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Antimalarial drugs have thus far been chiefly derived from two sourcesnatural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products and are underrepresented in typical screening collections. We report the identification of such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase. These molecules are curative in mice at a single, low dose and show activity against all parasite life stages in multiple in vivo efficacy models. Our findings identify bicyclic azetidines with the potential to both cure and prevent transmission of the disease as well as protect at-risk populations with a single oral dose, highlighting the strength of diversity-oriented synthesis in revealing promising therapeutic targets., Author(s): Nobutaka Kato [1]; Eamon Comer [1]; Tomoyo Sakata-Kato [2]; Arvind Sharma [3]; Manmohan Sharma [3]; Micah Maetani [1, 4]; Jessica Bastien [1]; Nicolas M. Brancucci [2]; Joshua A. Bittker [...]

Pregnancy-associated malaria is a leading cause of maternal anemia and low birthweight (1). Measures to prevent pregnancy-associated malaria include insecticide-treated nets, treatment with effective antimalarial drugs, and administration of intermittent [...]

The Affordable Medicines Facility-malaria is an innovative financing mechanism, managed by the Global Fund to Fight AIDS, Tuberculosis and Malaria. This initiative aims to increase the use of artemisinin-based combination therapies for treating malaria. A pilot is underway in eight countries to determine whether the mechanism reduces the consumer price of these drugs and increases their availability in public and private outlets, their market share and their use. To evaluate the pilot, an analysis was done to estimate predetermined 'benchmarks' of success at 1 and 2 years. The analysis used a mixed-methods approach, triangulating data from a literature review with information from 33 interviews with experts. A sensitivity analysis and other methods were used to verify the results. Benchmarks used to determine success include an increase in availability of artemisinin-based combination therapies of40 percentage points from baseline, and an increase in their use of 10-1.5 percentage points from baseline at year 2. These benchmarks were based on evidence that national public health programmes aimed at increasing the use of a specific health commodity in developing countries have generally achieved only modest changes in use within a 2-year time frame. Evaluation should also take individual country contexts into account. Le Fonds pour des medicaments antipaludeens a des prix abordables est un mecanisme de financement innovant, gere par le Fonds mondial de lutte contre le Sida, la tuberculose et la malaria. Cette initiative vise a accroitre l'utilisation des associations therapeutiques a base d'artemisinine dans le traitement du paludisme. Un projet pilote est en cours dans huit pays afin de determiner si ce mecanisme reduit le prix de ces medicaments pour le consommateur et augmente leur disponibilite dans les magasins publics et prives, leur part de marche et leur utilisation. Pour evaluer le projet pilote, une analyse a ete realisee afin d'etablir des criteres predetermines de succes a 1 et 2 ans. L'analyse a eu recours a une approche de methodes mixtes, correlant des donnees issues de la litterature avec les informations recueillies Iors de 33 entretiens avec des experts. Une analyse de sensibilite et d'autres methodes ont ete utilisees pour verifier les resultats. Les criteres utilises pour determiner le succes incluent une augmentation de la disponibilite des traitements a base d'artemisinine de 40 pour cent par rapport au depart et une augmentation de leur utilisation de 10 a 15 pour cent par rapport au depart pour l'annee 2. Ces criteres sont bases sur le constat que les programmes nationaux de sante publique visant a accroitre l'utilisation d'un produit de sante specifique dans les pays en developpement n'ont generalement conduit qu'a de modestes changements des habitudes sur une periode de 2 ans. L'evaluation devrait egalement tenir compte des contextes nationaux specifiques. El Mecanismo de Medicinas Asequibles para la Malaria es un innovador sistema de flnanciacion gestionado por el Fondo Mundial de lucha contra el SIDA, la tuberculosis y la malaria. Esta iniciativa pretende incrementar el uso de las terapias combinadas con artemisinina para el tratamiento de la malaria. Se esta llevando a cabo un estudio preliminar en acho paises para determinar si este mecanismo reduce el precio de dichos farmacos para el consumidor y si incrementa su disponibilidad en distribuidores publicos y privados, su cuota de mercado y su uso. Con el fin de evaluar el estudio preliminar, se llevo a cabo un analisis para estimar unas <> de exito predeterminadas en uno y dos afias. EI analisis empleo un enfoque que combinaba diversos metodos, comparando datas de una revision bibliografica con la informacion obtenida a partir de 33 entrevistas con expertos. Se emplearon tanto un analisis de sensibilidad como otros metodos para verificar los resultados. Las referencias utilizadas para determinar el exito incluyen un aumento de 40 puntos porcentuales en la disponibilidad de las terapias combinadas con artemisinina desde la fecha inicial y un incremento en su uso de entre 10 y 15 puntos porcentuales desde la fecha inicial hasta el segundo ano. Estas referencias se basaron en la evidencia de que, generalmente, los programas sanitarios publicos nacionales que pretendian incrementar el uso de un producto sanitario en paises en desarrollo, solo habian generado cambias moderados en el uso de los mismos durante un plazo de dos anos. La evaluacion tambien deberia tener en cuenta contextos individuales por pais., Introduction The Affordable Medicines Facility-malaria (AMFm) is an innovative financing mechanism that is managed by the Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund). The AMFm aims [...]

Human parvovirus 4 (PARV4), also known as partetravirus, was identified in 2005 from the plasma of an intravenous drug user (IDU) (1). In separate studies that used PCR, PARV4 was [...]

Objective To compare the cost-effectiveness of conventional antimalarial therapy with that of three artemisinin combination treatment regimens in children from Papua New Guinea aged 6 to 60 months. Methods An incremental cost-effectiveness analysis was performed using data from 656 children with Plasmodium falciparum and/or P. vivaxmalaria who participated in a large intervention trial in two clinics in northern Papua New Guinea. The children were randomized to one of the following groups: (i) conventional treatment with chloroquine plus sulfadoxine plus pyrimethamine (CQ+S+P); (ii) artesunate plus S plus P; (iii) dihydroartemisinin plus piperaquine (DHA+PQ); and (iv) artemether plus lumefantrine (A+L). For treatment outcomes, World Health Organization definitions were used. The cost of transport between home and the clinic plus direct health- care costs served as a basis for determining each regimen's incremental cost per incremental treatment success relative to CQ+S+P by day 42 and its cost per life year saved. Findings A+L proved to be the most effective regimen against R falciparum malaria and was highly cost-effective at 6.97 United States dollars (USS) per treatment success (about USS 58 per life year saved). DHA+PQ was the most effective regimen against P. vivax malaria and was more cost-effective than CQ+S+R Conclusion A+L and DHA+PQ are highly cost-effective regimens for the treatment of paediatric P. falciparum and R vivax malaria, respectively, in parts of Papua New Guinea. Future research will be required to determine if these findings hold true for other territories in Asia and Oceania with similar malaria epidemiology. Objectif Comparer le rapport cout -efficacite de la therapie antipaludeenne conventionnelle avec le rapport respectif de trois regimes de traitement associe a base d'artemisinine chez des enfants de Papouasie-NouvelleGuinee ages de 6 a 60 mois. Methodes Une analyse differentielle de cout-efficacite a ete realisee l'aide des donnees de 656 enfants souffrant de Plasmodium falciparum et/ ou de paludisme a P. vivax ayant participe a un vaste essai d'intervention sur le littoral nord-occidental de la Papouasie-Nouvelle-Guinee. Les enfants, qui ont ete presentes dans deux cliniques, ont fait I'objet d'une randomisation vers I'un des regimes therapeutiques suivants : (i) traitement conventionnel avec chloroquine et sulfadoxine-pyrimethamine; (ii) artesunate plus sulfadoxine-pyrimethamine; (iii) dihydroartemisininepiperaquine (DHA+PQ); et (iv) artemether-lumefantrine (A+L). Les resultats des traitements ont ete etablis conformement aux definitions standard de l'Organisation mondiale de la Sante. Le cout du transport entre le domicile et la clinique, ainsi que les frais directs lies aux soins de sante dispenses, ont ete calcules comme base determinante du cout differentiel de chaque regime par traitement reussi au jour 42, et son cout par annee de vie sauvee. Resultats A+L s'est revele comme le regime le plus efficace du point de vue clinique dans le traitement du paludisme a P. falciparum et representait un excellent rapport cout-efficacite a 6,97 dollars par traitement reussi (environ 58 dollars par annee de vie sauvee). DHA+PQ representait l'association de traitement la plus efficace dans la lutte contre le paludisme a P. vivax, et etait d'un meilleur rapport cout-efficacite que le traitement conventionnel contre le paludisme. Conclusion A+L et DHA+PQ sont des regimes tres rentables pour traiter, respectivement, le paludisme pediatrique a P. falciparum et a P vivax, dans les regions de la Papouasie-Nouvelle-Guinee. Des recherches futures seront necessaires arin de determiner si ces resultats se confirment dans d'autres territoires d'Asie et d'Oceanie presentant une epidemiologie de paludisme similaire. Objetivo Comparar la rentabilidad del tratamiento antipaludico convencional respecto a la de los tres tratamientos combinados con artemisinina en ninos de entre 6 y 60 meses de Papua Nueva Guinea. Metodos Se realizo un analisis incremental de la rentabilidad con los datos procedentes de 656 ninos con malaria por Plasmodium falciparum y/o por R vivax que participaron en un ensayo intervencionista a gran escala en la costa Norte de Papua Nueva Guinea. A los ninos que acudieron a dos consultorios, se les asigno aleatoriamente uno de los siguientes tratamientos: (a) tratamiento tradicional con cloroquina, sulfadoxina y pirimetamina; (b) artesunato, sulfadoxina y pirimetamina; (c) dihidroartemisinina y piperaquina (DHA+PQ); y (d) artemeter y lumefantrina (A+L). Se definieron los resultados terapeuticos siguiendo las definiciones normalizadas de la Organizacion Mundial de la Salud. Como base para la determinacion de los costes incrementales por cada logro terapeutico alcanzado a los 42 dias y su coste por ano de vida salvado, se calculo el coste del transporte entre el hogar y el centro de salud, junto con los gastos directos ocasionados por la asistencia sanitaria proporcionada. Resultados Desde el punto de vista clinico, el tratamiento mas eficaz contra la malaria por R falciparum fue el A+L, con una rentabilidad muy elevada de 6,97 dolares norteamericanos (USS) por logro terapeutico (unos 58 USS por ano de vida salvado). La combinacion terapeutica mas eficaz contra la malaria producida por R vivaxfue la DHA+PQ y resulto ser mas rentable que el tratamiento antipaludico habitual. Conclusion En algunas zonas de Papua Nueva Guinea, les tratamientos A+L y DHA+PQ resultan muy rentables en el tratamiento pediatrico contra la malaria por R falciparum y R vivax, respectivamente. Es preciso que se investigue mas en profundidad para determinar si estos resultados tambien son validos para otras regiones de Asia y Oceania que presenten una epidemiologia de malaria similar., Introduction Recent estimates show that Plasmodium falciparum causes 225 to 500 million cases of malaria and nearly one million malaria-related deaths worldwide each year. (1-3) Of these deaths, 96% take [...]

Although gastrointestinal stromal tumors (GISTs) harboring activating KIT or platelet-derived growth factor receptor A (PDGFRA) mutations respond to treatment with targeted KIT/PDGFRA inhibitors such as imatinib mesylate, these treatments are rarely curative. Most often, a sizeable tumor cell subpopulation survives and remains quiescent for years, eventually resulting in acquired resistance and treatment failure. Here, we report that imatinib induces autophagy as a survival pathway in quiescent GIST cells. Inhibiting autophagy, using RNAi-mediated silencing of autophagy regulators (ATGs) or antimalarial lysosomotrophic agents, promotes the death of GIST cells both in vitro and in vivo. Thus, combining imatinib with autophagy inhibition represents a potentially valuable strategy to promote GIST cytotoxicity and to diminish both cellular quiescence and acquired resistance in GIST patients. imatinib | targeted therapy | quiescence doi/ 10.1073/pnas.1000248107

A study was conducted to ascertain the efficacy of artemisinin -based combination therapies as a main treatment for Plasmodium falciparum malaria following reports of declined efficacy of this drug along the Thai-Cambodian border. Results revealed that P. falciparum manifests reduced susceptibility in vivo to artesunate in western Cambodia compared to northwestern Thailand and urgent measures should be taken to address the problem.

Problem statement: Antimalaria drugs are highly consumed in Africa due to increase prevalent of malaria attacks. Though the disease is often cured with some antimalarials the physiologic effects of such drugs may not be considered in pharmacologic preparations and in prescriptions. Such non consideration is likely to result in serious health problems which may outweigh the effects of malaria disease or become double jeopardy in the event of management of the disease. Objective;. To determine the negative effects of amalar, chloroquine, cotecxin and fansidar on bilirubin concentration. Approach: Thirty male and female albino rats weighing 80-141 g were used for the study. The animals were grouped into four drugs with six animals in each drug group including control. The drugs (powdered) were administered orally per weights of the animals and based on the curative and preventive dosages using canula by-passing the esophagus and delivered into the stomach. The effect of the antimalaria drugs was monitored for 28 days by colorimetric measurement of bilirubin concentration in the blood plasma collected by cardiac punture. Results: Fansidar decreased the concentration of bilirubin significantly as compared with that of control (8.64[+ or -]0.33), control, 16.65[+ or -]1.00) p0.05). Conclusion: The study had unveiled the possibility of erythropoietic porphyria, ineffective haemoglobination and anaemia in the administration of amalar, chloroquine, and fansidar and the need to encourage potent and cells friendly malaria therapies to avoid cellular damages. Key words: Bilirubinaemia, physiologic index, antimalarials, INTRODUCTION Bilirubin is a major end product of haemoglobin degradation. It is formed from the conversion of porphyrin component of haemoglobin by macrophages and kupffer cells when the erythrocytes have [...]

A research conducted to find the pharmacokinetics, efficiency and safety of rectally administered artesunate, artemisinin, dihydroartemisinin and artemether for the treatmet of malaria is presented.

The ability to treat and control Plasmodium falciparum infection through chemotherapy has been compromised by the advent and spread of resistance to antimalarial drugs. Research in this area has identified the P. falciparum chloroquine resistance transporter (PfCRT) and the multidrug resistance-1 (PfMDR1) transporter as key determinants of decreased in vitro susceptibility to several principal antimalarial drugs. Transfection-based in vitro studies are consistent with clinical findings of an association between mutations in the pfcrt gene and failure of chloroquine treatment, and between amplification of the pfmdr1 gene and failure of mefloquine treatment. Many countries are now switching to artemisinin-based combination therapies. These incorporate partner drugs of which some have an in vitro efficacy that can be modulated by changes in pfcrt or pfmdrl. Here, we summarize investigations of these and other recently identified P. falciparum transporters in the context of antimalarial mode of action and mechanisms of resistance.

Mefloquine is the preferred drug to prevent malaria in those traveling to countries with the disease. Malaria is a parasitic infection spread by mosquitoes that affects up to 30,000 North American and European travelers each year. Parasitic resistance to chloroquine, a drug used since the 1940's, has developed in most endemic areas in Africa, Asia and South America. Resistance to mefloquine in Southeast Asia has raised concern about the long-term utility of this drug. Insect repellants and screens reduce contact with mosquitoes and are important means of preventing malaria., Individuals from industrialized nations frequently travel to countries with malaria, so health care providers need to be familiar with current recommendations for prevention of malaria. Changes in drug susceptibility of malaria parasites and evolving knowledge of how well drugs are tolerated necessitate periodic review of guidelines for prophylaxis of malaria, especially of chloroquine-resistant Plasmodium falciparum malaria. Mefloquine is the drug of choice for chemoprophylaxis for most travelers, with doxycycline and chloroquine being less effective alternatives. Mefloquine is well tolerated at prophylactic dosages, but anecdotal reports have raised concerns about its adverse effects. Resistance to this drug has emerged in parts of Southeast Asia and may spread to other regions of the world. The major disadvantages of doxycycline are the need for daily dosing, its contraindication for young children and pregnant women, and its adverse effects. Chloroquine is effective for prophylaxis only in Central America, the Caribbean, and parts of the Middle East. Few new drugs will be available in the near future because of reduced funding for antimalarial drug research and development; therefore, the usefulness of currently available drugs needs to be prolonged by rational use. Increased efforts should be made to ensure that alternative drugs will be available for prevention of malaria. JAMA 1997;278:1767-1771

Clinicians need to become more aware of the risks and benefits of prophylactic treatments for malaria as travel increases to regions where malaria is present. Malaria is spread by infected mosquitoes. Chloroquine has long been used for prevention, but there are now strains of malaria-causing parasites that are resistant to chloroquine. Infection with strains of Plasmodium (P.) falciparum that are chloroquine-resistant can cause death in severe cases. P. ovale, P. vivax and P. malariae can cause milder bouts of malaria. Malaria can be prevented by minimizing exposure to mosquitoes or by eradicating the organism from the blood. Relapse can be prevented by destroying the latent organism present in the liver. The most commonly used drugs include chloroquine, primaquine, mefloquine, doxycycline and chloroguanide hydrochloride.

Hydroxychloroquine is an antimalarial drug which, like other antimalarials such as chloroquine and quinacrine, is thought to relieve some of the symptoms of systemic lupus erythematosus. Hydroxychloroquine is thought by many to control the skin and mucous membrane lesions, the arthritis and pleuritic pain, and the malaise and easy fatigability of patients with lupus erythematosus. However, this belief is not firmly supported by experimental evidence. There is also some concern that, although such drugs are clearly safe in the treatment of malaria, the long-term consequences of their chronic use in the treatment of lupus erythematosus is less certain. To determine if the use of hydroxychloroquine is indeed justified on the basis of its benefit to the patient, a study was organized of 47 women with stable lupus who had been taking hydroxychloroquine for an average of three years. Twenty-five patients were randomly selected to continue to receive hydroxychloroquine, while 22 were randomly selected to begin receiving placebo for 24 weeks. Neither the patients nor their physicians knew which treatment they were receiving. It was observed that during the test period, 16 of 22 patients receiving placebo had flare-ups of their lupus, in contrast to 9 of 25 continuing with hydroxychloroquine. The risk of a flare-up was 2.5 times higher in the placebo group, and risk of a severe flare-up was over six times greater in the placebo group than the hydroxychloroquine group. The results indicate that patients taking hydroxychloroquine are more likely to have a flare-up if they discontinue the drug; the results also support the clinical supposition that hydroxychloroquine is useful in the treatment of lupus erythematosus. (Consumer Summary produced by Reliance Medical Information, Inc.)

Malaria chemoprophylaxis was originally primarily dependent on the use of chloroquine. However, since the development of chloroquine resistance in Plasmodium falciparum, other new and more powerful drugs have been introduced for malaria prevention and treatment. Unfortunately, with the use of the newer drugs, serious adverse reactions have been reported, ranging from transient nausea and vomiting to more serious outcomes, including death. Five problems prevented the determination of risk of adverse reactions to these malaria drugs: lack of awareness of early alerts; inadequate use of national registers; poor attention to epidemiological data; inadequate verification; and inadequate records. Adverse reactions may be classified as dose-dependent, dose-independent and pseudo-allergic. Most of the adverse reactions to these drugs were dose-dependent and may have been related to: changes in drug formulation, route of administration, noncompliant usage, individual genetic variance, patient age, pregnancy, drug interactions, and concomitant illness. The detection of adverse drug reactions involves a phased, monitored study examining pharmacokinetics and pharmacologic properties, therapeutic effectiveness, dose determination, safety and efficacy evaluation, and a final long-term postmarketing evaluation. Some of the more serious reactions have occurred following the use of pyrimethamine-sulphadoxine, pyrimethamine-dapsone, and amodiaquine. Specific methodology for assessing the risk of adverse drug reactions are described, and recommendations are made for developing a more comprehensive system of risk assessment. These include specific details and steps to be followed during prelicensing management of new drugs or higher doses, and specific procedures for licensing and post-licensing management, such as reviews of national registers and monitoring high-risk groups. (Consumer Summary produced by Reliance Medical Information, Inc.), Ascertainment of risk of serious adverse reactions associated with chemoprophylactic antimalarial drugs Introduction Because of chloroquine-resistance in Plasmodium falciparum, other potentially more toxic drugs were introduced for the prevention and [...]

Background: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs). Methods and Findings: A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p = 0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p = 0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p = 0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p = 0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p = 0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis. Conclusions: An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs. Trial registration: ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary., Introduction Many African pregnant women are infected with HIV, and many of them are also exposed to falciparum malaria [1,2]. It is estimated that at least 1 million pregnancies per [...]

Despite research on a promising drug isolated from a traditional Chinese remedy for malaria, the search should continue for effective antimalarial drugs. Artemisinin and its derivatives artesunate and artemether are derived from the Chinese herbal medicine qinghaosu. Two 1996 studies documented that artemether is as effective as quinine in treating malaria. However, death rates were still 13% to 21% using artemether compared to 17% to 22% using quinine. And artemether may have serious neurological side effects.

Byline: Mahesh. Belhekar, Manjari. Advani, Sudhir. Pawar Objectives: Antimalarial drugs are commonly prescribed for the treatment of malaria and suspected cases of malaria in India. The recent trend is to [...]

Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or 'attack' phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission., Introduction Antimalarial drugs are used to treat malaria illness, to prevent both infection and disease caused by Plasmodia, to eliminate dormant malaria parasites from the liver, and to prevent malaria [...]

Various protein constructs of a parasitic arginase from Plasmodium falciparum were explored to identify an optimally active enzyme form for inhibition and structural studies and to probe the structure and function of two polypeptide insertions unique to malarial arginase. The results suggested that inhibition of malarial arginase might serve as a possible candidate for antimalarial therapy against liver-stage infection, and amino-6-boronohexanoic acid (ABH) might serve as a lead for the development of inhibitors.

Lupus erythematosus is a variable clinical entity, and its treatment is largely empirical. Many treatments enthusiastically endorsed in the past have proven to be of little benefit. Severe symptoms or acute outbreaks may demand drug therapy with prednisone or even cyclophosphamide. For some time, however, there has been a suggestion that antimalarial drugs may provide some benefit for patients with mild systemic symptoms and rash despite the fact that there was little clinical data on which to base this belief. Now, however, an article published in the January 17, 1991 issue of The New England Journal of Medicine does provide some data which shed more light on this question. The researchers studied a group of women who had been taking hydroxychloroquine; these women were randomly assigned to either continue with the drug or switch to placebo. Neither the patients nor the physicians knew which patients were getting which treatment. They found that the patients who were removed from the drug experienced significantly more flare-ups of their disease than did the women who continued hydroxychloroquine treatment. While this evidence indicates that hydroxychloroquine should play a role in the treatment of mild systemic lupus, the results do not provide new indications for the use of this drug. The usefulness of the drug in serious or acute disease remains unknown, nor is it known how well other patient groups will respond which were not represented by the Canadian study. Nevertheless, the results of the study indicate that further research on the usefulness of hydroxychloroquine in the treatment of systemic lupus erythematosus should be encouraged. (Consumer Summary produced by Reliance Medical Information, Inc.)

The study attempts to investigate the most effective antimalarial therapies in children from Papua New Guinea. The results indicate that artemether-lumefantrine was the most effective regimen as compared to the others.