EMERGENCY

050917

MIKROB

Dengue Viral

(SLIDE)

 Dengue fever/ breakbone fever, is an acute communicable disease caused by virus

 Caused by dengue virus (serotypes 1,2,3,4)
 Symptoms;
1. Fever, headache, skin rash, muscle and joint pain
2. Severe form; hemorrhagic fever, fluid leakage, bleeding in the GIT (could be
fatal)
 Prevalent in tropical countries (urban disease)
 Spread by mosquito (Aedes aegypti but in Hongkong by Aedes albopictus) as vector
 Aedes albopictus as a potential vector (in lab)-> mosquito lifes outside home
 Dengue is the biggest arbovirus problem in the world today with over 2 million cases per
year. Dengue is found in SE asia, Africa, and the carribean and south America
 Flavivirus, 4 serotypes, transmitted by aedes mosquitoes which reside in water-filled
containers
 Human infections arise from a human-mosquitoe-human cycle
 Classically, dengue presents with a high fever, lymphadenopathy, myalgia, bone and
joint pains, headache and a maculopapular rash
 Severe cases may present with haemorrhagic fever and shock with a mortality of 5-10%
(dengue hemorrhagic fever or dengue shock syndrome)
 Increased incidence
1. Uncontrolled urbanization
2. Poor water, sewer and waste management
3. Lack of effective mosquito management
4. Global travel (for work and vacation)
5. Lack of public health infrastructure in many countries
6. Demographic and societal changes
 Mode of transmission
1. A healthy person gets the disease when he is bitten by an infected mosquito.
The virus enters his blood from the mosquito’s lava
 2. An infected person could transmit the virus to mosquitoes if he is bitten by a
mosquito anytime from the onset to the subsidence of the fever (a period of
about 6 to 7 days). The disease is then spread by mosquitoes
3. Dengue fever is not spread by contact with infected persons
 Types:
1. Classical dengue
2. Dengue hemorrhagic fever
 Dengue
1. Dengue hemorrhagic fever and shock syndrome appear most often in patients
previously infected by a different serotypes of dengue, thus suggesting an
immunopathological mechanism
2. Diagnosis is made by serology
3. No specific antiviral therapy is available
4. Prevention of dengue in endemic areas depends on mosquito eradication. The
population should remove all containers from their premises which may serve as
vessels for egg deposition
5. A live attenuated vaccine is being tried in Thailand with encouraging results
 The life cycle of a vector mosquito is divided into 4 stages: egg, larva, pupa and adult
 Symptoms of classical dengue
1. Fever: continuous for 3 to 5 days
2. Severe headache
3. Painful limbs, joint pain, muscle pain, back pain, pain behind eyeballs
4. Rash appears on the 3rd to 4th day after onset
5. Nausea, vomiting
6. Slight gum bleeding and nasal bleeding
7. Extreme fatigue and depression may fellow recovery
8. In very rare cases, the condition may worsen into dengue hemorrhagic fever,
leading to hemorrhage, shock or even death
 Dengue virus
1. Member of flaviviridea (same family as west nile virus, Japanese encephalitis
virus, tick-borne encephalitis virus)
2. Uses mosquito (aedes aegypti) as a vector for infecting humans
3. Genus flavivirus
4. 4 strains – DENV 1,2,3,4
5. Rod shape, 45-60nm in diameter
6. Haemagglutinable
7. Thermolabile
8. Sensitive to inactivated by diethyl ether-2, Na-dioxicolate, acid pH, detergent
 9. Stable at 70oC
10. Replication in sitoplasma and passage in RES
 Anatomy of the dengue virus
1. Enveloped virus
2. Has a lipid bilayer coat
3. Genetic material is ssRNA virus (+ive sense)
4. RNA is covered by nucleocapsid
 Dengue virus: RNA and Proteins
1. 11kb positive sense RNA
2. Structural proteins; C, prM, E
3. Non-structural proteins; NS1, NS2A/B, NS3,NS4A/B, NS5
 (PICT)
1. Head: headache, fever
2. face: bleeding gums, nose, eyes
3. vascular symptoms:
 leucopenia
 thrombocytopenia
 neurotropenia
 late eosinophilia
 reduced coagulation
4. vascular symptom correlate to heart
 hypovolemia
 low blood pressure
 shock
5. skin symptoms
 rash
 bruishing
 petechie
 purpura
6. abdomen:
 hepatic injury
 fluid pooling in body cavities
 gall bladder thickening
 hemorrhaging with organs
7. git
 vomiting
 intestinal bleeding
8. joint pain
 9. altered haematopoiesis
10. infrequent complication
 encephalitis
 acute pancreatitis
 renal failure
 myocarditis
 splenic rupture
 pulmonary hemorrhagic
 manfes
1. demam dengue:
 masa inkubasi 1-2 minggu, menggigil, demam sampai 40oC sakit kepala,
sendi dan otot
 demam menurun setelah 7 hari -> macula papula exanthema -> betis
2. demam berdarah dengue
 perdarahan pada kulit dan organ
 ptechie, hidung berdarah (juga pada lubang lain), feses berdarah,
hematturia
3. dengue shock syndrome
 pendarahan pada organ
 masa darah pada otak -> CNS
 10-40% -> meninggal
 Typical infectious cycle
1. Attachment
2. Penetration
3. Uncoating
4. Transcription and/ or translation
5. Replication
6. Assembly release
 Replication strategy of SS (+) RNA viruses, steps in replication:
1. Translation of virion RNA as mRNA (early products = RNA-dependent RNA Pol)
2. Synthesis of (-) sense RNA on (+) sense template by RDRP (=formation of
replication complex, RC)
3. Synthesis of (+) sense RNA, mRNA and (-) sense RNA
4. Translation of (+) sense and mRNA, synthesis of structural protein
5. Assembly of structural protein and (+) sense RNA and maturation of virions
 Pathogenesis dengue
1. Virus menginfeksi monosit -> akibatnya CD4+ dan CD8+ (limfosit T) teraktivasi
->CD8+ (limfosit T) -> serang monosit dan berinteraksi dengan CD4+ -> cytokine
 teraktivasi (IL-1, IL-2, TNF-a) -> permeabilitas kapiler meningkat -> sebabkan
hemorrhagic dan shock syndrome (lebih hebat lagi pada infeksi yang kedua)
 Manfes
1. Syok -> hipersensitivitas, hemokonsentrasi
2. Beberapa hari setelah infeksi kedua dibentuk kompleks virus dan Ab -> ab tidak
menambah netralisasi virus -> komplemen teraktivasi -> memacu infeksi virus ke
sel-sel mononuclear meningkat + pelepasan sitokin, mediator vasoaktif+
prokoagulan -> pembekuan intra vaskuler -> tersebar -> DIC -> syndrome demam
berdarah
 Diagnosis
1. Serology – usually used to make a diagnosis of arbovirus infections
2. Culture – a number of cell lines may be used, including mosquito cell lines.
However it is rarely carried out since many of the pathogens are group 3 or 4
pathogens
3. Direct detection test – e.g detection of antigen and nucleic acids are available
but again there are safety issues
 Isolation and Serology
1. Isolation
 Intracerebral inoculation at baby mouse
 Mammalian cell culture (LLC-MK2)
 Intra thoracal inoculation at mosquito
 Hemaglutinin inhibition test
2. Serology
 CFT
 Netralisasi test
 MC ELISA
 IgG ELISA
 Dengue rapid test
 PCR
 Prevention
1. Surveillance- of disease and vector populations
2. Control of vector- pesticides, elimination of breeding grounds
3. Personal protection – screening of houses, bed nets, insect repellants
4. Vaccination – available for a number of arboviral infections eg. Yellow fever,
Japanese encephalitis, Russian tick-borne encephalitis
 Dengue: prevention & treatment
1. Mosquito control (community based most effective)
2. Vaccine (live attenuated virus (currently acts like an antiviral))
 3. Effective vaccine in development
4. Antivirals (potential target RNA dependent RNA polymerase)

110917

IPD

Keracunan insektisida

(SLIDE)

 Keracunan ini adalah salah satu dari keracunan zat kimia spesifik;
o Organofosfat eg; malathion
o Hidrokarbon chlorinated eg; DDT (dikloridifeniltrikloroetan), aldrin, endrin
o Karbamat
o Insetisida botani
 Penggunaan insektisida meningkat untuk pemberantasan parasit baik di rumah dan di
perkebunan (hama tanaman) -> meningkatkan keracunan juga
 Keracunan bisa
o Akut (suicide)
o Kronis
 Keracunan
o Golongan organofosfat (kolinesterase inhibitor)
o Golongan hidrokarbon klorin
 KERACUNAN OGANOFOSFAT
o Sangat toxik -> insidens cenderung meningkat
o Yang termasuk senyawa ini; parathion, malation, systox, dll
o Insektisida ini mudah dan sangat cepat diabsorpsi (kulit, inhalasi & per oral)
o Menghambat & inaktivasi enzim kolinesterase -> asetilkolin tidak dapat
dihancurkan -> menumpuk pada : SSP, ganglion otonom, ujung-ujung saraf
parasimpatis & motoric
o Gejala klinis timbul 2 jam setelah kontak
o SSP:
 deperesi sel-sel saraf -> kejang-kejang diikuti dengan gangguan kesadaran
& depresi pernapasan
 Penumpukan asetilkolin pada ujung saraf simpatis: miosis, kabur, spasme
otot usus, muntah dan mulut berbuih dan diare
 Stimulasi sekretori gland: rhinorhea, hipersalivasi, hiperhidrosis, kontriksi
otot bronchial, gangguan pernapasan, depresi sinus cardiac pace maker
  Penumpukan asetilkolin yang menetap pada end plate (hubungan neuro-
muskular) -> tremor, kejang, terjadi hambatan impuls neuromuscular
dengan flaccid paralisis
 Manifestasi gangguan pernapasan yang lebih berat-> sianosis dan edema
paru
o Laboratorium: kolinesterase plasma menurun
o Tatalaksana:
 Pendekatan perawatan keracunan
 Stabilkan kesadaran umum pasien (CPR)
 Hilangkan/ keluarkan racun
 Beri antidotum
 Pengobatan/ perawatan keracunan:
 Cegah kontak selanjutnya
 Rangasang muntah& bilas lambung
 Supportif:
o Koreksi & sianosis -> O2
o Koreksi cairan & elektrolit -> IVFD
 Obat-obatan
o ATROPONISASI (flushing, takikardi, midriasis, mulut dan
kulit kering dan panas)
 Pasien sadar: SA 2 mg i.v,kmdn 0,5 mg /30 menit
utk 2 jam pertama(4 mg), selanjutnya 0,25 mg / 8
jam sp tercapai Atropinisasi
 Pasien tidak sadar: SA 4 mg i.v (loading dose) kmdn 2
mg i.v / 30 menit sp o.s sadar, kmd diteruskan 0,5 mg i.v
/ 30 menit sp Atropinisasi (evaluasi tiap 6 jam & k/p
berikan 0,25 mg / 6 jam)*

“Cara Lain” dapat diberikan S.A 2 mg i.v,tiap 5 -
10 menit sp Atropinisasi,dan dosis efektif ini
diteruskan minimal 3 hari - dosis SA ini bisa sp 50
mg dlm 24 jam pertama, bahkan bisa sp 1,5 g dlm 1
hari - SA tdk boleh diberikan bila o.s msh
Cyanosis ventrikel fibrilasi fatal
o PRADILOKSIM
 Senyawa oksim: reaktivator kolinesterase spesifik
untuk meningkat insektisida op yang masih bebas
dalam darah setelah tercapai atroponisasi
  Diberikan 24-48 jam pertama, 1-2gr per infuse
(30mg/ kgBB)
o Anti convulsive
 Kalau diperlukan/ harus hati-hati
 Eg: barbiturate, dll
 Komplikasi
o Aspirasi pneumonia, edema paru, dan resepiration failure
o Heart block-> cardiac failure
 Prognosis
o Akut: terlambat -> jelek
o Kronis: baik
o KERACUNAN H-K CHLORINATED
 Insektisida yang termasuk golongan ini
 Organochlorin
o DDT, TDE (chlorinated di phenil)
o Aldrin, endrin (chl. Polycylic compounds)
 Hexachlorbenzene: lindane
 Senyawa ini: tidak larut dalam air, larut baik dalam lemak, kerosn (pelarut
organic)
 Cara keracunan
 Termakan, inhalasi, kulit (kontak kronis)
 Patogenese
 Pada keracunan akut-> terjadi perangsangan SSP -> kejang ->
vibrilasi ventricle jantung
 Pada keracunan kronis -> liver, kidney, & otak
 Gambaran klinis
 Gejala awal (initial symptoms): nausea, vomitus, cephalgia,
vertigo, hoyong, gelisah, tremor
 Generalized CNS hyperexcitability seperti: delirium, kejang klinik/
tonik dan vibrilasi ventricle (jantung)
 Progressive depression fase: paralisis otot, koma, -> pneumonia &
R.F
 Diagnosis dan diagnosis banding
 Diagnosis
o Riwayat intoksikasi dan klinis
o Pemeriksaan lab (muntahan pasien, darah)
 Diagnosis banding
 o Intoxicate organofosfat
o Intoxicate botulisme
 Tatalaksana
 Bersihkan kulit -> cuci dengan air & sabun
 Keracuna oral -> gastric lavage (( 4 jam I)
 (dgn Air a^ Saline sol. + kan & masukkan kedlm lambung 30 gr
MgSO4)
 Bersihkan jalan napas dan oxygen
 Input cairan -> IVFD (nacl, dextrose)
 Kejang -> anticonvulsant
 Vibrilasi ventricle -> dc shock di ICU
 Pencegahan
 Mengikuti pentunjuk cara pemakaian obat setiap insektisida
dengan benar
 Prognosis
 Keracunan akut->
o segera dirawat -> baik
o terlambat-> jelek
 keracunan kronis – dengan perawatan yang benar akan baik
 komplikasi
 aspirasi pneumonia
o BEBERAPA ANTIDOTUM KERACUNAN (bukan treatment utama)
 Opium alkaloid ... Nalokson
 Parasetamol ..…. Metionin, sisteamin
 Sianida …..…….. Dikobalt edetat
 Organofosfat ….. Pralidoksim + S.A
 Arsen …………... Dimerkaprol
 Mercuri …………. N-Asetil Penisilamin
 Timbal ………….. Ca-Disodium Edetat
 Metanol ………… Etanol
 Antikoagulan (Kumarin) …… Vit.K
