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Braz. j. biol ; 83: e247422, 2023. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1285631


Abstract Plasmodium falciparum resistance to Chloroquine (CQ) is a significant cause of mortality and morbidity worldwide. There is a paucity of documented data on the prevalence of CQ-resistant mutant haplotypes of Pfcrt and Pfmdr1 genes from malaria-endemic war effected Federally Administered Tribal Areas of Pakistan. The objective of this study was to investigate the prevalence of P. falciparum CQ-resistance in this area. Clinical isolates were collected between May 2017 and May 2018 from North Waziristan and South Waziristan agencies of Federally Administrated Trial Area. Subsequently, Giemsa-stained blood smears were examined to detect Plasmodium falciparum. Extraction of malarial DNA was done from microscopy positive P. falciparum samples, and P. falciparum infections were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes). All PCR confirmed P. falciparum samples were sequenced by pyrosequencing to find out mutation in Pfcrt gene at codon K76T and in pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y. Out of 121 microscopies positive P. falciparum cases, 109 samples were positive for P. falciparum by nested PCR. Pfcrt K76T mutation was found in 96% of isolates, Pfmdr1 N86Y mutation was observed in 20%, and 11% harboured Y184F mutation. All samples were wild type for Pfmdr1 codon N1042D and D1246Y. In the FATA, Pakistan, the frequency of resistant allele 76T remained high despite the removal of CQ. However, current findings of the study suggest complete fixation of P. falciparum CQ-resistant genotype in the study area.

Resumo A resistência do Plasmodium falciparum à cloroquina (CQ) é uma causa significativa de mortalidade e morbidade em todo o mundo. Há uma escassez de dados documentados sobre a prevalência de haplótipos mutantes CQ-resistentes dos genes Pfcrt e Pfmdr1 da guerra endêmica da malária em áreas tribais administradas pelo governo federal do Paquistão. O objetivo deste estudo foi investigar a prevalência de resistência a CQ de P. falciparum nesta área. Isolados clínicos foram coletados entre maio de 2017 e maio de 2018 nas agências do Waziristão do Norte e do Waziristão do Sul da Área de Ensaio Administrada Federalmente. Posteriormente, esfregaços de sangue corados com Giemsa foram examinados para detectar Plasmodium falciparum. A extração do DNA da malária foi feita a partir de amostras de P. falciparum positivas para microscopia, e as infecções por P. falciparum foram confirmadas por nested PCR (visando genes de ácido ribonucleico ribossômico de subunidade pequena de Plasmodium (ssrRNA)). Todas as amostras de P. falciparum confirmadas por PCR foram sequenciadas por pirosequenciamento para descobrir a mutação no gene Pfcrt no códon K76T e em pfmdr1 nos códons N86Y, Y184F, N1042D e D1246Y. De 121 microscopias de casos positivos de P. falciparum, 109 amostras foram positivas para P. falciparum por nested PCR. A mutação Pfcrt K76T foi encontrada em 96% dos isolados, a mutação Pfmdr1 N86Y foi observada em 20% e 11% abrigou a mutação Y184F. Todas as amostras eram do tipo selvagem para o códon N1042D e D1246Y de Pfmdr1. No FATA, Paquistão, a frequência do alelo resistente 76T permaneceu alta apesar da remoção de CQ. No entanto, as descobertas atuais do estudo sugerem a fixação completa do genótipo resistente a CQ de P. falciparum na área de estudo.

Plasmodium falciparum/genetics , Antimalarials/pharmacology , Pakistan , Membrane Transport Proteins/genetics , Drug Resistance/genetics , Protozoan Proteins/genetics , Chloroquine/pharmacology , Multidrug Resistance-Associated Proteins/genetics , Alleles
Rev. Eugenio Espejo ; 16(1): 71-80, 20220111.
Article in Spanish | LILACS | ID: biblio-1353005


Objetivo. Determinar el estado actual de la prevalencia de Plasmodium en pacientes febriles que acuden al Hospital Básico Franklin Tello Nuevo Rocafuerte, cantón Aguarico, comparando con los datos de otros estudios epidemiológicos de la misma zona y la frontera con el vecino país de Perú. Métodos. Se realizó un estudio observacional descriptivo, retrospectivo de prevalencia. Desde 2011-2015 se recogieron 2.668 muestras de sangre capilar correspondientes al 55,04% de la población total del cantón Aguarico. Se empleó la técnica Gota Gruesa y Frotis coloreados con Giemsa para determinar positividad de Plasmodium. Resultados. El rango de variación de la prevalencia en los pobladores de las comunidades investigadas osciló entre 2,38% y 28,57%, detectándose mayor prevalencia en el sexo masculino (50,56 %). Estos hallazgos son similares a los estudios previos realizados entre 1992-1995, en la misma región del Aguarico. El Riesgo Relativo es (RR) es de 1,36 y el Odds Ratio (OR) fue de 1,71, siendo mayor el riesgo a desarrollar la enfermedad en los positivos. Conclusiones. Los datos de la investigación confirman la presencia de un foco autóctono de malaria producida por Plasmodium vivax en la selva amazónica ecuatoriana, excepto 2 casos de P. falciparum importados de Perú. Los casos diagnosticados clínicamente y mediante la técnica de la Gota Gruesa, fueron tratados con medicación antipalúdica con excelente adherencia al medicamento.

Objective. To determine the status of the prevalence of Plasmodium in febrile patients who attend the Franklin Tello Nuevo Rocafuerte Basic Hospital, Aguarico town, comparing the results obtained with data from other epidemiological studies in the same area, and places near the border with Peru. Methods. A descriptive, retrospective, observational study of prevalence was carried out. From 2011-2015 2,668 capillary blood samples were collected corresponding to 55.04% of the total population of the Aguarico town. The Thick Drop and Giemsa-stained smear technique was used to determine Plasmodium positivity. Results. The range of variation of the prevalence in the inhabitants of the investigated communities ranged between 2.38% and 28.57%, detecting a higher prevalence in males (50.56%). These findings are like previous studies carried out between 1992-1995, in the same Aguarico region. The Relative Risk (RR) is 1.36 and the Odds Ratio (OR) was 1.71, with the risk of developing the disease being greater in the positives. Conclusions. The research data confirm the presence of an autochthonous focus of malaria produced by Plasmodium vivax in the Ecuadorian Amazon rainforest, except for 2 cases of P. falciparum imported from Peru. The cases diagnosed clinically and using the thick gout technique were treated with antimalarial medication with excellent adherence to the medication.

Humans , Male , Female , Prevalence , Amazonian Ecosystem , Malaria , Plasmodium vivax , Indigenous Peoples , Antimalarials
Research Journal of Heath Sciences ; 10(2): 112-120, 2022. figures, tables
Article in English | AIM, AIM | ID: biblio-1370670


Background: Nigeria adopted the Artemisinin-Based Combination Therapy (ACT) as the mainstay of treating uncomplicated malaria in February 2005. However, the individual preferences for the use of these medicines by health care professionals (HCP) as distinct from their observed prescribing practices is largely unknown. This study determined the preferences, tolerability and cost of the ACTs among HCP in Benin-City. Methods: This descriptive cross-sectional study was conducted in the University of Benin Teaching Hospital, Benin-City, Nigeria. Consenting HCPs were recruited consecutively for the study. Semi structured questionnaires were administered to doctors, nurses and pharmacists in the hospital. Information obtained included demographics, treatment of malaria in the previous year, antimalarial medication preferences and tolerability as well as cost of ACT. Results: A total of 556 HCPs, 295 doctors (54.1%), nurses 200 (36.0%), pharmacists 61(11.0%) completed the questionnaire. In the previous year, 224 (75.9%) doctors, 153 (79.1%) nurses, and 48 (70.5%) pharmacists had treatment for malaria and self-medication was highest among doctors (228,77.3%). Artemether-Lumenfantrine was the most preferred antimalarial used, 294 (52.8%); however, 1.6% used chloroquine sulphate and ACTs were perceived to be ineffective by 25.4%. Adverse effects were experienced by 167 (29.1%) resulting in 50 (9.0%) discontinuing their medication. Between 500 and 1500 Naira (~US$1-4) was expended on ACT by 66.3% of the staff, while 21.4% were concerned about the high cost of medications. Conclusion: This study highlights the use and preferences, self-medication practices, perceived lack of effectiveness and high cost of ACTs from a HCP perspective. There is an urgent need to address these concerns in view of adverse consequences as well as the likely possibility of its the impact on prescribing practices.

Therapeutics , Health Personnel , Artemisinins , Drug Therapy, Combination , Artemether, Lumefantrine Drug Combination , Malaria , Self Medication , Antimalarials
Article in Chinese | WPRIM | ID: wpr-888193


As a unicellular organism, Plasmodium displays a panoply of lipid metabolism pathways that are seldom found together in a unicellular organism. These pathways mostly involve the Plasmodium-encoded enzymatic machinery and meet the requirements of membrane synthesis during the rapid cell growth and division throughout the life cycle. Different lipids have varied synthesis and meta-bolism pathways. For example, the major phospholipids are synthesized via CDP-diacylglycerol-dependent pathway in prokaryotes and de novo pathway in eukaryotes, and fatty acids are synthesized mainly via type Ⅱ fatty acid synthesis pathway. The available studies have demonstrated the impacts of artemisinin and its derivatives, the front-line compounds against malaria, on the lipid metabolism of Plasmodium. Therefore, this article reviewed the known lipid metabolism pathways and the effects of artemisinin and its derivatives on these pathways, aiming to deepen the understanding of lipid synthesis and metabolism in Plasmodium and provide a theoretical basis for the research on the mechanisms and drug resistance of artemisinin and other anti-malarial drugs.

Antimalarials/pharmacology , Artemisinins/therapeutic use , Humans , Lipid Metabolism , Malaria/drug therapy , Plasmodium
Article in Chinese | WPRIM | ID: wpr-878980


Artemisiae Annuae Herba is a traditional Chinese medicine for clearing deficiency and heat. It is the only natural source of artemisinin, which is a specific antimalarial drug, and has been widely concerned all over the world. In addition to artemisinin, Artemisiae Annuae Herba also contains many sesquiterpenes, coumarins, flavonoids, volatile oils, polysaccharides and other chemical components, which show antipyretic, anti-inflammatory, antiviral microorganisms, anti-asthma, anti-oxidation, anti-tumor and other pharmacological activities. In addition to their own pharmacological activities, some components could enhance the antimalarial activity of artemisinin through different mechanisms at absorption and metabolism in vivo. In order to understand the pharmacokinetic characte-ristics of the chemical constituents contained in Artemisiae Annuae Herba and provide reference for the full development and clinical utilization of Artemisiae Annuae Herba resources in China, this present paper systematically collated the modern research literatures, and summarized the biosynthesis, in vivo analysis and pharmacokinetics of the chemical constituents in Artemisiae Annuae Herba.

Antimalarials , China , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Oils, Volatile
J. venom. anim. toxins incl. trop. dis ; 27: e20200073, 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1154769


he resistance against antimalarial drugs represents a global challenge in the fight and control of malaria. The Brazilian biodiversity can be an important tool for research and development of new medicinal products. In this context, toxinology is a multidisciplinary approach on the development of new drugs, including the isolation, purification, and evaluation of the pharmacological activities of natural toxins. The present study aimed to evaluate the cytotoxicity, as well as the antimalarial activity in silico and in vitro of four compounds isolated from Rhinella marina venom as potential oral drug prototypes. Methods: Four compounds were challenged against 35 target proteins from P. falciparum and screened to evaluate their physicochemical properties using docking assay in Brazilian Malaria Molecular Targets (BraMMT) software and in silico assay in OCTOPUS® software. The in vitro antimalarial activity of the compounds against the 3D7 Plasmodium falciparum clones were assessed using the SYBR Green I based assay (IC50). For the cytotoxic tests, the LD50 was determined in human pulmonary fibroblast cell line using the [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Results: All compounds presented a ligand-receptor interaction with ten Plasmodium falciparum-related protein targets, as well as antimalarial activity against chloroquine resistant strain (IC50 = 3.44 µM to 19.11 µM). Three of them (dehydrobufotenine, marinobufagin, and bufalin) showed adequate conditions for oral drug prototypes, with satisfactory prediction of absorption, permeability, and absence of toxicity. In the cell viability assay, only dehydrobufotenin was selective for the parasite. Conclusions: Dehydrobufotenin revealed to be a potential oral drug prototype presenting adequate antimalarial activity and absence of cytotoxicity, therefore should be subjected to further studies.(AU)

Bufanolides/administration & dosage , Bufonidae , Biodiversity , Malaria/immunology , Antimalarials , In Vitro Techniques , Computer Simulation
Article in English | AIM, AIM | ID: biblio-1293117


Objectives: In 2018, malaria claimed an estimated 380,000 lives in African region, with Nigeria accounting for 24.0% (91,368) of malaria deaths from the region. Mutations in Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and P. falciparum multidrug resistance 1 (Pfmdr-1) genes had reduced the effective use of artemisinin combination therapy through the development of resistance to these antimalarial agents. Our study set out to determine the antimalarial drug resistance polymorphisms in Pfcrt and Pfmdr-1 genes of P. falciparum isolates among patients in Kano State, Nigeria. Material and Methods: Malaria positive samples were collected across the three senatorial districts of Kano State. The samples were amplified using nested polymerase chain reaction to detect the Pfcrt and Pfmdr-1 genes. The amplicons were sequenced and bioinformatic analysis was done using CLC Sequence viewer 8.0 and BioEdit sequence alignment editor to detect the single-nucleotide polymorphisms. Results: In the Pfcrt gene, CVIET haplotype was seen in 26.2% of the samples while only two samples showed the 86Y mutation in the Pfmdr-1 gene. All the 86Y mutations and majority of the CVIET haplotypes were detected in the patients from rural settings where some of them noted that they consumed modern and traditional (herbs) antimalarial agents. One sample was observed to have the CVIET haplotype and N86Y mutation while the other five CVIET haplotypes were seen in five separate samples. A new mutation V62A was found in the Pfmdr-1 gene as observed in one of the sample. Conclusion: It is imperative to ensure the rational use of the right antimalarial agents and employ continuous resistance surveillance/mapping to ensure synergy in malaria containment and elimination strategies.

Humans , Plasmodium falciparum , Polymorphism, Genetic , Malaria, Falciparum , Antimalarials , Nigeria
Rev. Soc. Bras. Med. Trop ; 54: e05362020, 2021. tab, graf
Article in English | LILACS | ID: biblio-1155593


Abstract INTRODUCTION: Artemisinin-based combination therapy (ACT), such as artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL), is the first-line treatment for malaria in many malaria-endemic areas. However, we lack a detailed evaluation of the cardiotoxicity of these ACTs. This study aimed to analyze the electrocardiographic effects of these three ACTs in malaria patients. METHODS: We analyzed the clinical data of 89 hospitalized patients with falciparum malaria who had received oral doses of three different ACTs. According to the ACTs administered, these patients were divided into three treatment groups: 27 treated with AP (Artequick), 31 with DP (Artekin), and 31 with AL (Coartem). Electrocardiograms and other indicators were recorded before and after the treatment. The QT interval was calculated using Fridericia's formula (QTcF) and Bazett's formula (QTcB). RESULTS: Both QTcF and QTcB interval prolongation occurred in all three groups. The incidence of such prolongation between the three groups was not significantly different. The incidence of both moderate and severe prolongation was not significantly different between the three groups. The ΔQTcF and ΔQTcB of the three groups were not significantly different. The intra-group comparison showed significant prolongation of QTcF after AL treatment. CONCLUSIONS: Clinically recommended doses of DP, AL, and AP may cause QT prolongation in some malaria patients but do not cause torsades de pointes ventricular tachycardia or other arrhythmias.

Humans , Malaria, Falciparum/drug therapy , Artemisinins/adverse effects , Malaria/drug therapy , Antimalarials/adverse effects , Quinolines , Drug Combinations , Electrocardiography , Artemether/therapeutic use , Artemether, Lumefantrine Drug Combination/therapeutic use
Braz. J. Pharm. Sci. (Online) ; 57: e181086, 2021. tab, graf
Article in English | LILACS | ID: biblio-1350237


Malaria is nowadays one of the most serious health concerns in a global scale and, although there is an evident increase in research studies in this area, pointed by the vast number of hits and leads, it still appears as a recurrent topic every year due to the drug resistance shown by the parasite exposing the urgent need to develop new antimalarial medications. In this work, 38 molecules were synthesized via copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) or "click" chemistry, following different routes to produce 2 different organic azides, obtained from a 4,7 dicholoquinoline, reacted with 19 different commercially available terminal alkynes. All those new compounds were evaluated for their in vitro activity against the chloroquine resistant malaria parasite Plasmodium falciparum (W2). The cytotoxicity evaluation was accomplished using Hep G2 cells and SI index was calculated for every molecule. Some of the quinoline derivatives have shown high antimalarial activity, with IC50 values in the range of 1.72-8.66 µM, low cytotoxicity, with CC50>1000 µM and selectivity index (SI) in the range of 20-100, with some compounds showing SI>800. Therefore, the quinolinotriazole hybrids could be considered a very important step on the development of new antimalarial drugs

In Vitro Techniques/instrumentation , Chloroquine/administration & dosage , Malaria/drug therapy , Antimalarials/analysis , Plasmodium falciparum/metabolism , Research/classification , Drug Resistance/drug effects , Chimera/abnormalities , Inhibitory Concentration 50 , Click Chemistry
Rev. bras. parasitol. vet ; 30(1): e022120, 2021. tab, graf
Article in English | LILACS | ID: biblio-1156221


Abstract Neospora caninum is an apicomplexan parasite that causes abortion in cattle, resulting in significant economic losses. There is no commercial treatment for neosporosis, and drug repositioning is a fast strategy to test possible candidates against N. caninum. In this article, we describe the effects of atovaquone, chloroquine, quinine, primaquine and tetracycline on N. caninum proliferation. The IC50 concentrations in N. caninum were compared to the current information based on previous studies for Plasmodium and Toxoplasma gondii, correlating to the described mechanisms of action of each tested drug. The inhibitory patterns indicate similarities and differences among N. caninum, Plasmodium and T. gondii. For example, atovaquone demonstrates high antiparasitic activity in all the analyzed models, while chloroquine does not inhibit N. caninum. On the other hand, tetracycline is effective against Plasmodium and N. caninum, despite its low activity in T. gondii models. The repurposing of antimalarial drugs in N. caninum is a fast and inexpensive way to develop novel formulations using well-established compounds.

Resumo Neospora caninum é um parasita Apicomplexa relacionado a abortos no gado bovino, que resultam em impactos econômicos. Não há tratamento comercial para neosporosis e o reposicionamento de drogas indica uma estratégia rápida para testar candidatos anti-N. caninum. Neste artigo, são descritos os efeitos da atovaquona, cloroquina, quinino, primaquine e tetraciclina na proliferação de N. caninum. As concentrações IC50 em N. caninum foram comparadas com a informação disponível, baseada em estudos publicados previamente para Plasmodium e Toxoplasma gondii, incluindo a correlação com os mecanismos de ação descritos para cada droga testada. Os padrões de inibição indicam pontos de similaridades e diferenças entre N. caninum, Plasmodium e T. gondii. Por exemplo, a atovaquona demonstra uma alta atividade antiparasitária em todos os modelos testados, enquanto a cloroquina não inibe N. caninum. Por outro lado, a tetraciclina é efetiva contra Plasmodium e N. caninum, em contraste com a baixa atividade em modelos de T. gondii. O reposicionamento de drogas antimaláricas em N. caninum é uma forma rápida e de baixo custo para o desenvolvimento de novas formulações que usam compostos bem estabelecidos.

Neospora/drug effects , Antimalarials/pharmacology , Primaquine/pharmacology , Quinine/pharmacology , Tetracyclines/pharmacology , Chloroquine/pharmacology , Atovaquone/pharmacology
Rev. colomb. nefrol. (En línea) ; 7(supl.2): 194-210, jul.-dic. 2020. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1251585


Resumen Aunque es evidente el compromiso de los sistemas respiratorio y digestivo en los pacientes infectados por el nuevo coronavirus (SARS-CoV-2), también puede existir compromiso de otros sistemas importantes, como lo es el sistema renal. En este sentido, se hace imprescindible que el clínico no olvide que los pacientes renales muchas veces concomitan con enfermedades cardiovasculares, ya que en ambas patologías se torna sombrío el pronóstico de la enfermedad infectocontagiosa causada por este nuevo coronavirus. Aún no existen fármacos efectivos y aprobados para enfrentar este virus, pero se presume el posible efecto benéfico de los antimaláricos (hidroxicloroquina y cloroquina) y se espera que a través de las propiedades antivirales que exhiben estos fármacos se mejore el pronóstico y la mortalidad asociada a la enfermedad; al respecto se adelantan un número considerable de ensayos que escudriñan y discuten la viabilidad de este tratamiento. En el presente artículo se realiza una revisión narrativa de la evidencia científica disponible hasta el 15 de abril de 2020 en las bases de datos acerca del uso de este grupo de fármacos contra la COVID-19.

Abstract Although compromise of the respiratory and digestive systems is evident in patients infected with the new coronavirus (SARS-CoV-2), there may also be compromise of other important systems, such as the renal system. In this sense, it is essential that the clinician does not forget that kidney patients often coexist with cardiovascular diseases, since in both pathologies the prognosis of the infectious contagious disease caused by this new coronavirus becomes bleak. There are still no effective and approved drugs to face this virus, but the possible beneficial effect of antimalarials (hydroxychloroquine and chloroquine) is presumed and it is expected that the prognosis and mortality associated with these drugs will improve through the antiviral properties that these drugs exhibit. the illness; In this regard, a considerable number of trials are being conducted that scrutinize and discuss the feasibility of this treatment. This article makes a narrative review of the scientific evidence available until April 15, 2020 in the databases about the use of this group of drugs against COVID-19.

Humans , Male , Female , COVID-19 , Antimalarials , Antiviral Agents , Patients , Therapeutics , Colombia
Rev. chil. pediatr ; 91(5): 749-753, oct. 2020. graf
Article in Spanish | LILACS | ID: biblio-1144274


INTRODUCCIÓN: La malaria congénita (MC) es la infección por Plasmodium spp adquirida in útero o durante el parto y sus manifestaciones clínicas son inespecíficas. Puede causar enfermedad grave en la embaraza da y en el recién nacido. OBJETIVO: describir dos casos de MC causados por Plasmodium falciparum, diagnóstico diferencial de sepsis en recién nacidos de gestantes que hayan visitado o residan en áreas endémicas para malaria. CASOS CLÍNICOS: Neonatos de sexo femenino, nacidos en área no endémica para malaria, diagnosticados con sepsis neonatal y tratados con antibióticos sin respuesta clínica. Después de la primera semana de vida la gota gruesa identificó trofozoítos de Plasmodium falciparum y los neonatos recibieron tratamiento con quinina intravenosa con mejoría. Las madres de las recién nacidas tuvieron malaria en el embarazo, una de ellas recibió tratamiento y estaba asintomática y otra tenía malaria complicada al momento del parto. CONCLUSIONES: La MC puede causar enfermedad neonatal grave con manifestaciones clínicas inespecíficas y similares a la sepsis, el tratamiento oportuno disminuye el riesgo de malaria complicada. Es un diagnóstico diferencial en recién nacidos de mujeres con malaria durante el embarazo o gestantes que visiten o residan en áreas endémicas.

INTRODUCTION: Congenital malaria (CM) is a Plasmodium spp infection acquired in utero or during delivery with nonspecific clinical manifestations. Plasmodium falciparum can cause severe illness in pregnant wo men and newborns. OBJECTIVE: to describe two cases of CM caused by Plasmodium falciparum, di fferential diagnosis of sepsis in newborns of pregnant women who live in or have visited endemic malaria zones. CLINICAL CASES: Female neonates born in a non-endemic malaria area, diagnosed with neonatal sepsis and treated with antibiotics without clinical response. After the first week of life, the peripheral blood smear identified trophozoites of Plasmodium falciparum thus the newborns were treated with intravenous quinine, improving their condition. The mothers of the two newborns who had malaria in pregnancy, one of them received treatment and she was asymptomatic, and the other one had severe malaria at the time of delivery. CONCLUSIONS: CM can cause severe neonatal disease with non-specific, sepsis-like clinical manifestations in which early treatment decreases the risk of complicated malaria. It is a differential diagnosis in newborns of women with a history of malaria during pregnancy or pregnant women visiting or living in endemic malaria areas.

Humans , Female , Pregnancy , Infant, Newborn , Adolescent , Young Adult , Malaria, Falciparum/congenital , Malaria, Falciparum/diagnosis , Pregnancy Complications, Parasitic/diagnosis , Pregnancy Complications, Parasitic/drug therapy , Neonatal Sepsis/diagnosis , Malaria, Falciparum/transmission , Infectious Disease Transmission, Vertical , Diagnosis, Differential , Neonatal Sepsis/parasitology , Antimalarials/therapeutic use
Brasília; s.n; 17 jun. 2020.
Non-conventional in Portuguese | PIE, LILACS, BRISA, PIE | ID: biblio-1100423


O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 15 artigos.

Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Technology Assessment, Biomedical , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Heparin/therapeutic use , Lincomycin/therapeutic use , Azithromycin/therapeutic use , Ritonavir/therapeutic use , Angiotensin II Type 2 Receptor Blockers/therapeutic use , Lopinavir/therapeutic use , Interferon beta-1a/therapeutic use , Interferon beta-1b/therapeutic use , Interferon alpha-2/therapeutic use , Hydroxychloroquine/therapeutic use , Medicine, Chinese Traditional , Anti-Bacterial Agents/therapeutic use , Antimalarials/therapeutic use , Nitric Oxide/therapeutic use
Brasília; s.n; 13 maio 2020.
Non-conventional in Portuguese | PIE, LILACS, BRISA, PIE | ID: biblio-1097393


Essa é uma produção do Departamento de Ciência e Tecnologia (Decit) da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) do Ministério da Saúde (Decit/SCTIE/MS), que tem como missão promover a ciência e tecnologia e o uso de evidências científicas para a tomada de decisão do SUS, tendo como principal atribuição o incentivo ao desenvolvimento de pesquisas em saúde no Brasil, de modo a direcionar os investimentos realizados em pesquisa pelo Governo Federal às necessidades de saúde pública. Informar sobre as principais evidências científicas descritas na literatura internacional sobre tratamento farmacológico para a COVID-19. Além de resumir cada estudo identificado, o informe apresenta também uma avaliação da qualidade metodológica e a quantidade de artigos publicados, de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, entre outros). Foram encontrados 15 artigos e 10 protocolos.

Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Renin-Angiotensin System , Ribavirin/therapeutic use , Steroids/therapeutic use , Technology Assessment, Biomedical , Methylprednisolone/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Sulbactam/therapeutic use , Cefoperazone/therapeutic use , Chloroquine/therapeutic use , Plasmapheresis/instrumentation , Adrenal Cortex Hormones/therapeutic use , Azithromycin/therapeutic use , Disease Progression , Ritonavir/therapeutic use , Lopinavir/therapeutic use , Glucocorticoids/therapeutic use , Hydroxychloroquine/therapeutic use , Anticoagulants/therapeutic use , Antimalarials/therapeutic use
Int. j. morphol ; 38(2): 278-288, abr. 2020. graf
Article in English | LILACS | ID: biblio-1056435


This experiment was designed to study the effects of oral administration of artemether which is the most rapid-acting class of antimalarial drugs and the possible protective effect of vitamin E taken with it on the liver of albino rats. A total of twenty-four adult male albino rats were used in this study and were divided into four groups. Group one served as a control and rats in group two exposed to oral intake of artemether daily for fifteen days. The third and fourth groups treated with artemether plus low and high doses of vitamin E respectively. At the end of the experiment, the rats were sacrificed, and the livers were obtained and processed for histological, biochemical and statistical studies. Histological study of the hepatocytes of rats exposed to artemether showed nearly complete disintegration of most cellular contents except few numbers of mitochondria and rough endoplasmic reticulum. Also, the cytoplasm of these cells had few lysosomes, many vacuoles and irregular nuclei with abnormal distribution of chromatin and were shown. The hepatic sinusoids were dilated and filled with blood and vacuoles and bile ductules were abnormal in its structure. Treatment with low and high doses of vitamin E in concomitant with artemether ameliorated the hepatic histopathological lesions and its parenchyma attained nearly normal structure. As far as biochemical changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rats treated with artemether were significantly elevated as compared to the control. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were significantly increased in the liver in rats treated with artemether. However, vitamin E ameliorated the rise in ALT and AST with decreased MDA concentration and levels of SOD as compared to the corresponding artemether group values. Results of the present suggest that artemether has a harmful and stressful effect on hepatic tissue and the treatment with vitamin E may alleviate this toxicity.

Este experimento fue diseñado para estudiar los efectos de la administración oral de arteméter, la clase de medicamentos antipalúdicos de acción rápida, y el posible efecto protector de la vitamina E en el hígado de ratas albinas. Se utilizaron un total de 24 ratas albinas machos adultas y se dividieron en cuatro grupos. El grupo uno sirvió como control y las ratas en el grupo dos recibieron la dosis oral de arteméter diariamente durante 15 días. Los grupos tres y cuatro fueron tratados con arteméter, más dosis bajas y altas de vitamina E, respectivamente. Al final del experimento, se sacrificaron las ratas y se obtuvieron y procesaron los hígados para estudios histológicos, bioquímicos y estadísticos. El estudio histológico de los hepatocitos de ratas expuestas a arteméter mostró una desintegración casi completa de la mayoría de los contenidos celulares, excepto algunos mitocondrias y retículo endoplásmico rugoso. Además, el citoplasma de estas células tenía pocos lisosomas, muchas vacuolas y núcleos irregulares con distribución anormal de cromatina. Los sinusoides hepáticos estaban dilatados y llenos de sangre y vacuolas, y los conductos biliares tenían una estructura anormal. El tratamiento con dosis bajas y altas de vitamina E en forma concomitante con arteméter mejoró las lesiones histopatológicas hepáticas y su parénquima alcanzó una estructura casi normal. En cuanto a los cambios bioquímicos, la alanina aminotransferasa (ALT) y la aspartato aminotransferasa (AST) en ratas tratadas con arteméter se elevaron significativamente en comparación con el control. Los niveles de superóxido dismutasa (SOD) y malondialdehído (MDA) aumentaron significativamente en el hígado en ratas tratadas con arteméter. Sin embargo, la vitamina E mejoró el aumento de ALT y AST con una disminución de la concentración de MDA y los niveles de SOD en comparación con los valores correspondientes del grupo de arteméter. Los resultados del presente estudio sugieren que el arteméter tiene un efecto dañino y estresante sobre el tejido hepático y el tratamiento con vitamina E puede aliviar esta toxicidad.

Animals , Male , Rats , Vitamin E/pharmacology , Artemisinins/toxicity , Chemical and Drug Induced Liver Injury, Chronic/enzymology , Aspartate Aminotransferases/analysis , Vitamin E/administration & dosage , Microscopy, Electron, Transmission , Alanine Transaminase/analysis , Disease Models, Animal , Liver/drug effects , Antimalarials/toxicity
Int. j. morphol ; 38(2): 461-471, abr. 2020. graf
Article in English | LILACS | ID: biblio-1056463


This experiment was designed to study the administration of normal doses of one of recent antimalarial drug and coadministration of vitamin E on the kidney tissue. A total twenty-four adult male albino rats were used and divided into four groups: the first one served as a control, the second received artemether orally for three days consecutively. The rats of the third and fourth groups received the same dose of artemether concomitantly with 50 and 100 mg/kg vitamin E orally daily for 2 weeks. After the last dose, the rats were sacrificed and the kidney tissues with blood samples obtained and processed for light, electron microscopic and biochemical analysis. Histologically, artemether treated kidneys showed atrophied glomeruli with widened urinary space and kidney tubules were degenerated with disturbed contour and some vacuoles inside it. Ultrastructurally, the glomeruli of this group showed hypertrophic endothelial cells, irregularity of its basement membrane, disrupted foot processes and filtration slits. The kidney tubule cells showed loss of basal infoldings, cytoplasmic vacuolation, polymorphic damaged swollen mitochondria a loss of its microvilli towards its capillary lumen. Artemether plus vitamin E of the rat kidney groups showed improvement of morphological changes compared to the changes seen in artemether alone. These data were confirmed by biochemical findings with marked improvement of blood urea and creatinine levels and increase of anti-oxidant enzyme activities of glutathione peroxidase and superoxide dismutase in the vitamin E treated groups. The results of this study revealed that vitamins E can improve the adverse changes of artemether of rat renal tissue.

Este proyecto fue diseñado para estudiar la administración de dosis normales de uno de los medicamentos antipalúdicos y de la administración de vitamina E en el tejido renal. Se utilizaron 24 ratas albinas machos adultas divididas en cuatro grupos: el primero sirvió como control, el segundo recibió arteméter por vía oral durante tres días consecutivos. Las ratas del tercer y cuarto grupos recibieron la misma dosis de arteméter concomitantemente con 50 y 100 mg / kg de vitamina E por vía oral diariamente durante 2 semanas. Después de la última dosis, las ratas fueron sacrificadas y se obtuvo el tejido renal de cada muestra los cuales fueron procesados para análisis con microscopías de luz y electrónica, además de exámenes bioquímicos. Histológicamente, los riñones tratados con arteméter mostraron atrofia glomerular con espacio urinario ensanchado y túbulos renales degenerados con contorno alterado y algunas vacuolas en su interior. Ultraestructuralmente, los glomérulos de este grupo mostraron células endoteliales hipertróficas, irregularidad de su membrana basal, procesos alterados del pie y hendiduras de filtración. Las células del túbulo renal mostraron pérdida de inflexiones basales, vacuolación citoplasmática, mitocondrias dañadas y pérdida de sus microvellosidades hacia la luz capilar. Arteméter más vitamina E en los grupos de riñón de rata mostraron una mejora de los cambios morfológicos, en comparación con los cambios observados en arteméter solamente. Estos datos fueron confirmados por hallazgos bioquímicos con una marcada mejoría de los niveles de urea y creatinina en sangre y un aumento de las actividades enzimáticas antioxidantes de la glutatión peroxidasa y la superóxido dismutasa en los grupos tratados con vitamina E. Los resultados de este estudio revelaron que la vitamina E puede mejorar los cambios adversos del arteméter del tejido renal de la rata.

Animals , Male , Rats , Vitamin E/pharmacology , Acute Kidney Injury/chemically induced , Artemether/toxicity , Vitamin E/administration & dosage , Microscopy, Electron , Biomarkers/analysis , Rats, Wistar , Kidney/drug effects , Kidney/pathology , Kidney/ultrastructure , Antimalarials/toxicity
Ciênc. Saúde Colet ; 25(9): 3517-3554, Mar. 2020. tab, graf
Article in Portuguese | ColecionaSUS, LILACS, ColecionaSUS, SES-SP | ID: biblio-1133149


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, 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, 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.

Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Antiviral Agents/administration & dosage , Pneumonia, Viral/virology , Randomized Controlled Trials as Topic , Coronavirus Infections , Coronavirus Infections/virology , Severe Acute Respiratory Syndrome/virology , SARS Virus/isolation & purification , SARS Virus/drug effects , Pandemics , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Middle East Respiratory Syndrome Coronavirus/drug effects , Betacoronavirus , Betacoronavirus/isolation & purification , Betacoronavirus/drug effects , Antimalarials/administration & dosage
Mem. Inst. Oswaldo Cruz ; 115: e200229, 2020. tab, graf
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-1135249


Malaria and tuberculosis are no longer considered to be neglected diseases by the World Health Organization. However, both are huge challenges and public health problems in the world, which affect poor people, today referred to as neglected populations. In addition, malaria and tuberculosis present the same difficulties regarding the treatment, such as toxicity and the microbial resistance. The increase of Plasmodium resistance to the available drugs along with the insurgence of multidrug- and particularly tuberculosis drug-resistant strains are enough to justify efforts towards the development of novel medicines for both diseases. This literature review provides an overview of the state of the art of antimalarial and antituberculosis chemotherapies, emphasising novel drugs introduced in the pharmaceutical market and the advances in research of new candidates for these diseases, and including some aspects of their mechanism/sites of action.

Humans , Tuberculosis/drug therapy , Malaria/drug therapy , Antimalarials/therapeutic use , Antitubercular Agents/therapeutic use , Tuberculosis/diagnosis , Neglected Diseases , Malaria/diagnosis
Article in Chinese | WPRIM | ID: wpr-828091


Plasmodium culture in vitro is often used as an antimalarial drug evaluation model, but the lifecycle of P. falciparum culture in vitro tends to be disordered, which affects the research and evaluation of antimalarial drug mechanism in vitro. By combining magnetic bead separation method with sorbitol synchronization method, a synchronization method was constructed to quickly acquire different lifecycles of P. falciparum and obtain large amounts of parasite with a narrow synchronization window in a short period. Furthermore, the dihydroartemisinin(DHA) was used to treat the early trophozoite phase of P. falciparum 3 D7 for 4 h. Then mRNA was extracted and RNA-seq was conducted to analyze the differential expression of mRNA after drug treatment and obtain the differential gene expression profile. Differential expression of up-regulated genes and down-regulated genes was analyzed according to the screening criteria of |log_2FC|>1 and P<0.05. There, 262 genes were up-regulated and 77 genes were down-regulated. GO functional enrichment analysis of all the differentially expressed genes showed that the enrichment items mainly included cell membrane components, transporter activity, serine/threonine kinase activity, Maurer's clefts(MCs), rhoptry, antigen variation and immune evasion. The enrichment of KEGG pathway included malaria, fatty acid metabolism and peroxisome. Protein-protein interaction(PPI) analysis showed that the down-regulated genes in the modules with high degree of association included rhoptry, myosin complex, transporter and other genes related to the important life activities of malaria invasion and immune escape; the up-regulated genes were mainly related to various toxic exportins of malaria, such as PfSBP1 of MCs. qRT-PCR was used to verify the expression level of some genes, and most of the results were the same as the sequencing results. SBP1 was significantly up-regulated, while some antigenic protein expression levels were down-regulated. Above all, key molecules of DHA therapy were mainly involved in the parasites' rhoptry, transporter, antigenic variation, plasmodium exportin. These results offer us many hints to guide the further studies on mechanism of artemisinin and provide a new way for development of new antimalarial drugs.

Animals , Antimalarials , Artemisinins , Erythrocytes , Plasmodium falciparum , Transcriptome