infeksi dengue di populasi dewasa dan terapi

Gambaran umum penyakit dengue

1. Dengue Haemorragic Fever Heri Sutanto

2. PAHO 2022 WHO 2011 SOUTH-EAST ASIA PAN AMERICAN

3. INTRODUCTION The most important and most frequent arbovirus ( AR thropod- BO rne VIRUS ) DENGUE C aused by DENgue Virus ( DENV 1-4 ) belonging to family Flaviviradae Aedes aegypti mosquito is the main transmission vector F ound in tropical and subtropical regions around the world, predominantly in urban and semi-urban areas 2.5 billion people around the world at risk 50 million case occur annually 1.3 billion WHO (2011) PAHO (2022)

4. AFIRE study Mengkonfirmasi Dengue merupakan Penyebab tersering Sindroma Demam Akut Indonesia The proportion of acute dengue infections within acute fever cases PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0007785

5. Sekitar 75% kasus dengue terjadi pada golongan usia 5-44 tahun dengan proporsi kematian terbesar se kitar 40% terjadi pada golongan usia 5-14 tahun <1 tahun 1-4 tahun 5-14 tahun 15-44 tahun >44 tahun 2,43% 12,20% 36,10% 38,01% 11,25% Proporsi penderita per golongan umur tahun 2021 Rerisiko terinfeksi Dengue Ref :1. Surya A. 2022 Penanggulangan Dengue di Indonesia. Dipresentasikan pada Diskusi Media Pencegahan Dengue, Jakarta : 19 April 2022.

6. Pakasi, T . T . 2022. Penanggulangan Dengue di Indonesia. Dipresentasikan pada Diskusi Media Pencegahan Dengue. Dipresentasikan pada Diskusi Media Hari Anak Nasional: Perlindungan Keluarga dari Bahaya Demam Berdarah Dengue: 20 Juli 2022 The highest proportion of dengue incidence cases were found among productive age Dengue Incidence in Indonesia by Age Group Cases Proportion by age group Death Proportion by age group

7. Meskipun berbagai upaya promosi pengendalian dengue telah dilakukan, d engue masih tetap menjadi tantangan masalah kesehatan publik Biaya kasus dengue rawat inap derajat ringan-sedang sekitar 4,5 juta rupiah (US$ 316.24) Biaya kasus dengue rawat jalan sekitar 3,2 juta rupiah (US$ 22.45) Beban Ekonomi yang tinggi 8 Lebih dari 50 t ahun d engue di Indonesia Setiap hari ~ 2 orang ~116,000 Rata-rata Kasus dengue per tahun selama 5 tahun terakhir 2016-2020 1 -5 meninggal karena dengue 1 -5 Infeksi dengue merupakan penyakit yang ditularkan melalui vektor dengan penyebaran tercepat di dunia 6 Indonesia secara konsisten menjadi salah satu dari tiga negara teratas dengan beban dengue tertinggi secara global 7 Insiden dengue di Indonesia pada tahun 2016 – 2020 1- 5 1. Kementerian Kesehatan RI. 2017. Profil Kesehatan Indonesia ahun 2016. 2 Kementerian Kesehatan RI. 2018. Profil Kesehatan Indonesia Tahun 2017.3.Kementerian Kesehatan RI. 2019. Profil Kesehatan Indonesia Tahun 2018. 4.Kementerian Kesehatan RI. 2020. Profil Kesehatan Indonesia Tahun 2019.5.Kementerian Kesehatan RI. 2021. Profil Kesehatan Indonesia Tahun 2020. 6.WHO. 0e1'41l18 and severn der,; iue 111fog􀀌 13 Nov2019. httpsi / Www.who.irt / nuffl-mecla /det􀀛 ts /dengue-and-severe- dongue . Accessed 16 Marth 2022. 7. INFODATIN. Situasi Penyakit Demam Berdarah di Indonesia 2017. Kemenkes RI. https:// pusdatin.kemkes.go.id. Accessed 24 Agustus 2022. 8. Nadjib M, Setiawan E, Putri S, Nealon J, Beucher S, Hadinegoro SR, et al. (2019) Economic burden of dengue in Indonesia. PLoS Negl Trop Dis 13(1): e0007038. https://doi.org/10.1371/journal. pntd.0007038.

8. Sejak tahun 1970-an hingga 1990-an, DENV-3 bertanggung jawab atas hampir semua wabah demam berdarah 1 Awal 2000-an: DENV-1 dan DENV-2 mendominasi kasus dengue di Indonesia 1 2008–2012: DENV-1 mendominasi di sebagian besar wilayah Indonesia 1 Sejak 2014: DENV-2 mendominasi secara nasional, tetapi tidak di setiap wilayah 1 Sirkulasi k eempat s erotipe dan p ergeseran d ominasi Distribusi serotipe dengue berdasarkan provinsi di Indonesia selama 1996–2013 2* * Diukur melalui penilaian PRNT 50 profil antibodi monotypic anti-dengue DENV: virus dengue; DBD: demam berdarah dengue; PRNT: uji netralisasi reduksi plak Harapan, dkk . Rev Med Virol 2019; e2037 Sasmono , dkk . PLoS Negl Trop Dis 2018;12:e0006616

9. I nfeksi sekunder dengan serotipe DENV lain ( heterotypic reinfection ) dapat meningkatkan risiko kasus dengue berat Ref. 1. Anderson KB, Gibbons RV, Cummings DA, et al. J Infect Dis. 2014;209(3):360-368. 2. Heinz FX, Stiasny K. Microbiol Mol Biol Rev. 2017;81: e00055-16; . Hal ini dapat disebabkan oleh mekanisme Antibody-Dependent Enhancement , dimana antibodi cross-reactive yang terbentuk pada infeksi primer berada dibawah protective level sehingga memiliki kemampuan netralisasi yang rendah 1

10. Incidence rate (per 100,000 person-years) and case fatality rate (%) of dengue hemorrhagic fever in Indonesia from 1968 to 2017 Harapan et al. BMC Res Notes (2019) 12:350

11. Distribution of dengue immune status and acute infections in 7 cities in Indonesia Dengue infections: 32% Primary/Secondary infections 15%:85% PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0007785

12. AFIRE study: clinical severity Dengue Fever (DF): 187 (40%) DHF grade I and II : 270 (57.7%) DHF grade III , IV and atypical manifestation: 11 (2.3%) Primary infection: 71 cases S econdary infection: 397 cases The severe cases were more common in secondary than primary infection Mortality due to DENV infection was low (3/468: 0.6%). PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0007785

13. Serotype, type of infections and severity Type of infections D F DHF 1 and 2 DHF 3, and 4, encephalitis D1 D2 D3 D4 D1 D2 D3 D4 D1 D2 D3 D4 Prim ary 10 5 15 11 8 9 1 Se condary 24 17 66 10 54 52 87 10 3 8 Severe cases (dhf gr 3,4, encephalitis) are more common in secondary infection 2.8%(11/390) compared to primary infections 0%(0/68), p value 0.16 All the 11 severe cases are associated with DENV-1 or DENV-3 (4%), and none of them with DENV-2 dan DENV-4 (p=0.04). PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0007785

14. Aedes mosquitoes (dengue virus vectors) BioMed Research International Volume 2021, Article ID 4224816 https://doi.org/10.1155/2021/4224816

15. Pathogenesis dengue according to phase of illness

16. Original antigenic sin and antibody-dependent enhancement in DENV infection. Frontiers in Immunology July 2022 | Volume 13 | Article 889196

17. PAHO (2022)

18. Natural course of dengue infection SEARO, 2011 Kularatne and Dalugama , Clinical Medicine 2022 Vol 22, No 1: 9–13

19. Natural course of dengue infection CDC Yellow Book 2024

20. Warning signs strongly associated with severe disease I ncreased haematocrit with a concurrent decrease in platelet count ( OR = 5.13 ; 95% CI : 1.61–16.34) A bdominal pain ( OR = 2.00 ; 95% CI : 1.49–2.68) L ethargy ( OR = 2.73 ; 95% CI : 1.05–7.10) V omiting ( OR = 1.80 ; 95% CI : 1.43–2.26) H epatomegaly ( OR = 5.92 ; 95% CI : 3.29–10.66) A scites ( OR = 6.30 ; 95% CI : 3.75–10.60) P leural effusion ( OR = 5.72 ; 95% CI : 3.24–10.10) M elena ( OR = 4.05 ; 95% CI : 1.64–10.00). Tsheten et al. Infect Dis Poverty (2021) 10:123 https://doi.org/10.1186/s40249-021-00908-2

21. Course of Dengue Illness Anoopkumar , Aneesh, Environment, Development and Sustainability (2021) 23:11217–11239 Yip WCL. Dengue Hemorrhagic Fever: Current Approaches to Management. Medical Progress. October 1980

22. Dengue and its link with other disease complications after dengue virus infection and disease severity Bhattacharjee et al. Pathogens 2023,12,635. https:// doi.org / 10.3390/pathogens12050635

23. Dengue in special situation Patients with co-morbidity : Diabetes, Hypertension, Ischaemic H eart Disease, Coagulopathies, Morbid Obesity, Renal Failure, Chronic Liver disease, COPD Elderly (more than 65 years old) Pregnancy

24. Clinical predictor of severe dengue C hild ( OR = 1.96; 95% CI : 1.22–3.13 ) S econdary infection ( OR = 3.23; 95% CI : 2.28–4.57) P re-existing diabetes ( OR = 2.88; 95% CI : 1.72–4.81) R enal disease ( OR = 4.54; 95% CI : 1.55–13.31). Tsheten et al. Infect Dis Poverty (2021) 10:123 https://doi.org/10.1186/s40249-021-00908-2

25. Severe Dengue GROUP C : Require Emergency Treatment Presumtive Diagnosis Live/travel to dengue endemic area . Fever or two of the following criteria : Anorexia and nausea Rash Aches and pains Warning signs Leukopenia Tourniquet test positive Laboratory confirmed dengue (Important when no sign of plasma leakage) Dengue Case Management Warning Sign Abdominal pain or tenderness Persistent Vomitting Clinical fluid Accumulation Mucosal Bleed Lethargy, restlessness Liver enlargement > 2cm Laboratory : Increase in HCT concurent with rapid decrease in platelet count \ * (requiring strict observation and medical interve n tion) Negative Co-existing conditions Social Circumstances Positive Without Warning Sign GROUP A : Maybe sent Home With Warning Sign GROUP B : Reffered for in-hospital care Negative Positive WHO,2009

26. In patients diagnosed with arboviral infection, should an intense oral hydration scheme be used? —QUESTION 1 —

27. PAHO (2022) ORAL HYDRATION Intense hydration with oral rehydration salts : Healthy adults: up to 3,000 ml per day Pediatrics : Holliday-Segar formula plus 5% WHO 2011

28. In dengue patients with warning signs, should parenteral hydration be indicated? Should resuscitation with crystalloids or colloids be initiated? —QUESTION 2 —

29. WHO (2011)

30. In dengue patients with thrombocytopenia, should the transfusion of blood components (platelet concentrate or fresh frozen plasma) be indicated? —QUESTION 3 —

31. PAHO (2022) WHO (2011) BLOOD TRANSFUSION 10 ml/kg of fresh whole blood or 5 ml/kg of freshly packed red cells Platelet transfusion is not recommended for thrombocytopenia (no prophylaxis platelet transfusion)  may be considered in adults with underlying hypertension and very severe thrombocytopenia (less than 10 000 cell/mm 3 ).

32. In patients with arboviral infection, what pharmacological interventions may be indicated to manage symptoms (pain and fever) ? —QUESTION 4 —

33. (PAHO 2022) PHARMACOLOGICAL INTERVENTIONS NSAIDs  probably the most effective symptomatic control, but could be associated gastrointestinal discomfort ( nausea/abdominal pain) and hemorrhages Paracetamol  may not increase risk of bleeding / acute liver failure when given at normal doses, although it may be associated with a reversible increase in transaminases. Metamizole  may not be associated with hemorrhages / other major complications (marrow aplasia) S teroids and antihistamines  the panel considered their potential efficacy as negligible or uncertain.

34. In patients with severe arboviral infection, should treatment with systemic steroids be indicated? —QUESTION 5 —

35. SYSTEMIC STEROID PAHO (2022)

36. In patients with severe arboviral infection, should treatment with immunoglobulins be indicated? —QUESTION 6 —

37. IMMUNOGLOBULIN PAHO (2022)

38. DISCHARGE WHO (2011)

39. D engue Prevention 1. Harapan , et al. 2019. BMC research notes 12.1: 1-6. 2. https://www.who.int/news-room/questions-and-answers/item/dengue-vaccines 3. WHO. Global Strategy for Dengue Prevention and Control. 2012-2020.https:// www.who.int /immunization/sage/meetings/2013/ april /5_Dengue_SAGE_Apr2013_Global_Strategy.pdf 4. Kemenkes RI. Strategi Nasional Penanggulangan Dengue 2021-2025. 3M PLUS Vector Control with 3M Plus • Draining and brushing • Closing the water reservoirs • Recycle used goods Dengue Vaccination • Increase immunity • Reducing the risk of severe dengue and inpatient Vaccines Wolbachia Inovation The bacteria were inoculated into the eggs of the Aedes aegypti

40. 12 Diskes Kabupaten Badung. 2022. https://diskes.badungkab.go.id/pengumuman/46626- rekomendasi-papdi- tentang-pemberian- vaksinasi- dengue-pada- orang- dewasa Diakses 31 Januari 2023 Dengue Vaccination Recommendation in Adult

41. Terima Kasih