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

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

Short Report: Therapeutic Efficacy of Chloroquine Combined with Primaquine Against \u3ci\u3ePlasmodium falciparum\u3c/i\u3e in Northeastern Papua, Indonesia

Chloroquine combined with primaquine was evaluated for therapy of uncomplicated malaria caused by Plasmodium falciparum in nonimmune Javanese migrants to northeastern Papua, Indonesia. Subjects were randomized to treatment with standard chloroquine therapy (25 mg/kg in 3 doses over the course of 48 hours) with 30 mg primaquine administered daily for 28 days (n = 25) or a placebo of primaquine (n = 28). The 14-day cumulative incidence of therapeutic failure was 56% with primaquine and 79% with placebo (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.1–1.3; P = 0.08). Primaquine administered daily created a marginally significant improvement in therapeutic efficacy at day 14, but not at day 7 (20% versus 36%; OR, 0.2; 95% CI, 0.1–1.8; P = 0.2) or day 28 (82% versus 93%; OR, 0.31; 95% CI, 0.04–2.1; P = 0.23). This report corroborates studies suggesting that therapeutic doses of primaquine exert no discernible effect on parasitemia by P. falciparum

Short Report: Therapeutic Efficacy of Chloroquine Combined with Primaquine Against \u3ci\u3ePlasmodium falciparum\u3c/i\u3e in Northeastern Papua, Indonesia

Chloroquine combined with primaquine was evaluated for therapy of uncomplicated malaria caused by Plasmodium falciparum in nonimmune Javanese migrants to northeastern Papua, Indonesia. Subjects were randomized to treatment with standard chloroquine therapy (25 mg/kg in 3 doses over the course of 48 hours) with 30 mg primaquine administered daily for 28 days (n = 25) or a placebo of primaquine (n = 28). The 14-day cumulative incidence of therapeutic failure was 56% with primaquine and 79% with placebo (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.1–1.3; P = 0.08). Primaquine administered daily created a marginally significant improvement in therapeutic efficacy at day 14, but not at day 7 (20% versus 36%; OR, 0.2; 95% CI, 0.1–1.8; P = 0.2) or day 28 (82% versus 93%; OR, 0.31; 95% CI, 0.04–2.1; P = 0.23). This report corroborates studies suggesting that therapeutic doses of primaquine exert no discernible effect on parasitemia by P. falciparum

Characteristics of severe anemia and its association with malaria in young children of the Kassena-Nankana District of northern Ghana.

Severe anemia is thought to be the principal underlying cause of malaria death in areas of intense seasonal malaria transmission such as the Kassena-Nankana District of northern Ghana. Factors associated with severe anemia in young children, 6-24 months old, were elucidated by analyzing results of 2 malaria-associated anemia surveys (1996, 2000), separated by 4 years, but conducted in the same community and at the same seasonal time point. Age-adjusted comparison confirmed that the proportion of severely anemic children and overall mean hemoglobin (Hb) levels in the November 2000 sample were significantly improved over those of the 1996 sample (17.5 versus 26.4%, P = 0.03; Hb 7.5 versus 6.9 g/dL, P = 0.002). Weight-for-age Z-scores also indicated a significant improvement in the 2000 sample (-1.93 versus -2.20, P or = 6.0 g/dL, those with severe anemia (Hb < 6.0 g/dL) were older, more frequently parasitemic (odds ratio [OR], 1.60; 95% confidence interval [CI], 1.08-2.35), more often febrile (OR, 2.44; 95% CI, 1.71-3.48), and predominantly male (OR, 1.50; 95% CI, 1.05-2.13). An association was identified in both surveys between severe anemia and residence in the northern part of the district, but no clear link was observed in relation to irrigation. Blood transfusions, a likely surrogate index of severe anemia in young children, followed a distinct seasonal pattern. Evidence suggests that dramatic peaks and troughs of severe anemia are regular and possibly predictable events that may be used to gauge the health and survival of young children in this area

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

Protection of Rhesus Monkeys by a DNA Prime/Poxvirus Boost Malaria Vaccine Depends on Optimal DNA Priming and Inclusion of Blood Stage Antigens

(Pk) malaria. This is a multi-stage vaccine that includes two pre-erythrocytic antigens, PkCSP and PkSSP2(TRAP), and two erythrocytic antigens, PkAMA-1 and PkMSP-1(42kD). The present study reports three further experiments where we investigate the effects of DNA dose, timing, and formulation. We also compare vaccines utilizing only the pre-erythrocytic antigens with the four antigen vaccine.In three experiments, rhesus monkeys were immunized with malaria vaccines using DNA plasmid injections followed by boosting with poxvirus vaccine. A variety of parameters were tested, including formulation of DNA on poly-lactic co-glycolide (PLG) particles, varying the number of DNA injections and the amount of DNA, varying the interval between the last DNA injection to the poxvirus boost from 7 to 21 weeks, and using vaccines with from one to four malaria antigens. Monkeys were challenged with Pk sporozoites given iv 2 to 4 weeks after the poxvirus injection, and parasitemia was measured by daily Giemsa stained blood films. Immune responses in venous blood samples taken after each vaccine injection were measured by ELIspot production of interferon-γ, and by ELISA.1) the number of DNA injections, the formulation of the DNA plasmids, and the interval between the last DNA injection and the poxvirus injection are critical to vaccine efficacy. However, the total dose used for DNA priming is not as important; 2) the blood stage antigens PkAMA-1 and PkMSP-1 were able to protect against high parasitemias as part of a genetic vaccine where antigen folding is not well defined; 3) immunization with PkSSP2 DNA inhibited immune responses to PkCSP DNA even when vaccinations were given into separate legs; and 4) in a counter-intuitive result, higher interferon-γ ELIspot responses to the PkCSP antigen correlated with earlier appearance of parasites in the blood, despite the fact that PkCSP vaccines had a protective effect

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