We evaluated the efficacy and safety of halofantrine in 19 patients with acute uncomplicated falciparum malaria. Each patient received oral halofantrine hydrochloride 500 mg every 6 hours for 3 doses (total 1.5 g). In almost all the patients clinical symptoms of malaria and parasitaemia disappeared within 2 and 3 days, respectively, of starting treatment. We observed no recurrence of parasitaemia during 14 days of follow-up. Tolerance to halofantrine was good except for minor and self-limiting gastrointestinal side-effects. Haematological and biochemical indices were not seriously affected. Halofantrine-induced prolongation of Q-T/Q-Tc intervals was the consistent cardiac manifestation in 84% of patients. The Q-T/Q-Tc interval prolongation increased with each dose; it reached a maximum between 18 and 24 hours and thereafter returned to baseline. These preliminary data indicate that, apart from the cardiac side-effects, halofantrine is an effective and safe drug, well tolerated by most of the patients in the study. PIP: The authors evaluated the efficacy and safety of halofantrine in 19 patients with acute uncomplicated falciparum malaria. Each patient received oral halofantrine hydrochloride 500 mg every 6 hours, for a total of 3 doses (total 1.5 g). In almost all the patients clinical symptoms of malaria and parasitemia disappeared within 2 and 3 days, respectively, of starting treatment. They observed no recurrence of parasitemia during 14 days of follow-up. Tolerance to halofantrine was good except for minor and self-limiting gastrointestinal side effects. Hematological and biochemical indices were not seriously affected. Halofantrine-induced prolongation of Q-T/Q-Tc intervals was the consistent cardiac manifestation in 84% of patients. The Q-T/Q-Tc interval prolongation increased with each dose; it reached a maximum between 18 and 24 hours and thereafter returned to baseline. These preliminary data indicate that, apart from the cardiac side effects, halofantrine is an effective and safe drug, well tolerated by most of the patients in the study.
Antimalarials - administration & ; dosage ; Antimalarials - therapeutic use ; Electrocardiography ; Malaria, Falciparum - blood

In Vanuatu malaria is a major killer, especially of young children. As most deaths occur outside the hospital it is very important to have simple, clear guidelines on the management of patients with suspected malaria for the primary health care workers who treat the majority of cases. Despite the encouragement of early treatment, malaria was the major cause of death in children after the neonatal period in 1988. During 1989 and 1990 the treatment of malaria in Vanuatu was reviewed with the aim of trying to reduce the morbidity and mortality from the disease. New guidelines were included in the Vanuatu Health Workers' Manual, issued to all nurses, nurse practitioners and doctors in 1991. The major changes were the introduction of immediate slide microscopy, the use of a combination of chloroquine and sulphadoxine-pyrimethamine for Plasmodium falciparum malaria and for children under 5 years and pregnant women, the discontinuation of single-dose primaquine (previously given as a gametocytocidal agent), and the use of a loading dose of quinine. The constraints of the previous guidelines, the rationale for the changes and the expected improvements resulting from using the new treatments are discussed.
Adolescent ; Adult ; Antimalarials - administration & ; dosage ; Child, Preschool ; Chloroquine - administration & ; dosage ; Practice Guidelines as Topic

OBJECTIVEPhytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fibre of Dwarf Red variety of Cocos nucifera were evaluated in this study.

METHODSThe dried powdered husk fibre was exhaustively extracted with hexane, ethyl acetate and methanol successively and the methanolic extract was screened for flavonoids, phenolics, tannins, alkaloids, steroids, triterpenes, phlobatannins, anthraquinones and glycosides. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei NK65-infected mice, to which the extract was administered at doses of 31.25, 62.5, 125, 250 and 500 mg/kg body weight (BW). Toxicity of the extract was evaluated in rats using selected hematological parameters and organ function indices after orally administering doses of 25, 50 and 100 mg/kg BW for 14 d.

RESULTSPhytochemical analysis revealed the presence of alkaloids, tannins, phenolics, saponins, glycosides, steroids and anthraquinones in the extract. Moreover, the extract reduced parasitemia by 39.2% and 45.8% at doses of 250 and 500 mg/kg BW respectively on day 8 post-inoculation. Various hematological parameters evaluated were not significantly altered (P>0.05) at all doses of the extract, except red blood cell count which was significantly elevated (P<0.05) at 100 mg/kg BW. The extract significantly increased (P<0.05) urea, creatinine, cholesterol, high-density lipoprotein-cholesterol and bilirubin concentrations in the serum as well as atherogenic index, while it reduced albumin concentration significantly (P<0.05) at higher doses compared to the controls. Alanine aminotransferase activity was reduced in the liver and heart significantly (P<0.05) but was increased in the serum significantly (P<0.05) at higher doses of the extract compared to the controls.

CONCLUSIONThe results suggest that methanolic extract of the Dwarf red variety has partial antimalarial activity at higher doses, but is capable of impairing normal kidney and liver function as well as predisposing subjects to cardiovascular diseases.

Animals ; Antimalarials ; administration & dosage ; adverse effects ; pharmacology ; Cocos ; Dose-Response Relationship, Drug ; Malaria ; drug therapy ; Mice ; Plant Extracts ; administration & dosage ; adverse effects ; pharmacology ; Plasmodium berghei ; Rats ; Rats, Wistar

OBJECTIVEThe study aimed to evaluate and compare the efficacy and safety of dihydroartemisinin-piperaquine phosphate (Artekin) and artemisinin-piperaquine (Artequick) in the treatment of uncomplicated falciparum malaria.

METHODSA total of 103 uncomplicated falciparum malaria patients were enrolled and randomly assigned to two groups: 52 cases in the Artequick group, and 51 cases in the Artekin group. The patients in the Artequick group were administered with Artequick, twice in 24 h, whereas the patients in the Artekin group were given Artekin 4 times in 2 days. The mean parasite clearance time, mean fever clearance time, 28-day cure rate and parasite recrudescence rates of the two groups were then compared.

RESULTSThe mean parasite clearance time and the mean fever clearance time were 43.2+/-13.9 h and 24.7+/-9.9 h, in the Artequick group, and 36.5+/-17.1 h and 22.7+/-11.2 h, in the Artekin group. In both groups the 28-day cure rate was 100%, and the parasite recrudescence rate was 0.

CONCLUSIONBoth medicines had high cure rates, low recrudescence rates, and no serious adverse reactions. The administration of Artequick, however, was more convenient and lower incidence of gastrointestinal side effects than that of Artekin, so as to increase the efficacy in the malaria population.

Adolescent ; Adult ; Anti-Infective Agents ; administration & dosage ; adverse effects ; Antimalarials ; administration & dosage ; Artemisinins ; administration & dosage ; adverse effects ; Drug Combinations ; Female ; Humans ; Integrative Medicine ; Malaria, Falciparum ; drug therapy ; Male ; Quinolines ; administration & dosage ; adverse effects ; Treatment Outcome ; Young Adult

OBJECTIVETo determine the main factors which affect the percutaneous penetration of artesunate and provide efficient data for the artesunate transdermal delivery system.

METHODTransdermal speed constant and accumulative amount of 12 hours were used for the estimations of various reservior vehicles, and the supplement orthodox design was used to study the effect of pH, various proportion of IPA/Water/IPM, and drug concentration.

RESULTDrug concentration and pH were the main factors which affected the percutaneous penetration of artesunate.

CONCLUSIONThe suitable reservior vehicle can prompt the percutaneous penetration of artesunate, and artesunate TTS will be made with further studies.

2-Propanol ; pharmacology ; Administration, Cutaneous ; Animals ; Antimalarials ; administration & dosage ; pharmacokinetics ; Artemisinins ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Hydrogen-Ion Concentration ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Sesquiterpenes ; administration & dosage ; pharmacokinetics ; Skin Absorption ; drug effects

The annual incidence of Plasmodium vivax malaria that reemerged in the Republic of Korea (ROK) in 1993 increased annually, reaching 4,142 cases in 2000, decreased to 864 cases in 2004, and once again increased to reach more than 2,000 cases by 2007. Early after reemergence, more than two-thirds of the total annual cases were reported among military personnel. However, subsequently, the proportion of civilian cases increased consistently, reaching over 60% in 2006. P. vivax malaria has mainly occurred in the areas adjacent to the Demilitarized Zone, which strongly suggests that malaria situation in ROK has been directly influenced by infected mosquitoes originating from the Democratic People's Republic of Korea (DPRK). Besides the direct influence from DPRK, local transmission within ROK was also likely. P. vivax malaria in ROK exhibited a typical unstable pattern with a unimodal peak from June through September. Chemoprophylaxis with hydroxychloroquine (HCQ) and primaquine, which was expanded from approximately 16,000 soldiers in 1997 to 200,000 soldiers in 2005, contributed to the reduction in number of cases among military personnel. However, the efficacy of the mass chemoprophylaxis has been hampered by poor compliance. Since 2000, many prophylactic failure cases due to resistance to the HCQ prophylactic regimen have been reported and 2 cases of chloroquine (CQ)-resistant P. vivax were reported, representing the first-known cases of CQ-resistant P. vivax from a temperate region of Asia. Continuous surveillance and monitoring are warranted to prevent further expansion of CQ-resistant P. vivax in ROK.
Antimalarials/administration & dosage ; Chemoprevention ; *Disease Outbreaks ; Drug Resistance ; Humans ; Malaria, Vivax/drug therapy/*epidemiology/parasitology/prevention & control ; Military Personnel ; Plasmodium vivax/drug effects/*physiology ; Republic of Korea/epidemiology

The purpose of treatment for uncomplicated malaria is to produce a radical cure using the combination of: artesunate (4 mg/kg/day) plus mefloquine (8 mg/kg day) for 3 days; a fixed dose of artemether and lumefantrine (20/120 mg tablet) named Coartem (4 tablets twice a day for three days for adults weighing more than 35 kg); quinine 10 mg/kg 8-hourly plus tetracycline 250 mg 6-hourly for 7 days (or doxycycline 200 mg as an alternative to tetracycline once a day for 7 days) in patients aged 8 years and over; Malarone (in adult 4 tablets daily for 3 days). In treating severe malaria, early diagnosis and treatment with a potent antimalarial drug is recommended to save the patients life. The antimalarial drugs of choice are: intravenous quinine or a parenteral form of an artemisinin derivative (artesunate i.v./i.m. for 2.4 mg/kg followed by 1.2 mg/kg injection at 12 and 24 hr and then daily for 5 days; artemether i.m. 3.2 mg/kg injection followed by 1.6 mg/kg at 12 and 24 hrs and then daily for 5 days; arteether i.m. (Artemotil) with the same dose of artemether or artesunate suppository (5 mg/kg) given rectally 12 hourly for 3 days). Oral artemisinin derivatives (artesunate, artemether, and dihydroartemisinin with 4 mg/kg/day) could replace parenteral forms when patients can tolerate oral medication. Oral mefloquine (25 mg/kg divided into two doses 8 hrs apart) should be given at the end of the artemisinin treatment course to reduce recrudescence.
Adult ; Antimalarials/*administration & dosage ; Child ; Clinical Trials as Topic ; Drug Administration Routes ; Drug Administration Schedule ; Drug Therapy, Combination ; Humans ; Malaria/*drug therapy ; Recurrence/prevention & control ; Severity of Illness Index ; Thailand ; Time Factors

The anti-malarial potential of different parts of Allophylus africanus P. Beauv and Tragia benthamii Baker were determined in vivo for suppressive, curative and cytotoxic activities in mice receiving 0.2 mL of a standard inoculum size of 1 × 10(7) infected erythrocytes of Plasmodium berghei (NK-65) intraperitoneally. The A. africanus extracts suppressed parasitaemia following administration to infected mice by 92.82%-97.81% on day 7 post-infection against 96.81% for chloroquine. The infected extract-treated animals had significantly moderate (P < 0.05) packed cell volume (PCV) compared with the infected, untreated animals. Phytochemical screening revealed a predominance of tannins, saponins, flavonoids and carbohydrates in all parts of A. africanus, and alkaloids instead of flavonoids in the extract of T. benthamii. The results suggest that the extract possesses considerable antimalarial activity. These results support further studies on A. africanus.
Animals ; Antimalarials ; administration & dosage ; chemistry ; Drug Evaluation, Preclinical ; Euphorbiaceae ; chemistry ; Female ; Humans ; Malaria ; drug therapy ; parasitology ; Male ; Mice ; Plant Extracts ; administration & dosage ; chemistry ; Plasmodium berghei ; drug effects ; Sapindaceae ; chemistry

Changing patterns of the reemerging Plasmodium vivax malaria in the Republic of Korea (South Korea) during the period 1993 to 2005 are briefly analyzed with emphasis on the control measures used and the effects of meteorological and entomological factors. Data were obtained from the Communicable Diseases Monthly Reports published by the Korea Center for Disease Control and Prevention, and webpages of World Health Organization and United Nations. Meteorological data of Kangwon-do (Province) were obtained from local weather stations. After its first reemergence in 1993, the prevalence of malaria increased exponentially, peaking in 2000, and then decreased. In total, 21,419 cases were reported between 1993 and 2005 in South Korea. In North Korea, a total of 916,225 cases were reported between 1999 and 2004. The occurrence of malaria in high risk areas of South Korea was significantly (P<0.05) correlated with the mosquito population but not with temperature and rainfall. Control programs, including early case detection and treatment, mass chemoprophylaxis of soldiers, and international financial aids to North Korea for malaria control have been instituted. The situation of the reemerging vivax malaria in the Republic of Korea is remarkably improving during the recent years, at least in part, due to the control activities undertaken in South and North Korea.
Seasons ; Plasmodium vivax/drug effects ; Military Personnel/statistics & numerical data ; Malaria, Vivax/*epidemiology/parasitology/*prevention & control ; Korea/epidemiology ; Incidence ; Humans ; Disease Outbreaks/*prevention & control ; Communicable Diseases, Emerging/*epidemiology/parasitology/*prevention & control ; Chloroquine/administration & dosage ; Antimalarials/administration & dosage ; Anopheles/parasitology ; Animals

Complicated malaria is mainly caused by Plasmodium falciparum, but, increasingly, Plasmodium vivax is also being reported as a cause. Since the reemergence of indigenous vivax malaria in 1993, cases of severe malaria have been steadily reported in Korea. Herein, we report a case of vivax malaria complicated by adult respiratory distress syndrome (ARDS) that was successfully managed with extracorporeal membrane oxygenation (ECMO). A 59-year-old man presented at our hospital with fever and abdominal pain, which had persisted for 10 days. On admission, the patient had impaired consciousness, shock, hypoxia and haziness in both lungs, jaundice, thrombocytopenia and disseminated intravascular coagulation, metabolic acidosis, and acute kidney injury. A peripheral blood smear and a rapid diagnostic test verified P. vivax mono-infection. Ten hours after admission, hypoxia became more severe, despite providing maximal ventilatory support. The administration of antimalarial agents, ECMO, and continuous venovenous hemofiltration resulted in an improvement of his vital signs and laboratory findings. He was discharged from the hospital 7 weeks later, without any sequelae.
Acute Kidney Injury ; Anoxia ; Antimalarials/*administration & dosage ; Extracorporeal Membrane Oxygenation ; Humans ; Lung/radiography ; Malaria, Vivax/*complications/diagnosis/radiography/therapy ; Male ; Middle Aged ; Multiple Organ Failure ; Plasmodium vivax/*isolation & purification ; Republic of Korea ; Respiratory Distress Syndrome, Adult/*complications/radiography/therapy ; Treatment Outcome