Tatalaksana pada. . Malaria_2950823.pptx

Tatalaksana pada. . Malaria_2950823.pptx

1. Tatalaksana Malaria Tanpa Komplikasi Yovita Hartantri Bekasi, 29 Agustus 2023

2. Pedoman di Indonesia Pedoman WHO

3. Pendahuluan Tujuan program pengendalian malaria di Indonesia adalah mewujudkan Indonesia bebas malaria di tahun 2030 secara bertahap Tujuan pembelajaran : membahas tanda-tanda , pengobatan dan pemantauan pengobatan malaria tanpa komplikasi , meliputi Menjelaskan tanda-tanda malaria tanpa komplikasi Melakukan pengobatan malaria tanpa komplikasi 3. Melakukan p emantauan p engobatan m alaria tanpa k omplikasi

4. I. Tanda- tanda malaria tanpa komplikasi 1. Gejala klinis yang diduga malaria tanpa komplikasi 2. Diagnosis laboratorium malaria tanpa komplikasi

5. 1. Gejala klinis yang diduga malaria tanpa komplikasi Gejala awal malaria tidak spesifik Mirip dengan gejala infeksi virus ( minor systemic viral illness ) Nyeri kepala Nyeri otot dan sendi Nyeri perut Lemah Diikuti dengan demam , menggigil dan berkeringat Mual , muntah

6. Anamnesis Riwayat berkunjung ke daerah endemis malaria. Riwayat tinggal di daerah endemis malaria. Riwayat sakit malaria / riwayat demam . Riwayat minum obat malaria satu bulan terakhir . Riwayat mendapat transfusi darah . Riwayat menginap / tinggal di hutan .

7. Demam Anemia Splenomegali Tanda- tanda malaria

8. Tipe Demam Malaria Plasmodium Proses Skizogoni Pl. falsiparum 36 -48 jam Pl. vivax / ovale 48 jam Pl. malariae 72 jam Pl. knowlesi 24 jam

9. Siklus hidup Schizogony : human Sporogony : female Anophelin mosquito

10. Siklus hidup plasmodium

11. Patogenesis Demam Timbul bersamaan dengan pecahnya skizon darah yang mengeluarkan macam-macam antigen. Antigen merangsang sel-sel makrofag , monosit atau limfosit untuk mengeluarkan sitokin (TNF). TNF dibawa aliran darah ke hipotalamus , dan terjadi demam .

12. Patogenesis Splenomegali Limpa merupakan organ retikuloendotelial . Plasmodium dihancurkan oleh makrofag dan limfosit . Penambahan sel radang ini menyebabkan limpa membesar

13. Patogenesis Anemia Karena pecahnya eritrosit yang terinfeksi , p. falsiparum menginfeksi seluruh stadium eritrosit sehingga anemi terjadi pada infeksi akut dan kronik

14. Masa inkubasi Plasmodium Masa inkubasi (rata-rata) Pl. falsiparum 8 – 25 hari (12 ) Pl. vivax 8 – 27 hari (15) Pl. ovale 15 – 18 hari (17) Pl. malariae 15 – 40 hari (28) Pl. knowlesi 9 – 12 hari (11)

15. Gejala pada anak Dapat disertai : Letargi Napsu makan yang buruk Batuk Bila tidak segera diobati , atau obat yang diberikan tidak efektif , maka akan menjadi malaria berat

16. Gejala pada anak Gejala tidak spesifik : Demam Batuk - pilek Diare Anemia Lakukan apus darah malaria pada semua kasus anak dengan demam Puspo R, Timika Papua

17. 2. Diagnosis laboratorium malaria tanpa komplikasi Wilcocks C, Manson's tropical diseases, 2014

18. Diagnosis Malaria Semua kasus dugaan Malaria harus dikonfirmasi dengan pemeriksaan parasitologi ( Mikroskopik atau RDT) → Hasil pemeriksaan harus tersedia dalam waktu < 2jam

19. Pemeriksaan Mikroskopis Sediaan darah tebal & tipis merupakan Gold standard : - membedakan spesies dan stadium Plasmodium - menghitung jumlah parasit malaria - sesuai dengan level “malaria klinis / simtomatik ” yaitu 50-100 parasite/µL

20. Rapid diagnostic test (RDT) malaria

21. Perbedaan pemeriksaan

22. 2. Pengobatan malaria tanpa komplikasi Jenis obat malaria Perawatan suportif untuk malaria tanpa komplikasi : Konseling kepatuhan minum obat Pemantauan pengobatan

23. 1. Jenis obat Malaria tanpa komplikasi WHO - 2021

24. Strong recommendation for ACT (WHO-2022) Treat children and adults with uncomplicated P. falciparum malaria (except pregnant women in their first trimester) : artemether + lumefantrine artesunate + amodiaquine artesunate + mefloquine dihydroartemisinin + piperaquine artesunate + sulfadoxine –pyrimethamine (SP) artesunate + pyronaridine (currently unGRADEd , anticipated to be updated in 2022) WHO Guidelines for Malaria – 2022 Nsanzabana C, Resistance to ACTs : Do Not Forget The Partner Drug, Tropical Medicine & Infectious Disease, 2019 ACT failure is not only due to artemisinin resistance, but also to the failure of partner drugs

25. Obat anti malaria di Indonesia ACT + Primakuin

26. Lini pertama Dihydroartemisin + Piperakuin (Fixed Dose Combination/FDC) Dihydroartemisin 40mg/tab, dosis 2-4 mg/ kgBB Piperakuin 320mg/tab, dosis 16-23 mg/ kgBB Dosis : 1x4 tablet selama 3 hari Nama dagang : Arterakin , Darplex , D- atepp Efek samping : hepatotoksik

27. Lini kedua ( obat alternatif ) Quinin + Doksisiklin / Tetrasiklin / Clindamisin Cure rate cukup tinggi sp 100% bila dengan dosis komplet Quinin : 10 mg/ kgBB / hari , 3x Doksisiklin : 3,5 mg/ kgBB / hari Tetracycline: 4 mg/ kgBB , 4x Clindamycin : 10 mg/ kgBB , 2x

28. Dihidroartemisinin-piperakuin

29. Factors associated with altered drug exposure High-fat meals should be avoided , significantly accelerate the absorption of piperaquine , thereby increasing the risk for potentially arrhythmogenic delayed ventricular repolarization Piperaquine prolongs the QT interval by approximately the same amount as chloroquine but by less than quinine. It is not necessary to perform an electrocardiogram before prescribing DHP But ACT should not be used in patients with congenital QT prolongation or who have a clinical condition or are on medications that prolong the QT interval. Although there is a theoretical concern about bradycardia and QTc prolongation associated with artemisinin derivatives, particularly at high doses , this has not been seen with artesunate

30. Pencegahan relaps Malaria vivax / ovale

31. Rekomendasi Dosis Primakuin untuk Malaria falciparum diturunkan dari 0.75 mg/ kgBB menjadi 0.25 mg/kg BB di seluruh daerah lndonesia Primakuin dapat diberikan pada anak > 6 bulan Komli Malaria – Terapi (2016)

32. 3. Pemantauan pengobatan Metode untuk penilaian resistensi parasit terhadap obat malaria R esistensi parasit terhadap obat malaria

33. Metode penilaian pengobatan Sembuh : gejala klinis ( demam ) hilang dan parasit aseksual tidak ditemukan pada hari ke-4 pengobatan sampai dengan hari ke-28 Early treatment failure Menjadi malaria berat pada hari ke-1 sampai hari ke-3 dengan parasitemia Hitung parasit pada hari ke-2 > hari ke-0 Hitung parasit pada hari ke-3 > 25% hari ke-0 Ditemukan parasit aseksual pada hari ke-3 disertai demam

34. Metode penilaian pengobatan Late treatment failure a. Gagal Pengobatan Klinis dan Parasitologis 1) Menjadi malaria berat pada hari ke-4 sampai ke-28 dan parasitemia 2) Ditemukan kembali parasit aseksual antara hari ke-4 sampai hari ke-28 disertai demam b. Gagal Parasitologis Ditemukan kembali parasit aseksual dalam hari ke-7, 14, 21 dan 28 tanpa demam .

35. Recurrence is the recurrence of asexual parasitemia following treatment in pl. vivax and pl. ovale infections only or a new infection

36. Recurrent falciparum malaria Recurrence of P. falciparum malaria can result from re-infection or recrudescence (treatment failure) Treatment failure may result from drug resistance or inadequate exposure to the drug due to sub-optimal dosing, poor adherence, vomiting, unusual pharmacokinetics in an individual, or substandard medicines. It is important to determine from the patient’s history whether he or she vomited the previous treatment or did not complete a full course of treatment.

37. Relapse is the recurrence of asexual parasitemia in Pl. vivax or Pl. ovale malaria deriving from persisting liver stages from hypnozoites Malaria case attributed to activation of hypnozoites of P. vivax or P. ovale acquired previously After an interval of weeks or months , the hepatic schizonts burst and liberate merozoites into the bloodstream

38. Recrudescence is the recurrence of asexual parasitemia after the treatment of the infection with the same infection due to incomplete clearance of asexual parasitaemia of the same genotype(s) that caused the original illness. a recrudescent case must be distinguished from reinfection and relapse, in the case of P. vivax and P. ovale

39. Reinfection a new infection that follows a primary infection can be distinguished from recrudescence by the parasite genotype , which is often (but not always) different from that which caused the initial infection

40. Resistance The ability of a parasite to survive or multiply despite properly administered and dosed medication An important marker of resistance is delayed parasite clearance times. A major challenge with assessing antimalarial efficacy in the era of combination therapy is that failure may not be observed even when the parasites are resistant to one of the partner drugs . Cowell AN, Winzeler . EA. The genomic architecture of Antimalarial drug resistance, 2019

41. The timeline between the introduction of the main antimalarial drugs and the first case of emergence of resistance Duru V et al. Am J Trop Med Hyg, 2016

42. Mechanism of resistance Shibeshi MA et al, Antimalarial Drug Resistance and Novel Targets for Antimalarial Drug Discovery, Infection and Drug Resistance 2020

43. Key finding : 10 years of surveillance Data from 66,000 patients worldwide ACTs remain effective in curing pl. falciparum High treatment failure rate were reported, policy changes have been made or are ongoing In 4 countries in Greater Mekong subregion ( Cambodia, Laos, Thailand, Vietnam ) high treatment failure rates were detected, at least 2 other ACT options that could effectively treat pl. falciparum malaria Overall average efficacy rates for these 3 medicines were consistently high : AL (98%) AS– AQ (98.4%) DHA – PPQ (99.4%)

44. Monitoring efficacy and safety of antimalarial drug and resistance Routine surveillance WHO promotes universal coverage with diagnostic testing and antimalarial treatment and strengthened malaria surveillance system The “test”, “track”, “treat” initiative Therapeutic efficacy Assessing clinical and parasitological outcome of treatment for at least 28 days after the start of adequate treatment PCR genotyping should be used to distinguish between recrudescence and new infections Antimalarial medicine should be changed if the total treatment failure proportion is ≥ 10%, as assessed in vivo by monitoring therapeutic efficacy WHO Guideline for Malaria - 2022

45. Clinical and parasitological assessment of therapeutic efficacy should include: confirmation of the quality of the antimalarial medicines tested molecular genotyping to distinguish between re-infections and recrudescence and to identify genetic markers of drug resistance; studies of parasite susceptibility to antimalarial drugs in culture ; and measurement of antimalarial drug levels to assess exposure in cases of slow therapeutic response or treatment failure WHO Guidelines for Malaria - 2022 (Recurrent Falciparum Malaria)

46. Failure within 28 days Failure after 28 days The recommended second-line treatment is an alternative ACT known to be effective in the region 7-day treatment regimens (with artesunate or quinine with + tetracycline, or doxycycline or clindamycin) is likely to be poor if treatment is not directly observed; These regimens are no longer generally recommended. May be due to either recrudescence or a new infection. The distinction can be made only by PCR genotyping of parasites from the initial and the recurrent infections. PCR is not routinely used, all presumed treatment failures after 4 weeks of initial treatment should be considered new infections and be treated with the first-line ACT. WHO Guidelines for Malaria - 2022 (Recurrent Falciparum Malaria)

47. Core Principles of Malaria Case Management Early diagnosis and prompt effective treatment of malaria → within 24-48 h of the onset of symptom Rational use of antimalaria agents Combination therapy Appropriate weight-based dosing WHO Guideline Malaria - 2015

48. Terimakasih