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DENGUE INFECTION
Teddy Septianto
Pendahuluan
• Dengue merupakan penyakit yang disebarkan
oleh nyamuk Aedes aegypti dan Aedes albopictus
• Insidensi global penyakit tersebut meningkat 30
kali lipat dalam 50 tahun terakhir dan terjadi
pada lebih dari 100 negara pada daerah tropis
dan subtropis di dunia
• Faktor penting yang mendukung dinamika
transmisi dengue adalah faktor sosioekonomi,
urbanisasi, dan faktor iklim
Epidemiologi di Indonesia
• Berdasarkan Data
Kemenkes Tahun
2017 :
– Jumlah kasus DBD
 68.407 kasus
– Incidence rate
26,12 per 100000
penduduk
– Kasus meninggal
sebanyak 493
orang
Virologi
• Family: Flaviviridae
• Genus: Flavivirus
• A single-stranded RNA Flavivirus
• 4 types of agents:
– Dengue Virus 1 (DEN-1)
– Dengue Virus 2 (DEN-2)
– Dengue Virus 3 (DEN-3)
– Dengue Virus 4 (DEN-4)
Transmisi Virus
• The Aedes aegypti mosquito is the primary
vector of dengue.
• The virus is transmitted to humans through
the bites of infected female mosquitoes.
• After incubation for 4–10 days, infected
mosquito is capable of transmitting the virus
for the rest of its life.
• Patients who are already infected with the
dengue virus can transmit the infection (for 4–
5 days; max 12) via Aedes mosquitoes after
their first symptoms appear.
Ae. albopictus
Ae. aegypti
Siklus Virus Dengue
Patogenesis dan Patofisiologi
Patogenesis dan Patofisiologi
• In DHF there is no vasculitis and hence no injury to the vessel walls, and plasma
leakage results from cytokine mediated increase in vascular permeability.
Patogenesis dan Patofisiologi
Haemorrhagic Manifestations in DHF
Haemorrhagic Manifestations in DHF
• Thrombocytopaenia is initially due to bone
marrow suppression during the febrile
viraemic phase of the illness.
• Progressive thrombocytopaenia with
defervescence result from immune mediated
platelet destruction.
Haemorrhagic Manifestations in DHF
• The low plasma fibrinogen detected in DHF could thus
be a reflection of loss into the interstitial spaces in the
setting of increased vascular permeability
• Heparan sulphate forms an integral part of the
glycocalyx which when damaged by the initial cytokine
response in DHF gets liberated to the circulation and
acts like an anticoagulant which could explain the
prolonged APTT
• The disturbance in both these important haemostatic
indices are unlikely to cause spontaneous bleeding.
Haemorrhages are triggered by trauma in this setting
of coagulopathy.
Fase Infeksi
DBD
World Health Organization. Dengue Guidelines For
Diagnosis, Treatment, Prevention And Control. France:
World Health Organization; 2009. p.25-102.
Diagnosis
Pemeriksaan Diagnostik
Ag/Ab
level
Day
Ig
M
Ig
G
Immune Response
Sympt
om
NS1
Ag
DA
Y
-7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9
1
0
1
1
1
2
Antibod
y
Bit
e
NS1
Ag
CRITICA
L
PHASE
CONVALESENCE
PHASE
ACUT
E
PHAS
E
█ Response to Primary Infection
1. NS1 antigens
Day 1 after onset of fever and up to Day 9.
Not detectable once anti-NS1 IgG antibodies are
produced.
2. IgM antibodies
Day 5 after onset of fever and rise
for 1-3 weeks, then for up to 60 days.
3. IgG antibodies
Day 14 after onset of fever and persists for life.
Dengue Markers
█ Response to Secondary Infection
1. NS1 antigens
Day 1 after onset of fever and up to Day 9.
Not detectable once anti-NS1 IgG antibodies are
produced
(Appearance in short period )
2. IgM antibodies
Produced at low or undetectable levels or
for a shorter period than in a primary infection.
3. IgG antibodies
Rise rapidly 1-2 days after onset of symptoms.
Dengue Markers
SD Dengue NS1Ag &
IgG/IgM
NS1 Ag
for early acute phase samples
(day 1~5)
IgG/IgM Ab
for early convalescence
phase samples
(after day 3~5)
Ag/Ab
level
Da
y
NS1
Ag
IgM
IgG
Ag/Ab
level
Da
y
NS1
Ag
IgM
IgG
0 1 2 3 4 5 6 7 8 ≥9 0 1 2 3 4 5 6 7 8 ≥9
NS1 Ag + Ab Combo
Ag/Ab
level
Day
NS1 Ag
IgM
IgG
0 1 2 3 4 5 6 7 8 ≥9
Simultaneous detection of Dengue NS1 Ag and IgG/IgM Ab test
together !
It will be perfect to diagnosis of dengue infection from acute to
convalescent stage !
Metode Hasil Spesimen
Waktu Pengambilan Sampel
dari Onset Gejala
Confirmed
dengue
infection
Isolasi virus Positif / Tumbuh Serum dan
Jaringan
1-5 hari
Deteksi Asam Nukleat RT-PCR positif
Deteksi antigen
NS1 Ag positif Serum 1-6 hari
Immunohistokimia
positif
Jaringan
Serokonversi IgM negatif  positif
Serum
Pada fase akut 1-5 hari dan pada
fase konvalesens setelah 15 hari
Serokonversi IgG
negatif  positif atau
peningkatan titer > 4
kali
Highly
suggestive
dengue
infection
IgM IgM positif
Setelah 5 hari
IgG
Kadar IgG yang tinggi (≥
1280)
Pilihan Metode Diagnostik Dengue
Tatalaksana
 Prinsip utama dari penatalaksanaan infeksi dengue adalah
terapi suportif
 Hal yang penting dalam penanganan DBD adalah
pemeliharaan volume cairan dalam sirkulasi.
 Terapi Non-Farmakologis : Tirah baring
 Terapi Farmakologis: Simtomatis : antipiretik (Paracetamol)
bila demam.
Suhendro, Nainggolan L, Chen K, Pohan HT. Demam Berdarah Dengue. Dalam: Setiati S, Alwi I, Sudoyo AW, Simadibrata M,
Setiyohadi B, Syam AF, penyunting. Buku Ajar Ilmu Penyakit Dalam Jilid II. Edisi ke-VI. Jakarta: InternaPublishing; 2015.
h.539-48.
Protokol Penatalaksanaan DBD
• Protokol 1 : Penanganan DBD dewasa tanpa syok.
 Hb, Ht, trombosit normal atau trombosit antara 100.000–
150.000  pasien dipulangkan dengan anjuran kontrol.
 Hb, Ht normal, Trombosit < 100.000  pasien dirawat
 Hb, Ht meningkat dan trombosit normal atau turun 
dirawat
Suhendro, Nainggolan L, Chen K, Pohan HT. Demam Berdarah Dengue. Dalam: Setiati S, Alwi I, Sudoyo AW, Simadibrata M,
Setiyohadi B, Syam AF, penyunting. Buku Ajar Ilmu Penyakit Dalam Jilid II. Edisi ke-VI. Jakarta: InternaPublishing; 2015.
h.539-48.
Protokol Penatalaksanaan DBD
• Protokol 2
• Apabila Ht belum meningkat >20%, pemberian cairan pada
tersangka DBD dewasa di ruang rawat menggunakan
rumus:
• 1500 + {20x(BB-20)} ml
• Dilakukan pemeriksaan Hb, Ht, trombosit setiap 12-24 jam
Suhendro, Nainggolan L, Chen K, Pohan HT. Demam Berdarah Dengue. Dalam: Setiati S, Alwi I, Sudoyo AW, Simadibrata M,
Setiyohadi B, Syam AF, penyunting. Buku Ajar Ilmu Penyakit Dalam Jilid II. Edisi ke-VI. Jakarta: InternaPublishing; 2015.
h.539-48.
• Protokol 3
• Management of
DHF with
Increase of
Haematocrite
>20%
Protokol
Penatalaksanaan
DBD
Protokol Penatalaksanaan DBD
• Protokol 4 - Penatalaksanaan perdarahan spontan pada
DBD dewasa.
• PRC diberikan jika Hb < 10 gr/dl.
• Transfusi trombosit hanya diberikan pada pasien DBD
dengan perdarahan spontan dan masif dengan jumlah
trombosit < 10.000 dengan atau tanpa koagulasi
intravascular diseminata.
Suhendro, Nainggolan L, Chen K, Pohan HT. Demam Berdarah Dengue. Dalam: Setiati S, Alwi I, Sudoyo AW, Simadibrata M,
Setiyohadi B, Syam AF, penyunting. Buku Ajar Ilmu Penyakit Dalam Jilid II. Edisi ke-VI. Jakarta: InternaPublishing; 2015.
h.539-48.
Kaur P, Kaur G. Transfusion support in patients with dengue fever. Int J Appl Basic Med Res. 2014;4(Suppl 1):S8-S12.
doi:10.4103/2229-516X.140708
Protokol
Penatalaksanaan
DBD
• Protokol 5
World Health Organization. Dengue Guidelines For
Diagnosis, Treatment, Prevention And Control. France:
World Health Organization; 2009. p.25-102.
DT DHF.pptx

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DT DHF.pptx

  • 2. Pendahuluan • Dengue merupakan penyakit yang disebarkan oleh nyamuk Aedes aegypti dan Aedes albopictus • Insidensi global penyakit tersebut meningkat 30 kali lipat dalam 50 tahun terakhir dan terjadi pada lebih dari 100 negara pada daerah tropis dan subtropis di dunia • Faktor penting yang mendukung dinamika transmisi dengue adalah faktor sosioekonomi, urbanisasi, dan faktor iklim
  • 3. Epidemiologi di Indonesia • Berdasarkan Data Kemenkes Tahun 2017 : – Jumlah kasus DBD  68.407 kasus – Incidence rate 26,12 per 100000 penduduk – Kasus meninggal sebanyak 493 orang
  • 4. Virologi • Family: Flaviviridae • Genus: Flavivirus • A single-stranded RNA Flavivirus • 4 types of agents: – Dengue Virus 1 (DEN-1) – Dengue Virus 2 (DEN-2) – Dengue Virus 3 (DEN-3) – Dengue Virus 4 (DEN-4)
  • 5. Transmisi Virus • The Aedes aegypti mosquito is the primary vector of dengue. • The virus is transmitted to humans through the bites of infected female mosquitoes. • After incubation for 4–10 days, infected mosquito is capable of transmitting the virus for the rest of its life. • Patients who are already infected with the dengue virus can transmit the infection (for 4– 5 days; max 12) via Aedes mosquitoes after their first symptoms appear. Ae. albopictus Ae. aegypti
  • 8. Patogenesis dan Patofisiologi • In DHF there is no vasculitis and hence no injury to the vessel walls, and plasma leakage results from cytokine mediated increase in vascular permeability.
  • 11. Haemorrhagic Manifestations in DHF • Thrombocytopaenia is initially due to bone marrow suppression during the febrile viraemic phase of the illness. • Progressive thrombocytopaenia with defervescence result from immune mediated platelet destruction.
  • 12. Haemorrhagic Manifestations in DHF • The low plasma fibrinogen detected in DHF could thus be a reflection of loss into the interstitial spaces in the setting of increased vascular permeability • Heparan sulphate forms an integral part of the glycocalyx which when damaged by the initial cytokine response in DHF gets liberated to the circulation and acts like an anticoagulant which could explain the prolonged APTT • The disturbance in both these important haemostatic indices are unlikely to cause spontaneous bleeding. Haemorrhages are triggered by trauma in this setting of coagulopathy.
  • 13. Fase Infeksi DBD World Health Organization. Dengue Guidelines For Diagnosis, Treatment, Prevention And Control. France: World Health Organization; 2009. p.25-102.
  • 15.
  • 17. Ag/Ab level Day Ig M Ig G Immune Response Sympt om NS1 Ag DA Y -7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 Antibod y Bit e NS1 Ag CRITICA L PHASE CONVALESENCE PHASE ACUT E PHAS E
  • 18. █ Response to Primary Infection 1. NS1 antigens Day 1 after onset of fever and up to Day 9. Not detectable once anti-NS1 IgG antibodies are produced. 2. IgM antibodies Day 5 after onset of fever and rise for 1-3 weeks, then for up to 60 days. 3. IgG antibodies Day 14 after onset of fever and persists for life. Dengue Markers
  • 19. █ Response to Secondary Infection 1. NS1 antigens Day 1 after onset of fever and up to Day 9. Not detectable once anti-NS1 IgG antibodies are produced (Appearance in short period ) 2. IgM antibodies Produced at low or undetectable levels or for a shorter period than in a primary infection. 3. IgG antibodies Rise rapidly 1-2 days after onset of symptoms. Dengue Markers
  • 20. SD Dengue NS1Ag & IgG/IgM NS1 Ag for early acute phase samples (day 1~5) IgG/IgM Ab for early convalescence phase samples (after day 3~5) Ag/Ab level Da y NS1 Ag IgM IgG Ag/Ab level Da y NS1 Ag IgM IgG 0 1 2 3 4 5 6 7 8 ≥9 0 1 2 3 4 5 6 7 8 ≥9
  • 21. NS1 Ag + Ab Combo Ag/Ab level Day NS1 Ag IgM IgG 0 1 2 3 4 5 6 7 8 ≥9 Simultaneous detection of Dengue NS1 Ag and IgG/IgM Ab test together ! It will be perfect to diagnosis of dengue infection from acute to convalescent stage !
  • 22. Metode Hasil Spesimen Waktu Pengambilan Sampel dari Onset Gejala Confirmed dengue infection Isolasi virus Positif / Tumbuh Serum dan Jaringan 1-5 hari Deteksi Asam Nukleat RT-PCR positif Deteksi antigen NS1 Ag positif Serum 1-6 hari Immunohistokimia positif Jaringan Serokonversi IgM negatif  positif Serum Pada fase akut 1-5 hari dan pada fase konvalesens setelah 15 hari Serokonversi IgG negatif  positif atau peningkatan titer > 4 kali Highly suggestive dengue infection IgM IgM positif Setelah 5 hari IgG Kadar IgG yang tinggi (≥ 1280) Pilihan Metode Diagnostik Dengue
  • 23. Tatalaksana  Prinsip utama dari penatalaksanaan infeksi dengue adalah terapi suportif  Hal yang penting dalam penanganan DBD adalah pemeliharaan volume cairan dalam sirkulasi.  Terapi Non-Farmakologis : Tirah baring  Terapi Farmakologis: Simtomatis : antipiretik (Paracetamol) bila demam. Suhendro, Nainggolan L, Chen K, Pohan HT. Demam Berdarah Dengue. Dalam: Setiati S, Alwi I, Sudoyo AW, Simadibrata M, Setiyohadi B, Syam AF, penyunting. Buku Ajar Ilmu Penyakit Dalam Jilid II. Edisi ke-VI. Jakarta: InternaPublishing; 2015. h.539-48.
  • 24. Protokol Penatalaksanaan DBD • Protokol 1 : Penanganan DBD dewasa tanpa syok.  Hb, Ht, trombosit normal atau trombosit antara 100.000– 150.000  pasien dipulangkan dengan anjuran kontrol.  Hb, Ht normal, Trombosit < 100.000  pasien dirawat  Hb, Ht meningkat dan trombosit normal atau turun  dirawat Suhendro, Nainggolan L, Chen K, Pohan HT. Demam Berdarah Dengue. Dalam: Setiati S, Alwi I, Sudoyo AW, Simadibrata M, Setiyohadi B, Syam AF, penyunting. Buku Ajar Ilmu Penyakit Dalam Jilid II. Edisi ke-VI. Jakarta: InternaPublishing; 2015. h.539-48.
  • 25. Protokol Penatalaksanaan DBD • Protokol 2 • Apabila Ht belum meningkat >20%, pemberian cairan pada tersangka DBD dewasa di ruang rawat menggunakan rumus: • 1500 + {20x(BB-20)} ml • Dilakukan pemeriksaan Hb, Ht, trombosit setiap 12-24 jam Suhendro, Nainggolan L, Chen K, Pohan HT. Demam Berdarah Dengue. Dalam: Setiati S, Alwi I, Sudoyo AW, Simadibrata M, Setiyohadi B, Syam AF, penyunting. Buku Ajar Ilmu Penyakit Dalam Jilid II. Edisi ke-VI. Jakarta: InternaPublishing; 2015. h.539-48.
  • 26. • Protokol 3 • Management of DHF with Increase of Haematocrite >20% Protokol Penatalaksanaan DBD
  • 27. Protokol Penatalaksanaan DBD • Protokol 4 - Penatalaksanaan perdarahan spontan pada DBD dewasa. • PRC diberikan jika Hb < 10 gr/dl. • Transfusi trombosit hanya diberikan pada pasien DBD dengan perdarahan spontan dan masif dengan jumlah trombosit < 10.000 dengan atau tanpa koagulasi intravascular diseminata. Suhendro, Nainggolan L, Chen K, Pohan HT. Demam Berdarah Dengue. Dalam: Setiati S, Alwi I, Sudoyo AW, Simadibrata M, Setiyohadi B, Syam AF, penyunting. Buku Ajar Ilmu Penyakit Dalam Jilid II. Edisi ke-VI. Jakarta: InternaPublishing; 2015. h.539-48.
  • 28. Kaur P, Kaur G. Transfusion support in patients with dengue fever. Int J Appl Basic Med Res. 2014;4(Suppl 1):S8-S12. doi:10.4103/2229-516X.140708
  • 29. Protokol Penatalaksanaan DBD • Protokol 5 World Health Organization. Dengue Guidelines For Diagnosis, Treatment, Prevention And Control. France: World Health Organization; 2009. p.25-102.