinking.Severe abdominal pain.Lethargy and/or restlessness, sudden behavioral changes.Bleeding: Epistaxis, black stool, hematemesis, excessive menstrual bleeding, dark coloured urine (hemoglobinuria) or hematuria.Giddiness.Pale, cold and clammy hands and feet.Less/no urine output for 46 hours.

Group B patients who should be referred for in-hospital managementCriteria Warning signsCo-existing conditions such as pregnancy, infancy, old age, obesity, diabetes mellitus, renal failure, chronic hemolytic diseasescertain social circumstances (such as living alone, or living far from a health facility without reliable means of transport)

- : 3-4

: 32

+ :

:

: : 30 :6 2 4 ::

- (Ringers lactate) (Ringers acetate)51:2 1:1 40dextran 40

Algorithm for fluid management in compensated shock

Fluid management in hypotensive shock

Volume replacement flow chart for patients with DSS*

48 IV fluid

(DIC)

20,000/ul : < 20,000/ul DIC 20,000/ul APTT < 20,000/ul

: :

:

24 2 > 50,000/ul: 1-2traumatic activities: 3-5

WHO: comprehensive guidelines for prevention & control of dengue & DHF, 2011

+ HctPLT >10Hct PLT 10*DHF*: DHFDHF

: infants and the elderlyobesitypregnant womenpeptic ulcer diseasewomen who have menstruation or abnormal vaginal bleedinghemolytic diseases, e.g. G-6PD deficiencythalassemia and other hemoglobinopathiescongenital heart diseasechronic diseases such as DM, HTN, asthma, ischemic heart dzchronic renal failure, liver cirrhosispatients on steroid or NSAID treatment

WHO: comprehensive guidelines for prevention & control of dengue & DHF, 2011

Description of demographics and clinical manifestations of fatal patients 10 fatality (8 M and 2 F; median age, 63.5 years) with DHF (7 grade II DHF and 3 DSS) a dengue-related mortality rate of 1.3%. Of these 10 fatal patients, the time lapses between onset and hospital presentation ranged from 1 to 6 days (median, 2 days) hospital presentation to fatality 2 to 18 days (median, 4.5 days)onset to fatality 4 to 21 days (median, 7.5 days) 9 was sampled for dengue diagnosis within 24 h after admission median from dengue onset to the definitive diagnosis was 5 days (range, 411 days)

Causes of fatalitiesintractable GI bleeding with hypovolemic shock: 4 DSS alone : 2 DSS with SAH K. P bacteremia and meningitis with septic shock sepsis due to VAP concurrent E. faecalis bacteremia +massive GI bleeding

2011DHF 4GI bleeding 3shock, 1OHCA , DHF

CaseAgeOnsetReport as DHF ExpireUnderlying diseaseDHF symptom1608/278/318/31DMHTNLGI bleeding26610/2410/2410/24DMHTNUGI & LGI bleedingshock36911/311/811/7DMHTN cirrhosisUGI & LGI bleedingshock46410/1610/2410/23HTN ESRDgoutUGI & LGI bleedingshock54812/612/1712/17DMHTN ESRD hyperlipidemia CADUGI & LGI bleedingshock AMI

Case 1 64 y/o M went to ER at 4AM, 2011/10/16 because of fever / bone pain since yesterday Lived in CKD, gout Hx At ER T/P/R=38/83/19, BP=138/86 lab: Hb=9.7, PLT=121K, WBC: WNL, Seg=78%, Cr=7.3 Keto 1amp, N/S250ml MBD (11AM): URI/pharyngitis: panadal, keflex, peace x 3 days

Revisit ER on 10/19 7AM (D5)DOE and chest discomfort for 2 days T/P/R=37.4/103/24, BP=116/94 Muscle soreness(+), deny URI symptoms or skin rash , low grade fever (+), abdominal pain (+) Lab : WBC=7.5K, Hb=15, PLT=37K, GPT=73,BUN/Cr=121/10, ABG=7.322/22/63/11.3, INR=1.15, aPTT=39.4 sAdmission at 11AM, BW=78Kg , IBW=60 Dengue: only NS1(+) Abd echo: acites (+), CXR: bil lower lung infiltrate (+), cardiomegaly(+) Tentative diagnosis : dengue fever+ thrombocytopenia, acute on CKD

Few Bloody stool noted at 3PM, 10/20 Increase IVF =1000ml/day, and suspect DHF Worsening dyspnea on 4 : 30PM , plan to transfer to ICU Transfer to KMUH T/P/R=36/64/22, BP=91/42

Case 2 60 y/o male, visit ER by 119 at 8:30 AM, 2011/8/31 because of SOB, nasal and anal bleeding this morning Lived in , wife and daughter had dengue Had fever for 4 days s/p LMD tx DM, HCVD Hx At ER T/P/R=37.8/138/30, BP=116/76mmHg, E4V5M6 08:35 profuse bleeding in mouth 08:47 CPR Lab : WBC=9.2K, N/L=77/19, Hb=17.8, Hct=51.5%, PLT=20K Cr=1.6,AST/ALT=176/73, sugar=330, HbA1C=10.3, Transfer to ICU, repeated CPR, AAD at 11:50AM

Case 370 y/o male, visit ER at 7PM, 2011/11/5 because of fever x 3 days, anorexia, tarry stool Lived in HTN, DM (+) At ER (D3) T/P/R, 36.9 /103/20, BP=161/103 mmHg, Lab : WBC =5.61K, Hb=16.6 gm/dl, Hct=49.4%, PLT=44K,BUN/Cre=25/1.1, ALT=115 MBD at 11PM, Dx : fever, cause? r/o UGIB , thrombocytopenia

Revisit ERRevisit ER at 7PM the next day (D4) because of general weakness, At ER (11/6) T/P/R=36.8 /137/20, BP=92/65mmHg, consciousness clear Lab : WBC=6.14K, Hb=14.4 gm/dl, Hct=43.4%, PLT=16K, ALT/AST=242/353, Bun/Cre=36/1.3, Glu=418, CRP=1.7, s/p PLT B/T, arrange PES

At ER (11/7) 5AM: BT=38 , tarry stool, BP=93/63mmHg, 6AM: WBC=7.67K, Hb=10.7, Hct=32.2, PLT=17K, s/p PRBC, PLT, FFP B/T 12 AM: SBP=40, s/p endo intubation ,r/o UGIB related 4 PM: skin rash seen, notify dengue 9 PM: AAD

Case 4 48 y/o female, went to ER by 119 at 7PM, 2011/12/08 because of general malaise, fever for 2 days Lived in DM, HTN, CAD (+) ESRD under H/D At ER T/P/R=37.8/88/16, BP=166/89, Lab : WBC=4.9K, Hct=34.7%, PLT=97K, AST/ALT=454/256 Notify dengue on 12/11, and stayed at ER till 12/13

At ward 12/15 : T/P/R=37.1/80/20, BP=80/55mmHg, At night tarry stool (+), consciousness disturbed Lab: WBC=11.3K, Hct=31.3%, PLT=158K, AST/ALT=51/42 12/16: WBC=22.1K, Hct=40.5%, PLT=256K, sudden collapse s/p CPR, At ICU added tazocin, profound shock (+) died on 12/17

Lesson learned Reducing dengue mortality requires an organized process that guarantees early recognition of the disease, and its management and referral when necessaryWhen major bleeding does occur, it is always associated with Profound shock ThrombocytopeniaHypoxia and acidosisMultiple organ failure Disseminated intravascular coagulation

Severe dengue should be consideredPatient from an area of dengue risk with fever of 27 days plus any of the following features:Evidence of plasma leakage, such as:high or progressively rising haematocrit;pleural effusions or ascites;circulatory compromise or shockSignificant bleedingAltered level of consciousnessSevere gastrointestinal.Severe organ impairment

Criteria for transfer early presentation with shock (on days 2 or 3 of illness);severe plasma leakage and/or shock;undetectable pulse and blood pressure;severe bleeding;fluid overload;organ impairment (such as hepatic damage, cardiomyopathy, encephalopathy, encephalitis and other unusual complications).

: xxxx /--- :Tourniquet test: / ----: http://www.cdc.gov.tw/public/Attachment/1419149271.pdf

2006/02/05: >15 200

1952 Chikungunya

& :

: 212 37

: 2 5

:

Source: Guerrant et al., Tropical infectious diseases. 2ed. 2006

http://www.cdc.gov/ncidod/dvbid/chikungunya/CH_GlobalMap.html

Chikungunya (CHIKV) &: Central/East African type

High prevalence rate (90%) for CHIKV among people aged > 40 y/o in Taiwan 40 years agoLow prevalence rate (

2009: 4/17- 4/2012 y/o4/22: fever up to 39.80C, vomiting, headache4/23: arthralgia, skin rash4/24: fever subsidedLab: PCR: CHIKV (+), Dengue-2 (+)Dengue IgM & IgG ; CHIKV IgM & IgG

10 y/o 4/24: fever4/25: headache, muscle pain, abdominal pain4/27: fever subsidedLab: PCR: dengue-2 (+); Dengue IgM & IgG

3 2010/3/17 3& :

2005-2011

2005-2011 !

2005-2011

Most: asymptomaticFever: Varies from low grade to high gradeLasting for 24-48 hoursDeath: rare, most in patients with underlying disease

WHO: Guidelines on clinical management of chikungunya fever, 200850% ( 2 days)25%15%20%5%

Joint painWorse in the morning, relieved by mild exercise, exacerbated by aggressive movementsMay remit for 2-3 days, then reappear in a saddle back pattern70% : migratory polyarthritis with effusion, resolves in the majorityMost affected: ankles, wrists, small joints of handsLower limb & back involvement classical bending phenomenonWHO: Guidelines on clinical management of chikungunya fever, 2008

Lancet 2006; 368: 258J Gen Virol 2007;88:2363-2377

SymptomsOcular manifestationNot commonUveitis, conjunctivitis, optic neuritis, retrobulbar neuritisGenerally recover with good vision

SequelaeArthralgia: 88% complete resolve (12%: chronic arthralgia 3 years)3.7% episodic stiffness & pain2.8% persistent stiffness without pain5.6% persistent painful restriction of joint movements

LabAbnormalitiesLeukopenia, lymphopeniaAnemiaThrombocytopeniaGOT, GPT

DiagnosisReal Time RT-PCRELISA (Capture IgM/IgG)Virus Isolation CDC

Differential diagnosisDengue feverPurpura or active bleeding

LeptospirosisMyalgia localized to calf musclesConjunctival congestion/subconjunctival hemorrhageOliguriaJaundiceHistory of contact to contaminated water

Rheumatic fever

WHO: Guidelines on clinical management of chikungunya fever, 2008

Differential diagnosisKaohsiung J Med Sci 2010;26(5):256-260.CHIKV: Lab

WHO: comprehensive guidelines for prevention & control of dengue & DHF, 2011

TreatmentSymptomatic reliefParacetamol: drug of choice for pain reliefIf not relief NSAIDAvoid aspirinMild forms of exercise + physiotherapyAll suspected case should be kept under mosquito nets during the febrile periodViremia: 2 days before onset ~ 5 days after onset

Case presentation40 y/o woman, travel to Malaysia during 1/22 1/30 in 2009Symptoms: 1/30: fever with chillsCough, sore throat, headache, neck sorenessBilateral arthralgia over knees, wrists & ankles, difficulty in walkingSkin rash over backBilateral conjunctivitis

Lab: Hb: 13 g/dL, WBC: 4070/uL (seg: 85.5%) , PLT: 139KPT: 10.9/10.8; PTT: 31.7/28.3GOT/GPT: 20/12CHIKV PCR (+); the paired serum for CHIKV IgM & IgG (+) Follow up: WBC: 1380/uL, PLT: 111KMild bilateral ankle pain persisted for 30+ daysKaohsiung J Med Sci 2010;26(5):256-260.

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Thanks for your attention !

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