Pengobatan Malaria dengan Kombinasi Artemisinin

Previous approaches in malaria treatment fail to reduce the morbidity and mortality of malaria. Widespread overuse of antimalarial treatment of clinical malaria may have contributed to increase drug resistance. Moreover, poor compliance or inadequate dosage also selects for parasite resistance. The paradigm of radical treatment using drug combinations may improve the cure rate and compliance, thereby preventing or delaying the emergence of parasites resistant to antimalarial drugs. The ideal combined antimalarial regimen in Indonesia should be safe and tolerated by all age groups, effective and rapidly acting for both P.falciparum and P.vivax malaria, short course, good compliance and acceptable, without resistance and/or cross-resistance or , not widely spread use, cost-effective and affordable. Artemisinin derivatives are the best partner drug for combination, with advantages that include: well absorbed, safe and well tolerated, rapidly converted to active metabolite, having very short half-life, broad specificity of action, and extremely potent. Current artemisinin-based combinations which are suitable for Indonesia include: amodiaquine plus artesunate given as single daily dose for 3 days (AQ3+ATS3), mefloquine plus artesunate given as single daily dose for 3 days (MQ3+ATS3), lumefantrine/benflumetol plus artemether given as twice daily dose for 3 days (COARTEMETHER), piperaquine plus dihydroartemisinin given as single daily dose for 2-3 days (PPQ2-3+DHA2-3), and piperaquine plus artemisinin given as single daily dose for 2 days (PPQ2+ATM2). Given the imbalance between rapid development of parasite resistance and slow availability of new effective antimalarial drugs, research and development of antimalarial drugs must be encouraged

Tinjauan Hasil Uji Coba Pengobatan Dan Pencegahan Malaria Di Beberapa Tempat Indonesia, 1986- 1995

In Indonesia, only antimalarials chloroquine, sulfadoxine/ sulfalene-pyrimethamine, quinine, and primaquine are available. The development of chloroquine and multidrug resistance poses a therapeutic challenge. In order to obtain alternative antimalarial drugs, trials were conducted of malaria treatment and prophylaxis in several chloroquine or multidrug resistance areas. The objective of these trials was to assess the efficacy and safety of the alternative antimalarial drugs. All the trials were mostly open studies in the fields and hospitals. These were collaboration studies between Communicable Disease Research Center, Communicable Disease Control and Environmental Health, Faculty of Medicine of the University of Indonesia, NAMRU-2, and local health staff. The patients were selected according to the WHO criteria for in-vivo antimalarial drug sensitivity testing. They should sign the informed consent form and they were followed up during the study, for 2 weeks - 4 months. In chloroquine and multidrug resistance areas, mefloquine, halofantrine, and artemether are effective and safe for treatment of uncomplicated falciparum malaria. While artesunate was noted effective and safe only in the first 14 days. Halofantrine was also documented effective and safe for vivax malaria treatment. Intramuscular artemether was effective and safe for treatment of severe and complicated falciparum malaria, particularly in remote areas lacking hospitals and the capability for intravenous infusion. Primaquine, doxycycline and mefloquine are effective and safe for malaria prophylaxis. Since the new antimalarials are not yet available in Indonesia, the improvement of efficacy of antimalarial drugs currently available should be studied. Prophylactic drugs which are effective and safe for children, pregnant and lactating women should also be studied

Confirmation of Plasmodium Falciparum Treatment Failure Cases by Polymerase Change Reaction Genotyping

Background: Treatment failure in clinical trial, may be caused by P. falciparum resistant to antimalarialdrug. This study aimed to confirm the treatment failure cases of P. falciparum whcther caused byrecrudescence / resistant or new infection of different strain parasite.Methods: This study was a part of the activity in antimalarial drug efficacy trials (artemisinin-naphthoquine/AN versus dihydroartemisinin – piperaquine/DHP). P. falciparum infections on failure cases weregenotyped for allelic variation in those 3 markers by comparing before (D0) and after treatment (DF) ifparasites recurrent with nested polymerase change reaction (PCR).Results: Thirteen of 19 P. falciparum failure cases showed PCR genotyping completely successful 100%for MSP1 (D0 & DF), MSP2 (DF) and GLURP (D0) and the lowest (76,9% ) for GLURP (DF). Whenall 3 genes were combined, the amplification result showed 69.2%. Identification allele for each locusgenes shown that MSP1 had just one (D0 or DF). Conversely, for MSP2 and GLURP, there were someadditional alleles either at D0 and DF. By comparing the pattern of genotype (alleles) P. falciparum atD0 and DF each locus genes, the confirmation of P. falciparum resistant from new infection could bedetermined The proportion of recrudescence and new infection almost the same, 8 of 13 failed cases werefrom artemisinin-naphthoquine (AN) group.Conclusion: The confirmation of P. falciparum by comparing genotype at D0 and DF could determine parasiteresistant and new infection from treatment failure cases. Recrudescence occurred within 17 days after treatmentand new infection occurred >28 days after treatment. (Health Journal of Indonesia. 2015;6:29-37

Faktor Risiko Penyakit Ginjal Kronik : Studi Kasus Kontrol Di Empat Rumah Sakit Di Jakarta Tahun 2014

A case control study was conducted in four government hospitals in Jakarta according to KidneyDisease Improving Global Outcome (KDIGO) 2012 criteria, in the last 10 years. Control subjectswere diagnosed as not CKD based on estimating glomerulus filtration rate (e-GFR) of ≥60ml /minute/1.73m2 and normal urinalysis test. Data were collected by interviewing with subjects usingstructured questionnaires. Laboratory test results were extracted from the medical records orretested laboratory results of serum creatinine, HbA1c, and urinalysis at screening and enrollmenttime. A total of 429 eligible subjects in each group were analysed by logistic regression. Age, familyhistory of CKD, plain water consumption ≤2000ml/day, carbonated drink consumption, energy drinkconsumption, history of kidney diseases, kidney stone, hypertension, and diabetes mellitus increasedrisk of CKD with adjusted odds ratio range from 1.8 to 25.8. Consumption of coffee, tea, chocolate,alcohol drinks, non-steroid anti-inflammatory drug (NSAID), traditional herbal for musculoskeletaldisorder or obesity, smoking, and less quality of drinking water were not significantly associatedwith CKD. It concluded that risk factors of CKD were everyday consumption of carbonated drinkand energy drink

Artesunat-amodiakuin dan Klorokuin untuk Pengobatan Malaria Vivaks di Puskesmas Kopeta, Maumere, Nusa Tenggara Timur, 2007

Indonesia merupakan negara endemis malaria yang merekomendasi Artemisinin-based Combination Therapy (ACT) untuk malaria Plasmodium vivax. Konfirmasi resistensi P.vivax terhadap kloroquin dan efikasi ACT perlu diteliti untuk mendukung kebijakan pengobatan malaria. Provinsi Papua bersama Nusa Tenggara Timur (NTT) penyumbang utama kasus malaria di Indonesia. Tujuan penelitian untuk mengevaluasi efikasi dan keamanan ACT program artesunat-amodiakuin (AsAq) dibandingkan obat konvensional klorokuin (Cq) pada malaria vivaks di Puskesmas, Provinsi NTT. Penelitian ini merupakan penelitian klinis, prospektif, evaluasi efikasi dan keamanan AsAq dibandingkan Cq pada subyek P.vivax malaria dan diamati selama 28 hari, sesuai protokol WHO tahun 2003. Efikasi AsAq dan Cq dianalisis dan dibandingkan secara intention to treat (ITT) dan per protocol (PP). Keamanan obat dievaluasi berdasarkan timbulnya atau memberatnya gejala klinis dalam kurun waktu 28 hari. Total 100 subjek monoinfeksi P. Vivax yang memenuhi criteria diobati secara acak dengan AsAq atau Cq. Efikasi hari-28 AsAq dibandingkan Cq secara Intention to Treat (ITT) adalah 93,7% (95%CI: 83,8 97,9) versus 56,4% (95%CI: 50,1 75,9) dengan Log Rank (Mantel Cox)<0.001 dan Hazard Ratio 8,3 (95%CI: 2,4 28,2). Efikasi hari-28 AsAq per protocol (PP) adalah 93,6% (95%CI: 82,8 97,8) dibandingkan Cq51,4% (95%CI: 35,9 66,6) dengan Log Rank (Mantel Cox)<0,001 dan HR 9,3 (95%CI: 2,7 31,7). Dua (4%) kasus dengan Cq mengalami kegagalan pengobatan dini (Early Treatment Failure) di hari-3. Kejadian sampingan terbanyak AsAq dan Cq adalah muntah (26% vs 20,4%)dan dua kasus pengobatan Cq merupakan kasus kejadian sampingan serius karena muntah berulang yang memerlukan rawat inap. Efikasi AsAq lebih baik secara signifikan dibandingkan Cq untuk pengobatan P. Vivax di Maumere. Muntah merupakan kejadian sampingan AsAq dan Cq yang paling sering terjadi dan memerlukan pengobatan. ACT alternatif yang efektif dan aman dibutuhkan untuk pengobatan infeksi P. vivax.Kata kunci : artesunat, amodiakuin, klorokuin, P. vivax.AbstractIndonesia as a malaria endemic country is recommended to use Artemisinin-based Combination Therapy (ACT) for P. vivax malaria. Confirmation of Chloroquine resistant and ACT efficacy for P. vivax need to be investigated for supporting malaria treatment policy. Papua and East Nusa Tenggara (NTT) contribute the main malaria cases in Indonesia. To evaluate efficacy and safety of ArtesunateAmodiaquine (AsAq) as an ACT programme compared to drug Klorokuin (Cq) as a conventional for vivax malaria at Public Health Care in NTT. This was a clinical study, prospective, efficacy and safety evaluation of AsAq compared to Cq for malaria P.vivax subject and followed by 28 days, based on WHO protocol 2003. Intention to treat (ITT) and per protocol (PP) was performed to compare AsAq and Cq efficacy. Safety was evaluated based on the incidance or severity of clinical symptoms by 28 days of follow up. Total of 100 P. vivax monoinfection suitable with the inclusion/exclusion criteria was randomized treated with AsAq or Cq. The 28 days efficacy of AsAq and Cq was 93.7% (95%CI: 83.8 97.9) versus 56.4% (95%CI: 50.1 75.9) with Log Rank (Mantel Cox)<0.001 and Hazard Ratio (HR) 8,3 (95%CI: 2,4 28,2) by intention to treat (ITT). Per protocol (PP) efficacy was 93.6% (95%CI: 82.8 97.8) compared toCq51.4% (95%CI: 35.9 66.6), Log Rank (Mantel Cox) <0,001 and HR 9,3 (95%CI: 2,7 31,7). Two (4%) cases with Cq had early treatment failure (ETF) at day 3. The major adverse event was vomiting for both AsAq and Cq (26% vs 20,4%) and two cases with severe vomiting were hospitalized. The efficacy of AsAq was better significantly than Cq for P. vivax treatment in Maumere. Vomiting was the major adverse event for both drugs and needed a treatment. The alternative of effective and safety ACT is needed for P. vivax infection.Key word : artesunate, amodiaquine, choloquine, P. vivax

Keragaman Genetik Petanda P. Falciparum dari Specimen Subyek Penelitian Monitoring Dihidroartemisinin-piperakuin di Kalimantan dan Sulawesi

Treatment failure in falciparum malaria may be caused by parasite resistant to antimalarial drug or new infection. Polymorphism genetic marker of P. falciparum namely MSP1, MSP2 and GLURP locus genes in the population should be identified as a baseline to distinguish the cause of treatment failure. A nested Polymerase Chain Reaction (PCR) method was applied to each locus gene separately. A total 121 dried blood spot specimens from subjects infected with P. falciparum in monitoring Dihydroartemisinin-Piperaquine treatment in Kalimantan and Sulawesi Islands were analyzed. Locus genes of MSP1, MSP2 and GLURP were successful identified 82.6%, 96.7% and 81.0% respectively. However, the three (MSP1, MSP2 and GLURP) locus genes were only found in 71.9% (87 of 121) samples. All of MSP1 locus gene had just one allele, two alleles on most of MSP2 (67.5%) and few of GLURP (14.3%). Multi genotype infection was likely dominant than a single genotype infection (65.5% vs. 34.5%). Based on allele length classification, MSP2 locus gene shows more variety of allele class (12 alleles) than GLURP (9 alleles) and MSP1 (7 alleles), with an allele length mostly for MSP1: 440 - 479 bp, MSP2: 480–519 bp and GLURP: 580–639 bp. In this study, falciparum malaria cases were commonly as multi-genotype infection, and MSP2 was a dominant and polymorphic genetic marker of P.falciparum. Keywords: P. falciparum, PCR, MSP1, MSP2, GLURP, allele Abstrak Gagal pengobatan pada malaria falsiparum dapat disebabkan oleh parasit yang resisten terhadap obat antimalaria atau oleh infeksi baru. Keragaman genetik petanda Plasmodium falciparum yaitu lokus gen MSP1, MSP2 dan GLURP dalam suatu populasi perlu diidentifikasi sebagai dasar untuk membedakan penyebab gagal pengobatan. Metode pemeriksaan yang digunakan adalah nested Polymerase Chain Reaction (PCR) terhadap masing-masing lokus gen secara terpisah. Telah dianalisis 121 spesimen resapan darah kering pada kertas filter dari subyek terinfeksi P.falciparum pada studi monitoring pengobatan dengan Dihidroartemisinin-Piperakuin di Kalimantan dan Sulawesi. Masing-masing lokus gen MSP1, MSP2 dan GLURP yang dapat diidentifikasi sebanyak 82,6%, 96,7% and 81,0%. Sedangkan ketiga lokus gen tersebut ditemukan hanya pada 71,9% (87/121) sampel. Lokus gen MSP1 semuanya mempunyai 1 alel, sedangkan dua alel ditemukan pada sebagian besar MSP2 (67,5%) dan sebagian kecil GLURP (14,3%). Infeksi multi-genotip oleh dua atau lebih genotip P.falciparum ditemukan pada 65,5% sampel dan infeksi tunggal hanya 34,5% sampel. Keragaman klas alel paling banyak ditemukan pada lokus gen MSP2 sebanyak 12 klas alel, GLURP sebanyak 9 klas alel, dan MSP1 sebanyak 7 klas alel. Alel pada lokus gen MSP1 sebagian besar pada kisaran 440 - 479 bp, MSP2: 480 – 519 bp, dan GLURP: 580–639 bp. Pada penelitian ini kasus malaria falsiparum umumnya merupakan infeksi multi-geotip, dan MSP2 merupakan petanda gen P.falciparum yang dominan dan beragam. Kata kunci : P. falciparum, PCR, MSP1, MSP2, GLURP, ale

Antimalarial Drug Evaluations: Namru-2 And Indonesian Partnership

Meningkatnya insiden malaria di beberapa daerah tertentu terutama di Indonesia Bagian Timur disebabkan antara lain : P. falciparum telah resisten terhadap beberapa obat antimalaria, ditemukannya P. vivax resisten klorokuin, dan belum tersedianya vaksin yang efektif. Sehubungan dengan hal tersebut, dilakukanlah evaluasi obat antimalaria yang perlu dipertimbangkan dalam peningkatan pelaksanaan program. Obat antimalaria meflokuin, halofantrin dan beberapa derivat qinghaosu (artesunat dan artemeter) telah diuji coba klinik di Indonesia, dan memberikan efikasi yang cukup baik walaupun perlu dipertimbangkan kemungkinan efek samping dan resistensi atau rekrudesensi yang mungkin terjadi serta harganya yang relatif masih mahal. Obat antimalaria baru yang direncanakan akan diuji coba klinik adalah azithromycin, derivat primaquine WR 238605, atovaquone dan derivat qinghaosu lain. Dasar pengembangan pengobatan malaria adalah sebagai berikut: Meningkatkan atau memperbaiki efikasi pengobatan malaria tanpa komplikasi yaitu dengan mengembangkan kombinasi atau regimen obat antimalaria yang tersedia di Indonesia (klorokuin dan tetrasiklin/doksisiklin) atau dengan mempersiapkan obat antimalaria baru (derivat qinghaosu, atovaquone, azithromycin dan WR 238605).Mencari obat antimalaria baru alternatif yang efektif sebagai obat penyelamat untuk pengobatan malaria dengan komplikasi. Dengan melakukan evaluasi obat antimalaria ini, akan didapat data efikasi dan keamanan yang dapat membantu Departemen Kesehatan untuk menentukan obat pilihan di Indonesia. Selain itu juga dapat ikut membantu menanggulangi masalah malaria di dunia

Leukopenia Sebagai Prediktor Terjadinya Sindrom Syok Dengue Pada Anak Dengan Demam Berdarah Dengue Di Rspi. Prof. Dr. Sulianti Saroso

The development of DHF patient usually assessed base on clinical condition, platelet count and haematocrit value as the DSS indicators. While leukocyte count is irrespective though leucopenia is common in viral infection. Therefore, further analysis was run to determine whether leucopenia could be as a predictor of DSS This study was a retrospective study with a case control (1:2) design using hospitalized children medical records from January 2006 to April 2008 at Prof. Dr. Sulianti Saroso Infectious Diseases Hospital. DSS cases were purposive sampling, and DHF controls were selected using simple random sampling. There were 43 children diagnosed as DSS, and 86 diagnosed as DHF. By multivariate analysis, DHF subjects with leucopenia showed 2.9 times higher risk to develop DSS than DHF subjects without leucopenia. ( 95% CI: 1.2-6.6). Increasing hematocrite was found as a confounding variable with (ORa: 4.0 ; 95% CI: 1.7-9.5). As conclusion, leucopenia could be a predictor of progression DHF to DSS