Genetic polymorphisms of CYP2B6*6, CYP2C8*3 and CYP2D6*4 in vivax malaria patients from Brazilian Amazon

Abstract Genetic variability in the host metabolism of antimalarial drugs influenced by the polymorphisms of cytochrome P450 (CYP) could lead to significant changes in antimalarial treatment response. However, little is known about the frequency of alleles CYP2B6, CYP2C8, and CYP2D6 in an Amazonian population, especially with vivax malaria. Therefore, this study aimed to determine the frequency of CYP alleles CYP2B6*6, CYP2C8*3, and CYP2D6*4 in patients with vivax malaria. The study included 231 patients with vivax malaria treated at a health care reference in Manaus, northern Brazil. A sample of peripheral blood from each subject was collected to perform DNA extraction and genotypic analysis. Genotyping of polymorphisms was performed by allelic discrimination using Real-time polymerase chain reaction. The CYP2D6*4 allele was the most prevalent among patients who developed severe malaria. The frequencies of the CYP2B6*6 and CYP2D6*4 were not different between the severe and uncomplicated malaria. There was a significant association between heterozygous CYP2D6*4 and severe cases of malaria. The results are in agreement with other reports described in the literature for different populations. Future studies are needed to understand the clinical implications of the polymorphisms in patients with vivax malaria.

COVID-19 pandemic: challenges ahead / Pandemia de COVID-19: retos por enfrentar

Abstract Since December 2019, health systems worldwide have faced the pandemic caused by the new severe acute respiratory syndrome coronavirus 2. The pandemic began in China and has spread throughout the world. This new coronavirus has a high transmission capacity and elevated lethality in people over 60 years old and in those with risk factors (obesity, diabetes, and systemic arterial hypertension); those characteristics have a different proportion in each country. At present, there is no specific, effective, and safe treatment to treat this virus. In this review, an analysis is made on the differences in epidemiological aspects of the disease and its presentation in pediatric patients; the poorly-based recommendation for using an empirical combination of antimalarials plus antimicrobials as antiviral treatment; the indication of intravenous steroids; and the possible influence of antihypertensive drugs on the course of the disease.

Resumen A partir de diciembre de 2019, los sistemas de salud de todos los países se han enfrentado a la pandemia causada por un nuevo coronavirus (SARS-CoV-2), el cual fue notificado por primera vez en China y se ha esparcido por todo el mundo. Este nuevo coronavirus posee una alta capacidad para transmitirse. A escala mundial la letalidad ha sido más alta en la población mayor de 60 años y en aquellos que tienen factores de riesgo (obesidad, diabetes e hipertensión arterial sistémica). Sin embargo, estas características varían en proporción en cada país. Hasta el momento no hay un tratamiento específico, eficaz y seguro para combatir este virus. En este artículo se realiza un análisis sobre las diferencias globales en los aspectos epidemiológicos y con relación a su presentación en pacientes pediátricos, así como de la recomendación, con pobre fundamento, del uso de la combinación de antimaláricos y antimicrobianos empíricos como antivirales. También se analizan la indicación de esteroides intravenosos y la posible influencia de los fármacos antihipertensivos en el curso de la enfermedad.

Position statement from the Brazilian Society of Nephrology regarding chloroquine and hydroxychloroquine drug dose adjustment according to renal function / Nota da Sociedade Brasileira de Nefrologia em relação ao ajuste das drogas cloroquina e hidroxicloroquina pela função renal

ABSTRACT Chloroquine and hydroxychloroquine have shown promising preliminary results and have been discussed as therapeutic options for patients with Covid-19. Despite the lack of robust evidence demonstrating the benefits and justifying the use of one of these drugs, the final decision is the responsibility of the attending physician and should be individualized and shared, whenever possible. This position statement recommends dosage adjustment for these drugs in the context of renal impairment.

RESUMO Em razão de resultados preliminares promissores, a hidroxicloroquina e a cloroquina têm sido discutidas como opção terapêutica para pacientes com Covid-19. Apesar da ausência de estudos robustos que evidenciem o benefício e justifiquem o uso de uma dessas drogas, a decisão final compete ao médico assistente, devendo ser individualizada e, sempre que possível, compartilhada. A presente nota pretende orientar o ajuste posológico dessas drogas no contexto da disfunção renal.

Terapia medicamentosa para infecções por coronavírus em humanos: revisão sistemática rápida / Pharmacological therapies for patients with human coronavirus infections: a rapid systematic review

Resumo O objetivo deste trabalho foi avaliar efeitos de tratamentos medicamentosos para infecções por coronavírus. Revisão sistemática rápida com buscas nas bases MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov e International Clinical Trials Registry Platform. Foram incluídos 36 estudos avaliando alternativas medicamentosas contra SARS, SARS-CoV-2 e MERS. A maioria dos estudos incluídos foi conduzida na China com delineamento observacional para tratamento da COVID-19. Os tratamentos mais estudados foram antimaláricos e antivirais. Nos antimaláricos, a metanálise de dois estudos com 180 participantes não identificou benefício da hidroxicloroquina em relação à negativação da carga viral via reação em cadeia de polimerase em tempo real e o uso de antivirais comparado ao cuidado padrão foi similar em relação aos desfechos. As evidências científicas disponíveis são preliminares e de baixa qualidade metodológica, o que sugere cautela na interpretação dos dados. Pesquisas que avaliem a eficácia comparativa em ensaios clínicos randomizados, controlados, com tempo de acompanhamento adequado e com os métodos devidamente divulgados e sujeitos à revisão científica por pares são necessárias. Recomenda-se atualização periódica da presente revisão.

Abstract This work aimed to evaluate the effects of drug therapies for coronavirus infections. Rapid systematic review with search in the MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov and International Clinical Trials Registry Platform databases. Thirty-six studies evaluating alternative drugs against SARS, SARS-CoV-2 and MERS were included. Most of the included studies were conducted in China with an observational design for the treatment of COVID-19. The most studied treatments were with antimalarials and antivirals. In antimalarial, the meta-analysis of two studies with 180 participants did not identify the benefit of hydroxychloroquine concerning the negative viral load via real-time polymerase chain reaction, and the use of antivirals compared to standard care was similar regarding outcomes. The available scientific evidence is preliminary and of low methodological quality, which suggests caution when interpreting its results. Research that evaluates comparative efficacy in randomized, controlled clinical trials, with adequate follow-up time and with the methods properly disclosed and subject to scientific peer review is required. A periodic update of this review is recommended.

Impacto de diferentes esquemas terapéuticos sobre la malaria en la costa y amazonia peruana, en el marco de una política de medicamentos antimaláricos, 1994-2017 / Impact on the transmission of malaria with different treatment schemes in the peruvian coast and amazon region within the framework of a policy on antimalarial medications, 1994-2017

RESUMEN Al final de los 90 en el Perú, después de determinar la resistencia a antimaláricos, se decidió el cambio de los esquemas terapéuticos antimaláricos, que incluía la terapia combinada para P. falciparum, mefloquina/artesunato en la amazonia y sulfadoxina pirimetamina/artesunato en la costa norte. Luego de dos décadas, con el objetivo de evaluar el impacto en la endemia de malaria de estos esquemas, se revisaron los reportes de malaria en tres departamentos que juntos agrupan más del 70% de los casos reportados en el país. Fue evidente el mayor impacto del esquema sulfadoxinapirimetamina/artesunato en costa norte reduciendo a casi cero los casos de P. falciparum luego de cuatro años de implementar terapia combinada. La monodosis y la capacidad de limitar el desarrollo de esporozoitos fueron importantes para conseguir este objetivo. El esquema mefloquina/artesunato tuvo impacto limitado por la imposibilidad de asegurar tratamiento supervisado en los servicios de salud y la necesidad de tres dosis. Seleccionar un esquema eficaz y de fácil administración es importante al elegir la primera línea de tratamiento para malaria. Esta experiencia es significativa para los objetivos de eliminación de la malaria en el Perú.

ABSTRACT At the end of the 90s in Peru, after determining the resistance to antimalarial drugs, a change in antimalarial treatment schemes was decided; this change included the combined therapy for P. falciparum, mefloquine/artesunate in the Amazon region, and sulfadoxine pyrimethamine/artesunate in the North coast. After two decades, and aimed at assessing the impact of these schemes on the malaria endemic, a review was conducted of malaria reports in three departments accounting for more than 70% of cases reported in the country. The major impact of the sulfadoxine-pyrimethamine/ artesunate scheme in the North coast was evident since it reduced the number of cases of P. falciparum to virtually zero four years after implementation of the combined therapy. The single dose and the ability to limit the development of sporozoites were crucial in order to achieve this goal. The mefloquine/artesunate scheme had a limited impact because it was not possible to ensure supervised treatment in the health service facilities and the need for three doses. It is important to select an effective and easy-to-administer scheme when choosing the first line of treatment for malaria. This experience is significant for the malaria eradication goals in Peru.

Assistência Farmacêutica em Moçambique: a ajuda externa na provisão pública de medicamentos / Pharmaceutical Services in Mozambique: foreign aid in public provision of medicines

Resumo Este artigo analisa a ação de atores nacionais e internacionais na Assistência Farmacêutica (AF) em Moçambique, no período de 2007 a 2012, com foco na provisão pública de medicamentos para HIV/Aids, malária e tuberculose. Descreve-se o funcionamento da AF no país; os atores que atuam nesse âmbito e as relações entre eles; discutem-se questões relevantes sobre o modus operandi dos parceiros de cooperação. A metodologia combinou: revisão bibliográfica, levantamento e análise documental e entrevistas. O marco teórico e analítico utilizou a análise de políticas públicas com foco no papel do Estado e suas inter-relações como os demais atores na ajuda externa na área farmacêutica e a abordagem de redes. Conclui-se que a interação entre os atores envolvidos é complexa, caraterizada pela fragmentação operacional e sobreposição de atividades entre diversos entes; centralização da aquisição de medicamentos na mão de poucos agentes; by pass das estruturas nacionais e desconsideração do necessário fortalecimento do sistema nacional de saúde para a construção de sua autonomia. A despeito de alguns avanços na provisão e disponibilidade de medicamentos para essas doenças, existe forte dependência externa nesse âmbito, o que obstaculiza a sustentabilidade da AF em Moçambique.

Abstract This article examines the activities of national and international actors in Pharmaceutical Services (PS) in Mozambique from 2007 to 2012, focusing on the public provision of HIV/Aids, malaria and tuberculosis medicines. It describes how PS functions in the country, what actors are involved in this area and the relations among them, pursuing salient issues in the modus operandi of partners in cooperation. The methodology combines literature review, document survey and analysis and interviews. The theoretical and analytical framework was given by the policy analysis approach, focusing on the role of the State and its interrelations with other actors in foreign aid in PS, and also by the networks approach. It was concluded that the interactions among the actors involved is complex and characterised by operational fragmentation and overlapping of activities between entities, centralised medicine procurement in the hands of few agents, bypassing of national structures and disregard for the strengthening needed to bolster national health system autonomy. Despite some advances in the provision and availability of medicines for these diseases, external dependence is strong, which undermines the sustainability of PS in Mozambique.

Malaria on the Guiana Shield: a review of the situation in French Guiana

In a climate of growing concern that Plasmodium falciparum may be developing a drug resistance to artemisinin derivatives in the Guiana Shield, this review details our current knowledge of malaria and control strategy in one part of the Shield, French Guiana. Local epidemiology, test-treat-track strategy, the state of parasite drug resistance and vector control measures are summarised. Current issues in terms of mobile populations and legislative limitations are also discussed.

Plasmodium vivax malaria elimination: should innovative ideas from the past be revisited?

In the 1950s, the strategy of adding chloroquine to food salt as a prophylaxis against malaria was considered to be a successful tool. However, with the development of Plasmodium resistance in the Brazilian Amazon, this control strategy was abandoned. More than 50 years later, asexual stage resistance can be avoided by screening for antimalarial drugs that have a selective action against gametocytes, thus old prophylactic measures can be revisited. The efficacy of the old methods should be tested as complementary tools for the elimination of malaria.

Emerging Plasmodium vivax resistance to chloroquine in South America: an overview

The global emergence of Plasmodium vivax strains resistant to chloroquine (CQ) since the late 1980s is complicating the current international efforts for malaria control and elimination. Furthermore, CQ-resistant vivax malaria has already reached an alarming prevalence in Indonesia, East Timor and Papua New Guinea. More recently, in vivo studies have documented CQ-resistant P. vivax infections in Guyana, Peru and Brazil. Here, we summarise the available data on CQ resistance across P. vivax-endemic areas of Latin America by combining published in vivo and in vitro studies. We also review the current knowledge regarding the molecular mechanisms of CQ resistance in P. vivax and the prospects for developing and standardising reliable molecular markers of drug resistance. Finally, we discuss how the Worldwide Antimalarial Resistance Network, an international collaborative effort involving malaria experts from all continents, might contribute to the current regional efforts to map CQ-resistant vivax malaria in South America.

In vivo Study of Antiplasmodial Activity of Terminalia avicennioides and Its Effect on Lipid Profile and Oxidative Stress in Mice Infected with Plasmodium berghei.

Aims: To determine the antiplasmodial activity of methanolic extract of T. avicennioides and its effect on oxidative stress and the lipid profiles in mice infected with Plasmodium berghei. Study Design: Mice used for this study were grouped into five. The first group was not infected with malaria parasite (normal control), the second group was infected with the parasite but not treated with antimalarial drugs (negative control), the third group was infected with the parasite and treated with 5mg/kg body weight of artesunat (positive control), while the fourth and fifth groups were infected with malaria parasite and treated with 100 and 200mg/kg of T. avicennioides respectively. Methodology: The parasitaemia was monitored for five days. The animals were sacrificed on the fifth day and the blood was collected. The serum was used to assess the biochemical parameters using randox kits. Results: While parasite density increases in the negative control per day, there was reduction in parasite density in treated groups. The parasite clearance was significantly higher (P = .05) in those treated with 200mg/kg of T. avicennioides than those treated with 100mg/kg of T. avicennioides and 5mg/kg of artesunat. The malondialdehyde level was significantly higher in the negative control, while superoxide dismutase and catalase levels were significantly reduced when compared with group treated with 200mg/kgbdwt of T. avicennioides. HDL level was significantly higher (P = .05) in those treated with 200mg/kg than in the normal, negative and positive control. The triglycerides level was significantly higher in the negative control when compared with the group treated with the extract of T. avicennioides. Conclusion: This study showed that the methanolic extract of T. avicennioides display dose-related in vivo antiplasmodial and antioxidant activities as well as reduced the serum and liver lipoprotein cholesterol in mice infected with P. berghei.

Modulation of cerebral malaria by curcumin as an adjunctive therapy

Cerebral malaria is the most severe and rapidly fatal neurological complication of Plasmodium falciparum infection and responsible for more than two million deaths annually. The current therapy is inadequate in terms of reducing mortality or post-treatment symptoms such as neurological and cognitive deficits. The pathophysiology of cerebral malaria is quite complex and offers a variety of targets which remain to be exploited for better therapeutic outcome. The present review discusses on the pathophysiology of cerebral malaria with particular emphasis on scope and promises of curcumin as an adjunctive therapy to improve survival and overcome neurological deficits.

Possible artemisinin-based combination therapy-resistant malaria in Nigeria: a report of three cases

Artemisinin-based combination therapy-resistant malaria is rare in Sub-Saharan Africa. The World Health Organization identifies monitoring and surveillance using day-3 parasitaemia post-treatment as the standard test for identifying suspected artemisinin resistance. We report three cases of early treatment failure due to possible artemisinin-based combination therapy-resistant Plasmodium falciparum malaria. All cases showed adequate clinical and parasitological responses to quinine. This study reveals a need to re-evaluate the quality and efficacy of artemisinin-based combination therapy agents in Nigeria and Sub-Saharan Africa.

A Case of Vivax Malaria Complicated by Adult Respiratory Distress Syndrome and Successful Management with Extracorporeal Membrane Oxygenation

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.

Artesunate + amodiaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in the Colombian Pacific region: a noninferiority trial / Artesunato + amodiaquina versus artemether-limefantrina para o tratamento da malaria não complicada por Plamodium falciparum no Pacifico Colombiano: um estudo de não inferioridade

INTRODUCTION: In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. METHODS: A randomized, controlled, open-label, noninferiority (Δ≤5%) clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28‑day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. Safety: assessed through adverse events. RESULTS: A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval) adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%). There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group), typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group) was significantly shorter (p=0.002). Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68) and 1% and 13.3% after treatment (p<0.001). CONCLUSIONS: Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.

INTRODUÇÃO: Na Colômbia não existem estudos publicados sobre o tratamento da malária não complicada por Plasmodium falciparum comparando as terapias combinadas com artemisinina. Destarte, quer se demonstrar a não inferioridade dos perfis de eficácia/segurança dos tratamentos com artesunato+amodiaquina versus artemeter-lumefantrina. MÉTODOS: Foi realizado um estudo clínico de não inferioridade (∆≤5%), aleatório, controlado, aberto, em adultos com malária não complicada por P. falciparum usando o desenho validado de 28 dias e os desenhos validados/definidos pela Organização Mundial da Saúde. Os pacientes foram aleatorizados (1:1) para ambos artesunato+amodiaquina ou artemeter-lumefantrina orais. Critérios primários de eficácia: resposta clínica e parasitológica adequada; Criterios de eficácia secundários: as falhas de tratamento definidos pela Organização Mundial da Saúde. A segurança: avaliada através de eventos adversos. RESULTADOS: Foram incursos 105 pacientes em cada grupo: zero observações censuradas. As taxas médias da resposta clínica e parasitológica adequada (95% IC - intervalo de confiança): 100% para artesunato+amodiaquina e 99% para artemeter-lumefantrina; atingiu-se o critério de não inferioridade (∆=1.7%). Houve uma falha terapêutica parasitológica tardia (1%; grupo artemeter-lumefantrina), caracterizada mediante reação em cadeia da polimerase como o alelo MAD20 MSP1. Tempo de remissão da febre (grupo artesunato+amodiaquina), foi significativamente mais curto (p=0.002). Dor abdominal, para artesunato+amodiaquina e artemeter-lumefantrina, respectivamente, 1.9% e 3.8% (p=0.68) na linha de base, 1% e 13.3% pós-tratamento (p<0.001). CONCLUSÕES: O tratamento com artesunato+amodiaquina da malária não complicada por P. falciparum é não inferior ao tratamento normal com artemeter-lumefantrina. Os perfis de eficácia/segurança justificam estudos adicionais nesta e outras populações semelhantes.

Hemophagocytic syndrome associated with Plasmodium falciparum infection.

Hemophagocytic syndrome (HPS) has been associated with infections, hematological malignancies and autoimmune conditions. Malaria is rarely reported to cause HPS. We report a case of an 11-month-old infant with fever, hepatosplenomegaly, pancytopenia, high serum ferritin, hypertriglyceridemia, and bone marrow hemophagocytosis, consistent with hemophagocytic syndrome. Gametocytes of plasmodium falciparum were identified on bone marrow aspiration. Rapid recovery was observed after treatment with antimalarials.

Metemoglobinemia em pacientes com malária por Plasmodium vivax em uso oral de primaquina / Methemoglobinemia in patients with Plasmodium vivax receiving oral therapy with primaquine

INTRODUÇÃO: A primaquina pode acarretar sérios eventos adversos, com destaque para a toxicidade ao sangue. O objetivo deste trabalho é determinar a metemoglobinemia de 20 pacientes com malária por Plasmodium vivax tratados com primaquina, comparando-os segundo o sexo e a expressão da glicose-6-fosfato desidrogenase. MÉTODOS: Quantificação da metemoglobina por espectrofotometria visível e avaliação qualitativa da glicose-6-fosfato desidrogenase. RESULTADOS: A metemoglobinemia variou de 2,85 a 5,45 por cento nos pacientes do sexo masculino e de 3,77 a 7,34 por cento no feminino. CONCLUSÕES: A instituição da terapia aumentou de maneira significativa os teores de metemoglobina, sem manifestação clínica evidente e independente do sexo e da atividade enzimática.

INTRODUCTION: Primaquine can produce adverse reactions as toxicity to blood when used in the treatment of vivax malaria. This work aimed to determine methemoglobinemia in patients with vivax malaria receiving oral therapy with primaquine. METHODS: Spectrophotometric quantification of methemoglobinemia and qualitative assay for glucose-6-phosphate dehydrogenase. RESULTS: Methemoglobinemia ranged from 2.85 to 5.45 percent in male patients and 3.77 to 7.34 percent in female patients. CONCLUSIONS: A statistically significant increase in methemoglobinemia was observed following oral therapy with primaquine, with no clinical manifestations, and independent of sex and the qualitative expression of glucose-6-phosphate dehydrogenase.

Plan de mejoramiento del control de la malaria hacia su eliminación en Mesoamérica / Plan to improve malaria control towards its elimination in Mesoamerica

Desarrollar un plan de fortalecimiento del control de la mala-ria hacia su eliminación. En 2009, bajo la coordinación del Instituto Nacional de Salud Pública, se integró un equipo técnico transdisciplinario para hacer un diagnóstico situacional de la malaria y de los programa de control y para la selección de prácticas efectivas de intervención que serían incorporadas al plan, en el marco de un ejercicio de teoría de cambio. Se establecieron criterios de estratificación de las localidades con base en sus condiciones de transmisión. Se identificaron limitaciones estructurales y operativas de los programas de control. Se elaboró un plan de intervenciones para mejorar la cobertura de vigilancia epidemiológica, intervenciones antimaláricas y diagnóstico y tratamiento oportunos de casos. El plan delinea con fases progresivas de implementación: reorganización, intensificación de intervenciones y evaluación de la factibilidad de eliminación. La adopción de un plan estratégico único brindará lineamientos y elementos administrativos para conformar un sistema que coordine las actividades de los programas nacionales de control y facilite la eliminación de la malaria en la región.

To develop a plan to strengthen the control of malaria towards its elimination. In 2009, under the coordination of the National Public HealthInstitute ofMexico, atransdisciplinary equipment of technical and operative experts was conformed to carry out a situational analysis of malaria and control programs and for the selection of effective practices of intervention that would be incorporated to the plan, within the framework of an exercise in Theory of Change. Criteria for thestratificationof thelocalities, based ontheirtransmission characteristics were established. The structural and operative limitations of the control programs were identified. A plan of interventions was elaborated to improve the coverage of epidemiological surveillance, anti-malaria interventions and opportune diagnosis and treatment of cases. The plan delineates progressive phases of implementation: reorganization, intensification of interventions and evaluation of elimination feasibility. The adoption of a regional strategic plan will provide guidance and administrative elements to conform a system that coordinates the activities of the national control programs and facilitate the elimination of malaria in the region.

Subdoses of primaquine in overweight patients and malaria vivax relapses: report of two cases in the Federal District, Brazil / Subdoses de primaquina associadas a recaídas de malária vivax em pacientes com peso elevado: relato de dois casos no Distrito Federal

Two cases of malaria by Plasmodium vivax relapsed after treatment with drugs in doses recommended by the Ministry of Health are presented. Both patients were overweight and were followed in the Federal District, an area considered free from vector transmission of the disease. Radical cure was obtained after medication with the same drugs in weight proportional doses.

São apresentados dois casos de pacientes com malária por Plasmodium vivax que apresentaram recaídas após tratamento com medicamentos em doses indicadas pelo Ministério da Saúde. Ambos os pacientes tinham pesos elevados e foram acompanhados no Distrito Federal, área considerada sem transmissão vetorial da doença. A cura radical foi obtida após medicação em dose proporcional ao peso corpóreo dos pacientes.

Tratamiento antimalárico: una revisión actualizada / Antimalarious treatment: an up-to-date review

Con el propósito de ofrecer una panorámica sobre las drogas antimaláricas desde su surgimiento hasta la situación actual, se realiza una revisión actualizada que incluye una breve reseña histórica sobre la evolución que ha experimentado el tratamiento antipalúdico desde antes de Nuestra Era hasta la fecha actual. Se reflejó la introducción de las principales drogas en el manejo terapéutico de la enfermedad. También se describió el fenómeno de la resistencia a las drogas antimaláricas como problema para alcanzar el control de dicha afección, haciendo referencia a su definición, clasificación, factores y mecanismos que intervienen en la misma, así como su desarrollo cronológico y la situación mundial actual referente a la drogoresistencia. Además se mostraron las principales drogas antimaláricas usadas actualmente con sus dosis y vías de administración, y cuáles son las tendencias contemporáneas que recomiendan su utilización. Finalmente se relacionaron las perspectivas que tiene para el futuro el tratamiento antimalárico acorde con el nivel actual de conocimientos y las últimas investigaciones realizadas. Se concluyó que las estrategias terapéuticas deben fundamentarse en los niveles de resistencia existente en las diferentes zonas geográficas, utilizando combinaciones de drogas antipalúdicas, sobre todo aquellas que incluyan algún derivado del artemisinín, y si esto no es posible al menos usar racionalmente combinaciones de otras acorde al nivel de resistencia de la región.

With the purpose of offering a panoramic on antimalarial drugs from their emergence until the current situation, an up-to-date review was carried out that includes a brief historical review on the evolution that has experienced the antimalarial treatment from before Christ to date. The introduction of the main drugs in the therapeutic handling of the disease was reflected. The phenomenon of the resistance to the antimalarial drugs as problem to reach the control of this affection was also described, making reference to its definition, classification, factors and mechanisms that intervene, as well as its chronological development and the current world situation concerning to the drug-fast. The main antimalarial drugs currently used with their doses and administration pathways were also shown, and which are the contemporary tendencies that recommend their use. Finally the perspectives that have for the future the antimalarious treatment with the current level of knowledge were related and the last carried out investigations. We concluded that the therapeutic strategies should be based in the existent resistance levels in the different geographical areas, using combinations of antimalarial drugs, mainly those that include some derived of the artemisinin, and if this is not possible at least to use some other combinations rationally according to the resistance level of the region.