Uji efikasi kombinasi Artesunat-Amodiakuin dibandingkan dengan Sulfadoksin-Pirimetamin dan Primakuin pada penderita malaria falciparum tanpa komplikasi di Kabupaten Purworejo

KUSUMANINGSIH, Marti, Prof.dr. Soesanto Tjokrosonto, M.Sc.,Ph.D

2005 | Tesis | S2 Ilmu Kedokteran Tropis

Malaria masih merupakan problem kesehatan di Purworejo. Salah satunya hambatan pada pencegahan malaria termasuk manajemen kasus. Klorokuin masih merupakan obat antimalaria standar atau lini ke-1 dalam pengobatan malaria vivax di Indonesia. Memperbaiki resistensi P.falciparum terhadap pengobatan standar menjadi salah satu penyulit dalam pemberantasan malaria, terutama pada penduduk didaerah endemis. Untuk mengatasi problem tersebut, obat antimalaria baru seperti artesunatamodiakuin di teliti dan dibandingkan dengan obat standar (lini ke-2) sulfadoksin-pirimetamin dan primakuin. Penelitian ini adalah eksperimen lapangan dengan menggunakan metode uji acak terkontrol. Tujuan penelitian menilai efikasi obat artesunat-amodiakuin dibandingkan dengan sulfadoksinpirimetamin dan primakuin pada pasien malaria falciparum tanpa komplikasi. Enam puluh tiga subyek penelitian didapat melalui Active Case Detection (ACD) dan Passive Case Detection (PCD) dari bulan Juni 2004 sampai Januari 2005 di wilayah Puskesmas Gebang, Bruno, Bener, Loano, Winong. Subyek adalah penderita malaria falciparum tanpa komplikasi dengan kriteria inklusi usia ≥5 tahun, P.falciparum aseksual tunggal dengan kepadatan parasit > 400/μl darah, tanpa gametosit, tidak hamil, tidak menderita malaria berat atau dengan komplikasi, tidak ada riwayat alergi terhadap sulfadoksin-pirimetamin, primakuin, artesunat-amodiakuin dan bersedia berpartisipasi dalam studi selama 28 hari dengan mengisi informed consent. Subyek penelitian secara random dibagi dalam 2 group pengobatan, pertama menerima artesunat-amodiakuin, kedua menerima sulfadoksin-pirimetamin + primakuin. Hasil pengobatan dinilai melalui respon pengobatan, pembentukan gametosemia dan efek samping. Evaluasi meliputi 63 subyek yang dibagi dalam 2 group pengobatan. Sekitar 11 subyek drop-out . Respon pengobatan ACPR( respon klinis dan parasit memadai) pada hari ke-14/28 kombinasi artesunat-amodiakuin, sulfadoksin-pirimetamin + primakuin sebesar 93,5%/87,1%; 90,1%/78,1%, dan ETF ( kegagalan terapi dini) adalah 0/0; 3,1%/3,1%, LCF ( kegagalan klinis kasep) adalah 3,2%/6,5% dan LPF ( kegagalan parasitologi kasep) adalah 3,2%/6,5%; 3,1%/12,5%. Secara uji statistik hasil tersebut tidak ada perbedaan bermakna (p> 0,05). Rata-rata angka penurunan panas (FCT) pada kelompok artesunat-amodiakuin adalah 31,74 ± 11,40 jam, sedangkan kelompok sulfadoksinpirimetamin + primakuin adalah 44,25 ± 19,38 jam. Rata-rata penurunan parasit pada kelompok artesunat-amodiakuin adalah 1,3 ±0,47 hari, sedangkan kelompok sulfadoksin-pirimetamin + primakuin adalah 2,48 ± 0,92 hari. Evaluasi gametosemia sampai hari ke-28 pada kelompok artesunat-amodiakuin dan sulfadoksin-pirimetamin + primakuin adalah 9,6%/15,6%.Efek samping yang terjadi pada kelompok artesunat-amodiakuin dan sulfadoksin-pirimetamin + primakuin adalah mual 25,8%/18,7% ;lemah sekitar 25,8%/12,5%; muntah sekitar 9,7%/3,1%; sakit ulu hati sekitar 12,9%/3,1%; gatal 3,2%/0; sakit kepala 22,5%/12,5%; sulit tidur sekitar 6,5%/0 dan pulih kembali tanpa pengobatan. Efikasi obat kombinasi artesunat-amodiakuin adalah sama dengan obat sulfadoksin-pirimetamin + primakuin. Waktu penurunan panas dan waktu menghilangmya parasit obat artesunat-amodiakuin lebih cepat daripada kelompok pengobatan sulfadoksin-pirimetamin + primakuin.

Malaria is still a Public Health problem in Purworejo district. One of obstacles in malaria prevention including case management. Chloroquine is still gold standard anti-malaria or first line anti malaria drug for treatment P.vivax in Indonesia. Improved resistance P.falciparum toward standard medications turns out to be one of difficulties in malaria prevention, specifically among endemic areas. To solve the problem, a new anti-malaria drugs i.e. artesunate-amodiaquine has been and is being examined compared by a standart anti-malaria drug (second lini) sulfadoxinepyrimethamine and primaquine. The study was field experimental using a randomized controlled trial approach. The objective of this study is to investigate the efficasious of artesunate-amodiaquine therapy compared sulfadoxinepyrimethamine and primaquine therapy for uncomplicated falciparum malaria patients. Sixty-three subjects were recruited through Active Case Detection (ACD) and Passive Case Detection (PCD) from June 2004 to January 2005 at area of Gebang, Bener, Bruno, Winong, and Loano Primary Health Care, Purworejo ; the subjects were falciparum malaria uncomplicated whose their inclusion criteria were age ≥ 5 years old, asexual P.falciparum > 400/ul blood, no gametocyte, not pregnant, not having complication of malaria or severe malaria, no history to allergy sulfadoxine-pyrimethamine, primaquine, artesunate-amodiaquine . and were willing to participate in 28 days-study by signing informed consent forms, were included in this study. Subjects were randomly divided into two groups of treatment, the first was given combination artesunateamodiaquine, the second was given combination sulfadoxine-pyrimethamine and primaquine. The medicine evaluation was treated by measuring the response of treatment, gametocytemia produce and side effect . Evaluation was performed on 63 subjects divided into two groups. Among eleven subjects were drop out. The testing results on evaluation on day 14/28 showed that ACPR of combination artesunate-amodiaquine, combination sulfadoxine-pyrimethamine and primaquine were 93,5%/ 87,1%, 90,1%/ 78,1%.and failed therapy ETF were 0/0, 3,1%/3,1% , LCF were 3,2%/6,5% and LPF were 3,2%/6,5% , 3,1%/12,5% , respectively. This value was not significantly different (p> 0,05). Average rate of Fever Clearance Time (FCT) in artesunate-amodiaquine group were 31,74± 11,40 hours, while sulfadoxine-pyrimethamine and primaquine were 44,25 ± 19,38 hours .Average rate of Parasite Clearance Time (PCT) in artesunate-amodiaquine group were 1,3± 0,47 days, while sulfadoxine-pyrimethamine and primaquine were 2,48 ± 0,92 days. Evaluation on gametocytemia on day 28 were 9,6%/ 15,6% respectively. In addition, side effects perceived among artesunateamodiaquine group and sulfadoxine-pyrimethamine group involved nausea among 25,8% / 18,7% subjects, malaise among 25,8%/12,5% subjects, vomiting among 9,7%/3,1% subjects, abdominal pain among 12,9%/3,1% subjects, itching among 3,2%/0 subject, headache among 22,5%/12,5%, insomnia among 6,5%/0 subjects and they recovered no treatment. It could be concluded that treatment using artesunate-amodiaquine drugs provided efficasious (87,1%) similar with sulfadoxine-pyrimetamine and primaquine (78,1%) but fever clearance time (FCT) and parasite clearance time (PCT) more faster than other group. There were no serious in clinical side effects caused by the two regiments founds in this study.

Kata Kunci : Epidemiologi Malaria,Respon Terapi,Artesunat,Amodiakuin, P.falciparum, efficacy, respon’s therapy, artesunate-amodiaquine and sulfadoxinepyrimethamine + primaquine