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Objective To determine household and health-care provider costs associated with Plasmodium vivax infection across a range of endemic settings. Methods We collected cost data alongside three multicentre clinical trials of P vivax treatment in Afghanistan, Brazil, Colombia, Ethiopia, Indonesia, Philippines, Peru, Thailand and Viet Nam conducted between April 2014 to December 2017. We derived household costs from trial participant surveys administered at enrolment and again 2 weeks later to determine the costs of treatment and transportation, and the number of days that patients and their household caregivers were unable to undertake their usual activities. We determined costs of routine care by health-care providers by micro-costing the resources used to diagnose and treat P vivax at the study sites. Findings The mean total household costs ranged from 8.7 United States dollars (US$; standard deviation, SD: 4.3) in Afghanistan to US$ 254.7 (SD: 148.4) in Colombia. Across all countries, productivity losses were the largest household cost component, resulting in mean indirect costs ranging from US$ 5.3 (SD: 3.0) to US$ 220.8 (SD: 158.40). The range of health-care provider costs for routine care was US$ 3.6-6.6. The cost of administering a glucose-6-phosphate-dehydrogenase rapid diagnostic test, ranged from US$ 0.9 to 13.5, consistently lower than the costs of the widely-used fluorescent spot test (US$ 6.3 to 17.4). Conclusion An episode of P vivax malaria results in high costs to households. The costs of diagnosing and treating P vivax are important inputs for future cost-effectiveness analyses to ensure optimal allocation of resources for malaria elimination. Objectif Determiner les couts, pour les menages et les prestataires de soins, associes a l'infection par Plasmodium vivax dans differentes zones endemiques. Methodes Nous avons recueilli des donnees sur les couts a l'occasion de trois essais cliniques multicentres relatifs au traitement contre P vivax menes en Afghanistan, au Bresil, en Colombie, en Ethiopie, en Indonesie, aux Philippines, au Perou, en Thailande et au Viet Nam entre avril 2014 et decembre 2017. Nous avons calcule les couts pour les menages a partir d'enquetes realisees aupres des participants aux essais, lors de leur admission puis 2 semaines plus tard, afin de determiner les couts de traitement et de transport ainsi que le nombre de jours ou les patients et leurs aidants familiaux n'avaient pu accomplir leurs activites habituelles. Nous avons determine le cout des soins courants par les prestataires de soins en calculant le cout individuel des ressources utilisees pour diagnostiquer et traiter P vivax sur le site des etudes. Resultats Les couts totaux moyens pour les menages allaient de 8.7 dollars des Etats-Unis ($ US; ecart type, ET: 4,3) en Afghanistan a 254.7 $ US (ET: 148,4) en Colombie. Tous pays confondus, les pertes de productivity etaient la principale composante des couts pour les menages, puisqu'elles entrainaient des couts indirects moyens allant de 5,3 $ US (ET: 3,0) a 220,8 $ US (ET: 158,40). En ce qui concerne les prestataires de soins, le cout des soins courants allait de 3,6 a 6,6 $ US. Le cout de realisation d'un test de diagnostic rapide base sur le glucose6- phosphate-deshydrogenase variait de 0,9 $ US a 13,5 $ US, un cout toujours inferieur a celui du tres repandu test par fluorescence (6,3 $ US a 17,4 $ US). Conclusion Un episode de paludisme a P vivax entraine des couts eleves pour les menages. Connaitre les couts du diagnostic et du traitement de P vivax sera fort utile aux futures analyses cout-efficacite. Cela permettra d'affecter les ressources de maniere optimale en vue d'eradiquer le paludisme. Objetivo Determinar los costos del hogar y de los proveedores de atencion de la salud asociados con la infeccion por Plasmodium vivax en una variedad de ambitos endemicos. Metodos Se recopilaron datos de costos junto con tres ensayos clinicos multicentricos del tratamiento con P. vivax en Afganistan, Brasil, Colombia, Etiopia, Filipinas, Indonesia, Peru, Tailandia y Vietnam realizados entre abril de 2014 y diciembre de 2017. Los costos del hogar se derivaron de las encuestas de los participantes del ensayo administradas en el momento de la inscripcion y de nuevo dos semanas despues para determinar los costos del tratamiento y del transporte, asi como el numero de dias en que los pacientes y los cuidadores en el hogar no pudieron llevar a cabo sus actividades habituales. Se determinaron los costos de la atencion de rutina por parte de los proveedores de atencion de la salud mediante el microcosto de los recursos utilizados para diagnosticar y tratar el P. vivax en los centros de estudio. Resultados Los costos totales promedio de los hogares oscilaron entre 8,7 dolares estadounidenses (USD; desviacion estandar, DE: 4,3) en Afganistan y 254,7 USD (DE: 148,4) en Colombia. En todos los paises, las perdidas de productividad fueron el mayor componente del costo del hogar, lo que dio lugar a costos indirectos promedios que oscilaron entre 5,3 y 220,8 USD. El rango de los costos de los proveedores de atencion de la salud para la atencion de rutina fue de 3,6 a 6,6 USD. El costo por administrar una prueba de diagnostico rapido de la glucosa-6- fosfatodeshidrogenasa, vario de 0,9 a 13,5 USD, consistentemente mas bajo que los costos de la prueba de fluorescencia aleatoria ampliamente utilizada (6,3 a 17,4 USD). Conclusion Un episodio de malaria por P. vivax tiene como resultado un alto costo para el hogar. Los costos del diagnostico y tratamiento de P. vivax son insumos importantes para futuros analisis de costoefectividad que aseguren una asignacion optima de recursos para la eliminacion de la malaria., Introduction Outside Sub-Saharan Africa, Plasmodium vivax is now the predominant cause of malaria, affecting 14.0 million patients in 2016. (1) While cost-effectiveness analyses can inform the efficient provision of health-care [...]

Case Descriptions Patient 1. A 48-year-old male construction worker, with no preceding medical illnesses, was admitted to the intensive care unit of a hospital in Hanoi. For a few days [...]

Objective To test a novel methodology to define age-based dosing regimens for the treatment of malaria with a new, user-friendly, blister-packaged fixed-dose combination of artesunate and amodiaquine. Methods A weight-for-age reference database of 88 054 individuals from sub-Saharan Africa was compiled using data from Demographic Health Surveys, observational and intervention studies, and standardized for sex, age and malaria risk. We then determined the optimal tablet strength (milligram (mg) per tablet) and age-dose categories for the combination of artesunate and amodiaquine. The proportions of patients predicted to receive doses within newly defined therapeutic ranges for amodiaquine (7-15 mg/kg/day) and artesunate (2-10 mg/kg/day), were estimated for different age categories and mg tablet strengths using models based on the weight-for-age reference database. Findings The optimal paediatric (p) and adult (a) strength tablets contained 25/67.5 and 100/270 mg Artesunate/amodiaquine, respectively. A regimen with five age categories: 0-1 months (1/2 p), 2-11 months (1 p), 1-5 years (2 p), 6-13 years (1 a), and [greater than or equal to] 14 years (2 a) had an overall dosing accuracy of 83.4% and 99.9% for amodiaquine and artesunate, respectively. Conclusion The proposed method to use weight-for-age reference data from countries where malaria is endemic is a useful tool for designing age-based dosing regimens for antimalarial drugs for drug registration and field use. Bulletin of the World Health Organization 2006;84:956-964. Resume Utilisation de donnees statistiques sur le poids en fonction de l'age pour optimiser le dosage des comprimes et les schemas posologiques pour une nouvelle association artesunate/amodiaquine en proportions fixes, destinee a traiter le paludisme a falciparum Objectif Tester une nouvelle methodologie permettant de definir les schemas posologiques en fonction de l'age pour le traitement du paludisme par une nouvelle association artesunate/amodiaquine en proportions fixes, conditionnee en plaquettes thermoformees et d'usage facile. Methodes Nous avons constitue une base de donnees de reference sur le poids en fonction de l'age a partir de donnees relatives a 88 054 individus, tirees d'Enquetes Demographiques et de Sante et d'etudes d'intervention et standardisees pour l'age, le sexe et le risque de paludisme. Nous avons ensuite determine le dosage optimal des comprimes [milligrammes (mg) par comprime] et les categories de dose par tranche d'age pour l'association artesunate/amodiaquine. Pour les differentes tranches d'age et les differents dosages par comprime, nous avons elabore des previsions estimatives des proportions de malades qui recevront des doses situees dans les plages therapeutiques nouvellement definies pour l'amodiaquine (7 a 15 mg/kg/j) et l'artesunate (2 a 10 mg/kg/j), a partir de modeles utilisant la base de donnees de reference pour le poids en fonction de l'age. Resultats Les dosages optimaux des comprimes a utiliser en pediatrie (p) et chez l'adulte (a) pour l'association artesunate/ amodiaquine etaient respectivement 25/67,5 et 100/270 mg. Un schema therapeutique prevoyant cinq tranches d'age :0-1 mois (1/2 p), 2-11 mois (1 p), 1-5 ans (2 p), 6-13 ans (1 a) et [superieur ou egal a] 14 ans (2 a) presentait une precision posologique globale de 83,4 % pour l'amodiaquine et de 99,9 % pour l'artesunate. Conclusion La methode proposee pour exploiter des donnees de reference sur le poids en fonction de l'age provenant de pays d'endemie palustre fournit un moyen utile a la definition des schemas posologiques en fonction de l'age pour des antipaludiques, en vue de l'homologation et de l'usage sur le terrain de ces medicaments. Resumen Uso del peso para la edad para optimizar la potencia de los comprimidos y la posologia de una nueva combinacion de dosis fijas de artesunato-amodiaquina para tratar la malaria por P. falciparum Objetivo Ensayar una nueva metodologia para definir los regimenes de dosificacion basados en la edad para el tratamiento de la malaria con una nueva combinacion de dosis fijas de artesunato y amodiaquina, facil de usar y suministrada en forma de blisteres. Metodos Se compilo una base de datos de referencia del peso para la edad de 88 054 personas del Africa subsahariana a partir de datos de las Encuestas de Demografia y Salud y estudios observacionales y de intervencion, que se normalizaron en funcion del sexo, la edad y el riesgo de malaria. A partir de ahi se determino la potencia optima de los comprimidos (miligramos (mg) por comprimido) y las categorias de edad-dosis para la combinacion de artesunato y amodiaquina. Utilizando modelos basados en la base de datos de referencia del peso para la edad, se estimaron, para diferentes categorias de edad y potencias (mg) de los comprimidos, las proporciones de pacientes que recibirian dosis situadas dentro de los margenes terapeuticos recien definidos para la amodiaquina (7-15 mg/kg/dia) y el artesunato (2-10 mg/kg/dia). Resultados La potencia optima pediatrica (p) y para adultos (a) de los comprimidos fue de 25/67,5 y 100/270 mg de artesunatol amodiaquina, respectivamente. Un regimen basado en cinco categorias de edad (0-1 meses (1/2 p), 2-11 meses (1 p), 1-5 anos (2 p), 6-13 anos (1 a), y [mayor que o igual a] 14 anos (2 a)) mostro una precision de dosificacion global del 83,4% y 99,9% para la amodiaquina y el artesunato, respectivamente. Conclusiones El metodo propuesto para usar datos de referencia del peso para la edad de los paises con malaria endemica constituye una valiosa herramienta para disenar regimenes de dosificacion basados en la edad para los antimalaricos con miras al registro de medicamentos y a su uso sobre el terreno., Introduction Rapid access to diagnosis and effective treatment is essential in the drive to roll back malaria. (1) Following the results of multicentre, proof of principle, clinical trials of artesunate [...]

The emergence and spread of drug-resistant malaria parasites is the major threat to effective malaria control. So far, malaria control has relied heavily on a restricted number of chemically related drugs belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin-type compounds been used widely, predominantly in Southeast Asia. Experience has shown that resistance eventually curtails the life span of antimalarial drugs. If measures are not applied to contain resistance, the investment put into the development of new drugs will be squandered. Current efforts focus, on the one hand, on research into novel compounds with mechanisms of action that are different to the traditionally used drugs, and, on the other hand, on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and expensive ventures. Whilst very few new antimalarial drugs were developed in the last quarter of the 20th century (only four of the nearly 1400 drugs registered worldwide during 1975-1999), various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial pipeline is relatively healthy. Projects are underway at different stages of drug development, from pre-development to registration. However, there is relatively little novelty, as current development projects still rely upon the traditional quinoline, antifolate and, in particular, artemisinin compounds. New structures are expected from the more upstream discovery efforts but it will take time before they become drugs. Therefore, whilst waiting for the drugs of tomorrow, there is a pressing need for immediately available, effective and affordable drugs that will have long life spans. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focussed on the use of artesunate combined with currently used standard drugs, namely mefloquine, amodiaquine, sulfadoxine/ pyrimethamine and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and are dependent on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. Malaria control programmes need efficacious drugs that can be used with ease by the populations of endemic countries. This review will summarise current antimalarial drug developments and outline recent clinical research that aims to bring artemisinin-based combinations to those that need them most. [ABSTRACT FROM AUTHOR]

Studies the use of azithromycin for malaria prophylaxis in Irian Jaya, Indonesia. New drugs needed for the prevention of drug-resistant Plasmodium falciparum malaria; Dosage of azithromycin.

This article presents a case study of dengue fever and long thoracic nerve palsy in a traveler from Thailand. On admission, he was febrile but there were no remarkable physical signs reported. Routine hematology revealed a normal hemoglobin level, leukopenia and mild thrombocytopenia. A blood film for malaria was negative. During hospitalization, the patient remained normotensive and did not develop an erythematous or petechial rash, signs of bleeding, pleural effusion, ascites, altered mental status or convulsion. A hemogram shows stable leukopenia, worsening thrombocytopenia and a mildly increased hemoglobin level. The levels of liver transaminases were raised. Anti-dengue virus IgM and IgG were reported to be positive. Two weeks later, the patient consulted a travel clinic because of fatigue, persistent pain, and the development of reduced elevation of his right arm, which had started one week earlier. The diagnosis revealed the patient developed an acute febrile illness for which have good epidemiologic, clinical and serologic evidence for a diagnosis of classic dengue fever due to dengue virus serotype 1. His illness was complicated by a right-sided thoracic nerve palsy that took more than four months to show signs of improvement and by nine months had not quite fully recovered.