Opportunities For Evaluating Malaria Vaccines In Indonesia

Di Indonesia, khususnya di Irian Jaya dan daerah malaria tinggi lainnya terdapat kesempatan yang sangat baik untuk mengevaluasi vaksin malaria. Hal ini antara lain disebabkan tersedianya data epidemiologi termasuk insidens, risiko malaria yang tinggi dan merata pada berbagai kelompok umur, jenis kelamin dan pekerjaan, adanya kelompok masyarakat yang sesuai untuk penelitian (transmigran dan angkatan bersenjata), lokasi desa yang memungkinkan randomisasi serta tersedianya fasilitas laboratorium di dekat daerah penelitian. Pemberantasan malaria dengan vaksinasi diharapkan akan menjadi fokus dari penelitian kesehatan menjelang akhir abad ke-20. Indonesia yang terdiri dari berbagai pulau memungkinkan konsolidasi pemberantasan malaria secara bertahap. Pengalaman yang diperoleh dengan pemberantasan malaria di suatu pulau akan sangat bermanfaat untuk menghadapi masalah yang lebih berat yakni malaria di daratan luas seperti Afrika atau daratan Asia Tenggara

Mefloquine Is Highly Efficacious against Chloroquine-Resistant \u3ci\u3ePlasmodium vivax\u3c/i\u3e Malaria and \u3ci\u3ePlasmodium falciparum\u3c/i\u3e Malaria in Papua, Indonesia

Background. During the period of 1996–1999, we prospectively monitored 243 Javanese adults and children after arriving in Papua, Indonesia, and microscopically documented each new case of malaria by active surveillance. Methods. In a randomized, open-label, comparative malaria treatment trial, 72 adults and 50 children received chloroquine for each incident case of malaria, and 74 adults and 47 children received mefloquine. Results. Among 975 primary treatment courses, the cumulative 28-day curative efficacies were 26% and 82% for chloroquine against Plasmodium falciparum malaria and Plasmodium vivax malaria, respectively. Mefloquine cure rates were far superior (96% against P. falciparum malaria and 99.6% against P. vivax malaria). Conclusions. Mefloquine is a useful alternative treatment for P. vivax malaria and P. falciparum malaria in areas such as Papua, where chloroquine is still recommended as the first-line therapeutic agent

Failure of Supervised Chloroquine and Primaquine Regimen for the Treatment of Plasmodium vivax in the Peruvian Amazon

The widespread use of primaquine (PQ) and chloroquine (CQ), together, may be responsible for the relatively few, isolated cases of chloroquine-resistant P. vivax (CQRPV) that have been reported from South America. We report here a case of P. vivax from the Amazon Basin of Peru that recurred against normally therapeutic blood levels of CQ. Four out of 540 patients treated with combination CQ and PQ had a symptomatic recurrence of P. vivax parasitemia within 35 days of treatment initiation, possibly indicating CQ failure. Whole blood total CQ level for one of these four subjects was 95 ng/ml on the day of recurrence. Based on published criteria that delineate CQRPV as a P. vivax parasitemia, either recrudescence or relapse, that appears against CQ blood levels >100 ng/mL, we document the occurrence of a P. vivax strain in Peru that had unusually high tolerance to the synergistic combination therapy of CQ + PQ that normally works quite well

Treatment of Chloroquine-Resistant \u3ci\u3ePlasmodium vivax\u3c/i\u3e with Chloroquine and Primaquine or Halofantrine

Optimal therapy gor infection by chloroquine-resistant Plasmodium vivax has not been established. From 1992 to 1994 during three separate studies, 147 Javanese residents of Irian Jaya infected by P. vivax were treated with either chloroquine (2 5 mg of base/kg during 3 days or 10mg of base/kg in one dose) plus primaquine (1 0 mg/kg during 28 days or 2.5 mg/kg during 3 days)( n = 78), chloroquine plus placebo( n = 50), or halofantrine (24 mg base/kg in 12 h; n = 19). There was no difference in tolerance to or side effects of any of the regimens. Within 14 days of starting therapy, therapeutic failure among these patients was 44% for chloroquine, 5% for chloroquine plus primaquine (P \u3c .001), and 0 for halofantrine (P \u3c .001). After 28 days, therapeutic failure was 78%, 15%, and 6% respectively. Thus, chloroquine plus primaquine in combination and halofantrine alone are effective therapies for chloroquine-resistant P. vivax

A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Tafenoquine for Weekly Prophylaxis against \u3ci\u3ePlasmodium falciparum\u3c/i\u3e

Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for malaria prophylaxis in nonpregnant persons with normal glucose-6-phosphate dehydrogenase (G6PD) function. A randomized, doubleblind, placebo-controlled chemoprophylaxis trial was conducted with adult residents of northern Ghana to determine the minimum effective weekly dose of tafenoquine for the prevention of infection by Plasmodium falciparum. The primary end point was a positive malaria blood smear result during the 13 weeks of study drug coverage. Relative to the placebo, all 4 tafenoquine dosages demonstrated significant protection against P. falciparum infection: for 25 mg/week, protective efficacy was 32% (95% confidence interval [CI], 20%–43%); for 50 mg/week, 84% (95% CI, 75%–91%); for 100 mg/week, 87% (95% CI, 78%–93%); and for 200 mg/week, 86% (95% CI, 76%–92%). The mefloquine dosage of 250 mg/week also demonstrated significant protection against P. falciparum infection (protective efficacy, 86%; 95% CI, 72%–93%). There was little difference between study groups in the adverse events reported, and there was no evidence of a relationship between tafenoquine dosage and reports of physical complaints or the occurrence of abnormal laboratory parameters. Tafenoquine dosages of 50, 100, and 200 mg/week were safe, well tolerated, and effective against P. falciparum infection in this study population

Clinical Laboratory Parameters Among Adult Males During a Primaquine Chemoprophylaxis Trial in Irian Jaya, Indonesia

Primakuin yang digunakan sebagai profilaksis malaria terbukti efektif dan diterima dengan baik oleh tubuh manusia yang normal terhadap aktivitas enzim 6 glukosa-6 fosfat dehidrogenase (G-6PD). Pemeriksaan laboratoris klinik adalah bagian dari uji coba secara acak dengan kontrol plasebo dalam rangka mengevaluasi penggunaan primakuin sebagai profilaksis pada penduduk transmigran yang tidak kebal di Irian Jaya. Penelitian ini dilakukan terhadap 129 pria Jawa dewasa yang normal G-6PDnya. Pemeriksaan hematologi, fungsi hati dan ginjal, dan pemeriksaan limfosit dilakukan berulang kali selama waktu penelitian profilaksis dilakukan untuk menjamin keamanan dari sukarelawan tersebut dan mengawasi Perubahan yang mungkin terjadi akibat obat profilaksis. Seperti yang diperkirakan, pengguna primakuin tidak menunjukkan gejala peningkatan methemoglobin yang kembali dalam batas normal setelah 7 hari pemberian dosis terakhir. Pada akhir penelitian (12 bulan profilaksis) nilai hematologi, fungsi hati dan ginjal, dan nilai limfosit dari kelompok primakuin sebanding dengan kelompok plasebo, dan berada dalam batas nilai normal untuk orang Indonesia.Hasil penelitian ini memberikan masukan adanya keluhan fisik yang sedikit dari sukarelawan pengguna profilaksis primakuin. Untuk membuktikan hasil penelitian ini dan mempersiapkan penggunaan secara umum primakuin untuk profilaksis malaria, perlu dilakukan uji coba lebih lanjut keamanan primakuin. Di Indonesia, primakuin tidak digunakan sebagai profilaksis dan laporan hasil penelitian ini hendaknya tidak ditafsirkan sebagai laporan keamanan dari primakuin

Changes in the total leukocyte and platelet counts in Papuan and non Papuan adults from northeast Papua infected with acute Plasmodium vivax or uncomplicated Plasmodium falciparum malaria

<p>Abstract</p> <p>Background</p> <p>There are limited data on the evolution of the leukocyte and platelet counts in malaria patients.</p> <p>Methods</p> <p>In a clinical trial of chloroquine vs. chloroquine plus doxycycline vs. doxycycline alone against <it>Plasmodium vivax </it>(n = 64) or <it>Plasmodium falciparum </it>(n = 98) malaria, the total white cell (WCC) and platelet (PLT) counts were measured on Days 0, 3, 7 and 28 in 57 indigenous Papuans with life long malaria exposure and 105 non Papuan immigrants from other parts of Indonesia with limited malaria exposure.</p> <p>Results</p> <p>The mean Day 0 WCC (n = 152) was 6.492 (range 2.1–13.4) × 10⁹/L and was significantly lower in the Papuans compared to the non Papuans: 5.77 × 10⁹/L vs. 6.86 × 10⁹/L, difference = -1.09 [(95% CI -0.42 to -1.79 × 10⁹/L), P = 0.0018]. 14 (9.2%) and 9 (5.9%) patients had leukopaenia (<4.0 × 10⁹/L) and leukocytosis (>10.0 × 10⁹/L), respectively. By Day 28, the mean WCC increased significantly (P = 0.0003) from 6.37 to 7.47 × 10⁹/L (73 paired values) and was similar between the two groups. Ethnicity was the only WCC explanatory factor and only on Day 0.</p> <p>The mean Day 0 platelet count (n = 151) was 113.0 (range 8.0–313.0) × 10⁹/L and rose significantly to 186.308 × 10⁹/L by Day 28 (P < 0.0001). There was a corresponding fall in patient proportions with thrombocytopaenia (<150 × 10⁹/L): 119/151 (78.81%) vs. 16/73 (21.92%, P < 0.00001). Papuan and non Papuan mean platelet counts were similar at all time points. Only malaria species on Day 0 was a significant platelet count explanatory factor. The mean D0 platelet counts were significantly lower (P = 0.025) in vivax (102.022 × 10⁹/L) vs. falciparum (122.125 × 10⁹/L) patients.</p> <p>Conclusion</p> <p>Changes in leukocytes and platelets were consistent with other malaria studies. The Papuan non Papuan difference in the mean Day 0 WCC was small but might be related to the difference in malaria exposure.</p

New Haplotypes of the \u3ci\u3ePlasmodium falciparum\u3c/i\u3e Chloroquine Resistance Transporter (\u3ci\u3ePFCRT\u3c/i\u3e) Gene Among Chloroquine-Resistant Parasite Isolates

Mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene were examined to assess their associations with chloroquine resistance in clinical samples from Armopa (Papua) and Papua New Guinea. In Papua, two of the five pfcrt haplotypes found were new: SVIET from Armopa and CVIKT from an isolate in Timika. There was also a strong association (P \u3c 0.0001) between the pfcrt 76T allele and chloroquine resistance in 50 samples. In Papua New Guinea, mutations in the pfcrt gene were observed in 15 isolates with chloroquine minimum inhibitory concentrations (MICs) of 16−64 pmol, while the remaining six isolates, which had a wild-type pfcrt gene at codon 76, had MICs of 2−8 pmol. These observations confirm that mutations at codon 76 in the pfcrt gene are present in both in vivo and in vitro cases of chloroquine resistance, and that detection of the pfcrt 76T allele could predict potential chloroquine treatment failures

Atovaquone/Proguanil Therapy for \u3ci\u3ePlasmodium falciparum\u3c/i\u3e and \u3ci\u3ePlasmodium vivax\u3c/i\u3e Malaria in Indonesians Who Lack Clinical Immunity

Thirty-eight of 295 subjects participating in a randomized, double-blind, placebo-controlled trial of the efficacy of daily administration of atovaquone/proguanil for malaria prevention developed malaria at some time during the 20-week prophylaxis period. These subjects (3 atovaquone/proguanil recipients and 35 placebo recipients) were treated with 4 tablets of atovaquone/proguanil per day for 3 days. Atovaquone/proguanil provided safe, well-tolerated, and effective therapy for uncomplicated malaria in nonimmune Indonesians

Virus isolations and high population density implicate \u3ci\u3eCulex antennatus\u3c/i\u3e (Becker) (Diptera: Culicidae) as a vector of Rift Valley Fever virus during an outbreak in the Nile Delta of Egypt

In June, 2003, Egypt’s hospital-based electronic disease surveillance system began to record increased cases of acute febrile illness from governorates in the Nile Delta. In response to a request for assistance from the Egyptian Ministry of Health and the World Health Organization (WHO), the U.S. Naval Medical Research Unit No. 3 (NAMRU-3) provided assistance in identifying the cause and extent of this outbreak. Testing of human clinical samples (n = 375) from nine governorates in Egypt identified 29 cases of RVF viremia that spanned the period of June to October, and a particular focus of disease in Kafr el Sheikh governorate (7.7% RVF infection rate). Veterinary samples (n = 101) collected during this time in Kafr el Sheikh and screened by immunoassay for RVFV-specific IgM identified probable recent infections in cattle (10.4%) and sheep (5%). Entomologic investigations that focused in rural, rice growing villages in the Sidi Salim District of Kafr el Sheikh during August–September, 2003, collected, identified, and tested hostseeking female mosquitoes for the presence of pathogenic viruses. Three isolates of RVF virus (RVFV) were obtained from 297 tested pools of female mosquitoes and all three RVFV isolates came from Cx. antennatus (Becker). While Cx. pipiens has been considered the primary vector of RVF virus in Egypt and is often the most common man-biting species found, Cx. antennatus was the dominant species captured at the 2003 outbreak location in Kafr el Sheikh governorate. This is the first time that Cx. antennatus has been found naturally infected with RVFV in Egypt