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"[ABSTRAKTingkat bebas parasit dini merupakan gambaran fungsi dari aktivitas artemisinin. Beberapa faktor yang dianggap berperan terhadap bebas parasit hari pertama setelah pengobatan salah satunya adalah kepadatan parasit sebelum pengobatan. Penelitian ini bertujuan untuk mengetahui hubungan antara kepadatan parasit sebelum pengobatan dengan bebas parasit pada hari pertama setelah pengobatan dihidroartemisinin-piperakuin pada anak dengan malaria tanpa komplikasi di enam propinsi di Indonesia. Desain penelitian ini adalah kohort retrospektif yang dianalisis dengan cox regression dan menggunakan data sekunder efikasi dan keamanan obat dihidroartemisinin-piperakuin (DP) di enam propinsi di Indonesia. Kejadian tidak bebas parasit pada penelitian ini sebesar 31,74%. Terdapat hubungan yang bermakna secara statistik antara kepadatan parasit sebelum pengobatan dengan kejadian bebas parasit setelah hari pertama setelah pengobatan, dimana kepadatan parasit >20000/μl mempunyai risiko tidak bebas parasit sebesar 2,327 kali (CI 95% 1,418-3,820, p-value = 0,001) dibandingkan kepadatan parasit <4000/μl dan kepadatan parasit 4000-20000/μl berisiko tidak bebas parasit sebesar 1,669 kali (CI 95% 1,099-2,533, p-value = 0,016) dibandingkan kepadatan parasit <4000/μl setelah dikendalikan faktor jenis parasit dan wilayah. Kepadatan parasit (μl) dapat dijadikan pemeriksaan standar penderita malaria dan penilaian pengobatan.

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ABSTRACTEarly parasite clearance is the function of artemisinin?s activity. One of the factors that are related to parasite clearance on the first day after treatment is parasite density pre treatment. The aim of this study was to determine the relationship between parasite density pre treatment and parasite clearance on first day after treatment in children with uncomplicated malaria at six provinces in Indonesia. The design of this study was retrospective cohort and analyzed with cox regression and used the secondary data of efficacy and safety of dihydroartemisinin-piperaquine (DP) at six provinces in Indonesia. The proportion of uncleared parasite in this study was 31,74%. There was statically relationship between parasite density pre treatment and parasite clearance on the first day after treatment, where parasite density >20000/μl had uncleared parasite? risk 2,327 times (CI 95% 1,418-3,820, p-value = 0,001) more than parasite density <4000/μl and parasite density 4000-20000/μl had uncleared parasite? risk 1,669 times (CI 95% 1,099-2,533, p-value = 0,016) more than parasite density <4000/μl after controlled by Plasmodium species and region. Parasite density (μl) can be used as standard tests for patients with malaria and treatment evalution., Early parasite clearance is the function of artemisinin’s activity. One of the factors that are related to parasite clearance on the first day after treatment is parasite density pre treatment. The aim of this study was to determine the relationship between parasite density pre treatment and parasite clearance on first day after treatment in children with uncomplicated malaria at six provinces in Indonesia. The design of this study was retrospective cohort and analyzed with cox regression and used the secondary data of efficacy and safety of dihydroartemisinin-piperaquine (DP) at six provinces in Indonesia. The proportion of uncleared parasite in this study was 31,74%. There was statically relationship between parasite density pre treatment and parasite clearance on the first day after treatment, where parasite density >20000/μl had uncleared parasite’ risk 2,327 times (CI 95% 1,418-3,820, p-value = 0,001) more than parasite density <4000/μl and parasite density 4000-20000/μl had uncleared parasite’ risk 1,669 times (CI 95% 1,099-2,533, p-value = 0,016) more than parasite density <4000/μl after controlled by Plasmodium species and region. Parasite density (μl) can be used as standard tests for patients with malaria and treatment evalution.]"

"Artemisinin merupakan senyawa SOH-seskuiterpen lakton dengan gugus unik peroksida yang berhasil diisolasi dari tanaman Artemisia annua. Dari hasil uji in vitro dan in vivo, artemisinin terbukti efektif melawan malaria dan menunjukkan hasil yang menggembirakan, bahkan untuk galur Plasmodium yang telah kebal sekalipun. Dihidroartemisinin adalah salah satu derivat artemisinin dari hasil semisintesis sederhana, yang lebih poten dari artemisinin. Penelitian ini bertujuan memodifikasi struktur artemisinin menjadi dihidroartemisinin menggunakan katalis Ni/TiO2 melalui proses hidrogenasi dan mengkaji aktivitasnya sebagai antimalaria melalui uji in vitro. Cara baru modifikasi struktur artemisinin menjadi derivatnya dihidroartemisinin telah berhasil dilakukan melalui reaksi hidrogenasi menggunakan katalis Ni/TiO2 Sintesis senyawa ini menghasilkan kristal berbentuk jarum dengan titik leleh 151- 153oC. Rendemen yang diperoleh sebesar 16.58%. Analisa TLC dengan plat silika gel 60 F254 menggunakan eluen toluene: etil asetat: asam formiat menunjukkan satu spot dengan Rf 0,44. Analisa LC-MS menunjukkan satu puncak dengan tR 2.2 menit serta berat molekul 284.29 sama dengan dihidroartemisinin yaitu C15H24O5. Spektrum IR menunjukkan adanya gugus hidroksil pada frekuensi 3371.57 cm-1 didukung dengan munculnya pita serapan dari vibrasi ulur C-O pada frekuensi 1034.14 cm-1. Reaksi hidrogenasi tidak merusak keberadaan gugus endoperoksida. Hal ini terbukti dengan masih terdapatnya serapan vibrasi ulur dari C-O-O-C pada frekuensi 1091.71; 875.68; 844.82 cm-1. Dari data NMR membuktikan bahwa senyawa tersebut adalah campuran rasemat STX/ETX dihidroartemisinin. Senyawa ini mempunyai aktivitas antimalaria dengan IC50 0.20 nM, melalui uji in vitro menggunakan biakan Plasmodium falciparum kultur 3D7.

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Artemisinin is a SOH-sesquiterpene lactone that incorporates an endoperoxide moiety. This compound is isolated as the active compound of Artemisia annua. Based on the result of in vitro and in vivo assay, artemisinin is an effective antimalarial drug and it shows possitive result, moreover strain of Plasmodium resistant. Dihydroartemisinin is the simplest semisynthetic derivative of artemisinin and is more potent than artemisinin. The objective of this research are to modify the structure of artemisinin into dihydroartemisinin. A new way to modify the structure of artemisinin into dihydroartemisinin, had been successfully done using hydrogenation process with Ni/TiO2 catalyst, and the result was a soft white needle like crystal with melting point of 151-153oC. The yield of the crystal was 16.58%. the TLC analysis on TLC plate silica gel 60 F254 using toluene: etil asetat: asam formiat showed a spot with Rf 0.44. LC-MS analysis showed that the compound contained mainly a peak with tR 2.2 minutes and mass spectrum showed that the molecular weight of the compound was 284.29 which is similar to that of dihydroartemisinin, C15H24O5. The IR spectrum showed that there was a spectrum from C-O in a frequency of 1034.14 cm-1. Hydrogenation reaction did not destroy the existance of endoperoxide group. This was proven by the existance of C-O-O-C in a frequency of 1091.71; 875.68; 844.82 cm-1. NMR data showed that the compound was the mixture of racemic. The compund also had the activity of antimalarial with IC50 0.20 ng/ml by using in vitro test with Plasmodium falciparum strain 3D7."

"ABSTRAKSebanyak 120 sampel Dried Blood Spot (DBS) malaria falciparum yang diperoleh dari studi efikasi obat DHP pada 5 wilayah di Indonesia dianalisis dengan Polymerase Chain Reaction (PCR) dan sekuensing, untuk melihat varian SNPs K13 dan alel FcγRIIa -131 serta hubungannya dengan densitas parasit dan efikasi Dihidroartemisinin-Piperakuin. Hasil penelitian tidak menemukan mutasi gen K13 pada seluruh isolat P. falciparum yang diperiksa. Artemisinin masih efektif untuk pengobatan malaria di Indonesia. Analisis gen FcγRIIa menunjukkan bahwa genotip RH memiliki frekuensi yang paling tinggi (50,8%) dibandingkan RR (17,5%) dan HH (31,7%). Alel R131 gen FcγRIIa menunjukkan efek protektif terhadap High Density Parasitemia (HDP) (>5000 parasit/μL; odds ratio [OR]= 0.133, 95% confidence interval [CI]= 0.053?0.334, P< 0.001) dan berkaitan dengan keberadaan gametosit yang lebih lama pada inang (> 72 jam.

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ABSTRACT

Relative Risk [RR]= 1,571, 95% confidence interval [CI]= 1,005?2,456, P= 0.090).;A total of 120 samples of Dried Blood Spot (DBS) falciparum malaria acquired from DHP drug efficacy studies in 5 regions in Indonesia were analyzed by Polymerase Chain Reaction (PCR) and sequencing, to look at variants of K13 SNPs and FcγRIIa-131 allele and its Association with Parasite Density and Efficacy of Dihydroartemisinin- Piperaquine. No mutations in the K13 gene was found in any of the isolates examined. Artemisinin is still effective for the treatment of malaria in Indonesia. The FcγRIIa gene analysis indicated that genotype RH has the highest frequency (50.8%) compared to RR (17.5%) and HH (31.7%). Allele R131 showed a protective effect against High Density Parasitemia (HDP) (>5000 parasites/μL; odds ratio [OR]= 0.133, 95% confidence interval [CI]= 0.053?0.334, P< 0.001) and associated with longer gametocytes carrier clearance time (> 72 hours; Relative Risk [RR]= 1,571, 95% confidence interval [CI]= 1,005?2,456, P= 0.090)."