Escolar con malaria por plasmodium falciparum de África: riesgo para la salud pública en Honduras / School child with Plasmodium falciparum malaria from Africa: public health risk in Honduras

Antecedentes: Los viajes a zonas endémicas con parásitos resistentes, la respuesta evolutiva de Plasmodium y los sistemas sanitarios debilitados, comprometen el control mundial y local de la malaria. Descripción del Caso clínico: Niño, 6 años, atendido en Hospital Escuela Universitario (HE), Tegucigalpa, referido desde Siguatepeque, Comayagua, por dudas en diagnóstico de laboratorio y antecedente de vivir en África y cuatro episodios de malaria por P. falciparum (2015-2017). Al ingreso presentó cuadro entérico e informe de Plasmodium spp. Se inició tratamiento con cloroquina, omitida y substituida al día siguiente por derivado de artemisinina al confirmar P. falciparum y 0.7% de eritrocitos parasitados. Presentó buena respuesta clínica y parasitológica, egresando al 7mo día intrahospitalario después de 72 horas afebril. La gota gruesa al egreso informó estadios sexuales de P. falciparum, administrándose primaquina al estar disponible 7 días después. En control ambulatorio al 5to día post-egreso, no se observaron parásitos aunque persistían leucocitos con pigmento malárico fagocitado. Cuatro familiares convivientes en África fueron examinados. El padre, que informó cefalea leve y febrícula, fue detectado con estadios asexuales de P. falciparum; presentó buena respuesta al tratamiento con derivado de artemisinina. Conclusiones: La descripción del caso y los diferentes eslabones en su manejo clínico y epidemiológico, reflejan la potencialidad de complicación de la malaria. La introducción de parásitos resistentes a la cloroquina constituye una amenaza de salud pública, principalmente ante fallas evitables en el sistema sanitario. Es necesario fortalecer el diagnóstico temprano y tratamiento oportuno especialmente en el contexto de la eliminación de malaria en Mesoamérica...(AU)

Malaria grave en unidad de cuidados intensivos: Reporte de un caso de una especie no endémica en Norte de Santander, Colombia / Severe Malaria in the Intensive Care Unit: The report of a Case of a Non-Endemic Species in North of Santander, Colombia / Malária grave na unidade de terapia intensiva: Informe de um caso de um tipo não endêmica no estado de Norte de Santander, na Colômbia

Introducción: La malaria es una enfermedad infecciosa vectorial de predominio en regiones tropicales y subtropicales. Existen 5 serotipos de Plasmodium, en Colombia se encuentran dos serotipos para malaria endémica, P. vivax y P. falciparum. Norte de Santander es una zona endémica para P. vivax. Objetivo: Presentación de un caso de malaria grave importada por P. falciparum, con una breve descripción de los aspectos fisiopatológicos de la malaria grave y los advenimientos de las nuevas terapias antipalúdicas. Presentación del caso: Paciente masculino de 45 años procedente de una región endémica para P. falciparum, que ingresó por cuadro febril inespecífico, trombocitopenia severa, alteración de la función renal y hepática con deterioro de su estado general. Es trasladado a la unidad de cuidados intensivos como urgencia dialítica, se diagnóstica malaria grave por P. falciparum, es tratado con antimaláricos y se reporta posible coinfección para el virus del dengue por inmunoglobulina M positiva (IgM), recibe terapia de reemplazo renal. Se contextualiza bajo un círculo vicioso en la disfunción de órganos, estructurado entre la insuficiencia renal y la insuficiencia respiratoria aguda con incremento de la permeabilidad vascular e hipoxemia refractaria, pese al esfuerzo terapéutico fallece por falla orgánica múltiple, por malaria grave. Conclusiones: La malaria es un problema en el área de salud pública, en nuestro caso corresponde a una malaria importada ya que en el departamento de Norte de Santander no se ha identificado dicho serotipo. [Ortiz-Ruiz G, Urbina-Contreras ZE, Lamos-Duarte AF, Ferreira MF, García-Zambrano F. Malaria grave en unidad de cuidados intensivos: Reporte de un caso de una especie no endémica en Norte de Santander, Colombia. MedUNAB 2017-2018; 20(3): 383-392].

Introduction: Malaria is a vector-borne infectious disease which is predominant in tropical and subtropical regions. There are 5 serotypes of Plasmodium, in Colombia there are two serotypes for endemic malaria, P. vivax and P. falciparum. North of Santander is an endemic area for P. vivax. Objective: To show a case of severe malaria caused by P. falciparum, with a brief description of the pathophysiological aspects of severe malaria and the advent of new antimalarial therapies. Case Presentation: A 45- year-old male patient from an endemic region with P. falciparum, who was admitted due to nonspecific febrile symptoms, severe thrombocytopenia, impaired renal and hepatic functions with deterioration of his general condition. He is transferred to the intensive care unit as a dialytic urgency. Severe malaria due to P. falciparum was diagnosed, he is treated with antimalarial medication, and a possible coinfection is reported for the dengue virus due to a positive immunoglobulin M (IgM) result, so he receives a renal replacement therapy. The case is contextualized in a vicious circle of organ dysfunction, which is structured between renal failure and acute respiratory failure with an increased vascular permeability and refractory hypoxemia; despite the therapeutic effort, the patient dies due to multiple organ failures, and severe malaria. Conclusions: Malaria is a problem in the public health area. This case corresponds to imported malaria because this serotype has not been identified yet in the department of North of Santander. [Ortiz- Ruiz G, Urbina-Contreras ZE, Lamos-Duarte AF, Ferreira MF, García-Zambrano F. Severe Malaria in the Intensive Care Unit: The report of a Case of a Non-Endemic Species in North of Santander, Colombia. MedUNAB 2017-2018; 20(3): 383-392].

Introdução: A malária é uma doença infecciosa vetorial predominantemente nas regiões tropicais e subtropicais. Existem 5 sorotipos de Plasmodium, na Colômbia existem dois sorotipos para malária endêmica, P. vivax e P. falciparum. O estado de Norte de Santander é uma região endêmica para P. vivax. Objetivo:Apresentação de um caso de malária grave importado por P. falciparum, com uma breve descrição dos aspectos fisiopatológicos da malária grave e o advento das novas terapias anti-maláricas. Apresentação do caso: Paciente do sexo masculino de 45 anos de uma região endêmica do P. falciparum, admitido com sintomas febris não específicados, trombocitopenia grave, insuficiência renal e função hepática, num estado geral deteriorado. Ele é transferido para a unidade de cuidados intensivos como emergência de diálise, é diagnosticada a malaria grave causada pelo P. falciparum, ele é tratado com antimaláricos e se reporta uma posível co-infecção pelo vírus da dengue pela imunoglobulina M (IgM) positiva, recebe então, tratamento de reposição renal. É contextualizado num círculo vicioso na disfunção dos órgãos, estruturado entre insuficiência renal e insuficiência respiratória aguda com aumento da permeabilidade vascular e hipoxemia refractária, apesar do esforço terapêutico morre devido à falência múltipla de órgãos, gerada pela malária grave. Conclusões: A malária é um problema na área da saúde pública, no nosso caso corresponde a uma malária importada, já que no departamento de Norte de Santander este serótipo não foi identificado. [Ortiz-Ruiz G, Urbina-Contreras ZE, Lamos- Duarte AF, Ferreira MF, García-Zambrano F. Malária grave na unidade de terapia intensiva: Informe de um caso de um tipo não endêmica no estado de Norte de Santander, na Colômbia. MedUNAB 2017-2018; 20(3): 383-392].

Blackwater Fever Followed by Severe Falciparum Malaria in a Child

Blackwater fever is a serious clinical syndrome manifested by acute intravascular hemolysis, fever, and the passage of black or red urine, which is classically associated with falciparum malaria and irregular administration of quinine. In Korea, Plasmodium vivax is the only endemic malaria circulating; a number of imported cases of falciparum malaria have been reported in patients following return from international travel to a malaria endemic area. Therefore, it is important for health care professionals including pediatricians to be aware of the falciparum malaria and its clinical courses. Herein, we report a case of a 14-year-old girl with severe falciparum malaria that was complicated by blackwater fever.

Antimaláricos a partir de moléculas obtidas por síntese como análogos de cloroquina e compostos naftoquinoidais / Antimalarials from molecules obtained by synthesis as chloroquine analogues and compounds naftoquinoidais

A resistência de Plasmodium falciparum aos antimaláricos esquizonticidas sanguíneos disponíveis, como a atovaquona e derivados de artemisinina, e a de P. vivax à cloroquina (CQ), exige a busca por alternativas quimioterápicas, objetivo deste trabalho. Como estratégia geradora de novos protótipos antimaláricos, foram feitas modificações estruturais (i) na CQ, as quais resultaram em 10 análogos de cloroquina (AnCQ), sendo quatro complexados com platina (AnCQPt), com atividade previamente descrita na malária pelo P. berghei; (ii) na atovaquona, originando oito naftoquinonas; e (iii) no lapachol, resultando em 11 compostos naftoquinoidais. Essas classes de moléculas foram avaliadas in vitro quanto a sua citotoxicidade (MCL50) e atividade antiplasmodial (IC50) contra parasitos sensíveis(S) ou resistentes(R) à CQ. Os índices de seletividade (IS), expressos pela razão entre essas duas atividades biológicas, foram obtidos. Os AnCQ foram mais ativos contra P. falciparum CQ-R in vitro e mais ativos que os AnCQPt e mostraram IS superiores ao da CQ. Para elucidar seu modo de ação, os AnCQ foram avaliados in silico quanto à ancoragem molecular na lactato-desidrogenase de P. falciparum(PfLDH) ou humana (HssLDH)...

Impact of G6PD deficiency on plasmodium falciparum malaria / 实用医学杂志

Objective To investigate the impact of Glucose-6-phosphate dehydrogenase (G6PD) deficiency on plasmodium falciparum malaria. Methods A cross-sectional study was performed on 2 690 patients in Malabo regional hospital on Bioko Island during rainy season (2012). The plasmodium falciparum was identified by real-time PCR and oil immersion microscopy. G6PD deficiency was identified by a fluorescent spot test (FST) and PCR-DNA sequencing. Logistic regression was conducted to estimate the association between G6PD deficiency and malaria. Results The prevalence of G6PD was 9.22% in the population , all of whose genotype G6PD deficiency was G6PD*A-(c.202 G > A/c.376 A > G). Confounding factors-adjusted OR showed that G6PD deficiency provided significant protection against malaria (P 0.05). Conclusions The results suggest that male hemizygotes could provide protection against malaria. Further studies are required to explore the molecular mechanism in malaria infection.

Malária falciparum com comprometimento renal (síndrome nefrótica - relato de caso / Falciparum malaria with renal impairment (nephrotic syndrome) - case report

Objetivo: apresentação de um caso de síndrome nefrótica por malária falciparum. Relato decaso: escolar, 8 anos, sexo feminino, admitida no Hospital Municipal de Tailândia, Pará, comquadro de febre alta, seguida de surgimento de edema, urina escura e oligúria.. Evoluiu comanúria e foi transferida para a Fundação Santa de Misericórdia do Pará (FSCM-PA), onderecebeu diagnóstico de síndrome nefrótica secundária à malária por Plasmodium falciparum,com base em dados de anamnese, exame físico e exames complementares. A paciente obteveboa resposta clínica e parasitológica com a terapêutica antimalárica, recebendo alta hospitalarpara controle no Programa de Ensaios Clínicos em Malária do Instituto Evandro Chagas eAmbulatório de Nefrologia. Considerações finais: o acometimento renal é uma dascomplicações graves da malária com possível evolução para insuficiência renal aguda (IRA), eque pode ser fatal. Desenvolvimento de estratégias preventivas de combate aos distúrbios renaisassociados à malária requer conhecimento dos aspectos clínicos e epidemiológicos da doença,diagnóstico precoce e correto, além de terapêutica antimalárica.

Objective: presentation of nephrotic syndrome case due to falciparum malaria. Case report:school child, 8 years old, female, admitted at Municipal Hospital of Tailândia, Pará, with historyof fever, edema, dark urine and oliguria. Because the patient evolved with anuria, she wastransferred to Fundação Santa Casa de Misericórdia do Pará (FSCM-PA), where she wasdiagnosed with nephrotic syndrome secondary to Plasmodium falciparum malaria, based onanamnesis, physical examination, and laboratory exams. The patient had clinical andparasitological response to antimalarial therapy, being discharged to control at Clinical EssayMalaria Program at Evandro Chagas Institute and in a Nephrology Outpatient Unit. Finalconsideration: renal involvement is one of the serious complications of malaria. It can progressto acute renal failure (ARF), and may be fatal. Development of preventive strategies againstkidney disorders due to malaria infection requires knowledge of epidemiological and clinicalfeatures of the disease, accurate and prompt diagnosis and antimalarial therapy.

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.

Factores no biológicos relacionados con el desarrollo de resistencia de Plasmodium falciparum a la cloroquina / Non-biological factors related to the development of resistance to chloroquine in Plasmodium falciparum

El desarrollo de resistencia de Plasmodium falciparum a los antimaláricos constituye unproblema importante para el control de la malaria. Particularmente, el surgimiento y dispersión de cepas de P. falciparum resistentes a la cloroquina a partir de la segunda mitad delsiglo XX representan un nuevo problema para su control. La literatura científica ha documentado factores relacionados con el hospedero humano, el vector, el parásito y el tratamiento que podríanexplicar la selección, supervivencia y dispersión local o a distancia de estas cepas. En esta revisión se exploraron factores no biológicos que intentan explicar el surgimiento y dispersión de cepas P. falciparum resistentes a la cloroquina. El entendimiento de los factores que contribuyen al surgimientode la resistencia a antimaláricos, es importante para el diseño de estrategias que busquen retardar la aparición de resistencia a nuevos antimaláricos.

The development of Plasmodium falciparum resistantto antimalarial drugs constitutes a major public health issue for malaria control. Particularly,the emergence and widespread of chloroquine resistant P. falciparum strains in the second half ofXX century represents a new challenge to malaria control. The scientific literature has documentedfactors related to the human host, the vector, the parasite and the treatment, which could explainthe selection, survival and local or wide spread of these strains. In this paper are reviewed non-biologicalfactors that could explain the emergencyof P. falciparum resistant chloroquine strains. The understanding of these factors is relevant to designstrategies to delay the emergence of antimalarial drug resistant parasites.

In-vitro Sensitivity of Plasmodium falciparum to the Components of Dihydroartemisinin Compounds in Dongfang City of Hainan Province / 广州中医药大学学报

[Objective] To examine the sensitivity of P. falciparum to the components of dihydroartemisinin (DHA) and piperaquine (PQ) in Dihydroartemisinin Compounds. [Methods] WHO (World Health Organization) standard micro test and in-vitro test were used. [Results] Survey in the year of 2001 for 61 cases and in 2004 for 28 cases showed that the DHA-resistant rate of P. falciparum in all cases was zero with inhibitory concentration of 50% (IC50) being 6.84 nmol/L and 5.67 nmol/L, and the mean concentration for complete inhibition of schizont formation was 35 nmol/L and 39 nmol/L, respectively. Survey in the year of 2001 for 75 cases and in 2004 for 29 cases showed that PQ-resistant rate of P. falciparum was 22.67% and 17.24% with IC50 being 274 nmol/L and 317 nmol/L, and the mean concentration for complete inhibition of schizont formation was 1 220 nmol/L and 1 269 nmol/L, respectively. [Conclusion] No DHA -resistance exists and PQ-resistance decreases for the treatment of P. falciparum in Dongfang city of Hainan province.

Timothy M.E. Davis, Janet Cox - Singh, Sean Hewitt. Treatment of uncomplicated falciparum malaria in Southern Vietnam: can chloroquine or sulfadoxine - pyrimethamine be introduced in combination with artesunate

The efficacy of chloroquine or sulfadoxine-pyrimethamine given combined with artesunate was assessed in Vietnamese patients with uncomplicated falciparum malaria from 2 Southern provinces, where there was in vitro evidence that the sensitivity of the parasite to conventional antimalarial therapies had returned in the absence of drug pressure, from October to December of 2000. In Dak Lak province, 57 patients (mean age 9.6 years) were randomized to artesunate-chloroquine (group 1) or artesunate-sulfadoxine/pyrimethamine (group 2). In Binh Phuoc province, 66 patients, who have just migrated in period of 1-7 years (mean age 24.2 years) were assessed with the 2 regimens. The results of 28 days in vivo response were over 96% and lower 52% of Dak Lak and Binh Phuoc respectively. PCR evidence of cure closely paralleled the in vivo results. The successful reintroduction of chloroquine and sulfadoxine-pyrimethamine as artemisinin partner drugs depends heavily on epidemiological and parasite factors

Randomized clinical trials of dihydroartemisinin - piperaquine against multidrug resistant

A clinical randomized trial on dihydroartemisinin piperaquin was conducted with drug resistant malaria patients. The effectiveness to cure the disease through 56 days follow up the recurrent by PCR manifested on 97.4% in DTP group and 100% in A3M group. In second study the rate of recovery was equal in all groups - DTP group 97.4%; DP group 98.7%; A3M group 98.7%. Dihydroartemisenin piperaquin was well tolerated. In less than 3% of patients, there was side effects which can be related to smoking. The preparation is inexpensive, effective, safe with high efficacy to drug resistant malaria parasite.

Comparative Studies on Effects of Dihydroartemisinin and Quinine on Plasmodium Falciparum Gametocytes at Early Stage / 广州中医药大学学报

Objective To study the effects of dihydroartemisinin and quinine on plasmodium falciparum gametocytes at early stage. Methods Eleven patients with falciparum malaria who had plasmodium falciparum gametocytes at early stage(PFGe) in bone marrow but no matured plasmodium falciparum gametocytes(PFGm) in bone marrow and peripheral blood were allocated to two groups.Group A(n=6) were administered orally with dihydroartemisinin at a total dosage of 480mg for 7 days and Group B(n=5) with quinine sulfate at a total dosage of 10?500 mg for 7 days.The number of gametocytes in bone marrow and peripheral blood was examined at regular time. Results PFGe in bone marrow disappeared in Group A on 10 th day after the first administration while existed in all the cases of Group B on 10 th day and still in 2 cases on 14 th day.The clearance time for peripheral PFGe was 4.8?0.9 days in Group A and 22.0?5.8 days in Group B. Conclusion Dihydroartemisinin can clear PFGe but quinine shows no this action.

Randomized Controlled Trial of Two Kinds of Compound Dihydroartemisinin with or Without Trimethoprim for Uncomplicated Falciparum Malaria / 广州中医药大学学报

0.05).The cure rate was 100%and parasite recrudescence rate was zero in both groups,the difference being insignificant.The incidence of adverse reaction was lower in Artekin group.【Conclusion】Artecom and Artekin have similar therapeutic effect on uncomplicated falciparum malaria,but Artekin without trimethoprim has lower adverse reactions,thus it is recommended for clinical use.

A Study of Artemether Combined with Primaquine in the Treatment of Falciparum malaria / 中国寄生虫学与寄生虫病杂志

Objective To evaluate the efficacy and side effects of artemether combined with primaquine in the treatment of falciparum malaria. Methods Randomization and comparison methods were used in 121 falciparum malaria cases in the Republic of Central Africa.Sixty one cases were treated with artemether combined with primaquine(Group A used artemether orally,Group B used artemether intramuscularly).And 60 cases received single artemether (Group C used artemether orally,Group D used artemether intramuscularly ) were taken as control. Results In Group A and B the mean fever clearance time were 47 6?15 7 and 36 9?10 7 hours, clinical cure rates 84 4% and 100%, relapse rates 6 3% and 3 4% ,respectively.In Group C and D the mean fever clearance time were 48 2?18 4 and 42 2?9 5 hours,clinical cure rates 90 1% and 96 3%, relapse rates 21 2% and 18 5%,respectively.Side effects in cases of all groups were mild. Conclusion Artemether combined with primaquine and single artemether(via both routes) showed good therapeutic effects in falciparum malaria cases, while artemether combined with primaquine was more effective than single artemether in reducing relapes rate of malaria.