Artemisinin-based antimalarial combination therapy amongst healthcare professionals in a tertiary facility in south-south Nigeria: preferences, tolerability, and cost considerations

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.

Recomendaciones para reumatólogos sobre el manejo farmacológico durante la emergencia sanitaria por COVID-19: opinión de un grupo de expertos / Recommendations for rheumatologists on pharmacological management during the COVID-19 health emergency: Expert group opinion

RESUMEN La enfermedad por Coronavirus 2019 (COVID-19) es una pandemia inesperada que ha pro vocado un estado de emergencia y que ha generado cambios drásticos en los protocolos de atención clínica. Para su tratamiento se ha descrito el papel de algunos medicamen tos usados habitualmente en artritis reumatoide, lupus eritematoso sistémico y otras enfermedades autoinmunitarias sistémicas. Debido a ello, existe un inminente riesgo de desabastecimiento, por lo cual el objetivo de esta revisión narrativa y opinión de expertos es formular recomendaciones generales clínicas y administrativas sobre el manejo de pacien tes ambulatorios con enfermedad autoinmunitaria o inflamatoria sistémica en el contexto de la pandemia por COVID-19.

ABSTRACT Coronavirus 2019 (COVID-19) is an unexpected pandemic that has caused a state of emergency, as well as generating drastic changes in clinical care protocols. Some drugs commonly used in rheumatoid arthritis, systemic lupus erythematosus, and other systemic autoimmune diseases have been described for its treatment. Therefore, there is an imminent risk of shortages. The aim of this narrative review and expert opinion is to present general recommendations on the clinical and administrative management of outpatients with autoimmune or systemic inflammatory disease, in the context of the COVID-19 pandemic.

Hearing of neonates without risk indicators for hearing loss and use of antimalarial drugs during pregnancy: a historical cohort study in the Northern Region of Brazil / Audição de neonatos sem indicadores de risco para perda auditiva e utilização de antimaláricos na gestação: um estudo de coorte histórica na Região Norte

Abstract Introduction: Studies have demonstrated the ototoxic effects of antimalarial drugs in individuals who receive these drugs, but little is known regarding the toxicity of these drugs in the newborn auditory system when administered to the mother receive the drug during pregnancy. Objective: To verify the incidence of hearing loss in neonates who have no other associated risk indicators, born to mothers treated for malaria during pregnancy. Methods: A retrospective, quantitative cohort study was developed at Hospital de Base Dr. Ary Pinheiro and Clínica Limiar, both located in the municipality of Porto Velho (Rondônia). The sample consisted of 527 newborns divided into two groups: exposed to antimalarials drugs during pregnancy group (n = 32) and non-exposed group (n = 495). Data collection took place from September 2014 to December 2015, through an interview with the mothers and/or guardians of the newborn, through the newborns' and the mothers' records, and the neonatal hearing screening database of the above-mentioned institutions. Results: All the neonates in the exposed group, assessed through the recording of transient otoacoustic emissions associated with the automated brainstem auditory evoked potential test, underwent neonatal hearing screening in the first examination. Among the newborns in the non-exposed group, 30 showed failure and were retested. Of these, one continued to fail and was referred for diagnosis, in whom the results showed to be within the normal range. Among the neonates of the exposed group, infection with Plasmodium vivax was the most frequent, and was similarly distributed among the gestational trimesters, and chloroquine was the most commonly used antimalarial drug treatment more often given during the third trimester; these findings did not show any influence on the audiological findings of the studied neonates. Conclusion: The present study did not identify any cases of hearing loss in neonates born to mothers who used antimalarial drugs during gestation.

Resumo Introdução: Estudos comprovam os efeitos ototóxicos dos antimaláricos em pessoas que fazem uso destes medicamentos, porém pouco se sabe sobre a toxicidade destes fármacos no sistema auditivo de neonatos quando ingeridos pelas mães no período gestacional. Objetivo: Verificar a incidência de perda auditiva em neonatos de mães tratadas para malária durante a gestação sem outros indicadores de risco associados. Método: Estudo quantitativo, de coorte retrospectivo, desenvolvido no Hospital de Base Dr. Ary Pinheiro e na Clínica Limiar, ambos em Porto Velho (Rondônia). Compuseram a amostra 527 recém-nascidos divididos em dois grupos: grupo exposto (n = 32) e grupo não exposto (n = 495). A coleta de dados ocorreu de setembro de 2014 a dezembro de 2015, através de entrevista com as genitoras e/ou responsáveis pelo recém-nascido, investigação nos prontuários dos neonatos e das genitoras e no banco de dados da triagem auditiva neonatal das instituições supracitadas. Resultados: Todos os neonatos do grupo exposto, avaliados através do registro das emissões otoacústicas transientes associado a realização do potencial evocado auditivo de tronco encefálico automático passaram na triagem auditiva neonatal no primeiro exame. Já, entre os recém-nascidos do grupo não exposto, 30 apresentaram falha e foram retestados. Destes, um continuou falhando e foi encaminhado para diagnóstico, no qual foram evidenciados resultados dentro da normalidade. Nos neonatos do grupo exposto, a infecção pelo Plasmodium vivax foi a mais frequente, mostrando distribuição semelhante entre os trimestres gestacionais, sendo a cloroquina o antimalárico mais utilizado e o tratamento medicamentoso realizado mais frequentemente no terceiro trimestre, porém tais achados não mostraram influência sobre os achados audiológicos dos neonatos estudados. Conclusão: O presente estudo não identificou casos de perda auditiva nos neonatos de mães que utilizaram antimaláricos na gestação.

Detection of antimalarial drug resistance polymorphisms in Plasmodium falciparum chloroquine resistance transporter and Plasmodium falciparum multidrug resistance 1 genes of Plasmodium falciparum found in Kano State, Nigeria

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.

Plasmodium vivax malaria across South America: management guidelines and their quality assessment

Abstract INTRODUCTION: Plasmodium vivax malaria represents a major public health problem. This study presents the quality assessment of clinical practice guidelines for the management of P. vivax malaria. METHODS: A systematic review was conducted in PubMed, SciELO, and Google Scholar. Additionally, five guidelines were assessed with the AGREE (Appraisal of Guidelines Research and Evaluation) II protocol. RESULTS The general performance on the domains of stakeholder involvement, development rigor, and editorial independence was low. CONCLUSIONS: Most guidelines lack a solid research methodology, which implies ambiguous accuracy. Much needs to be done in the area of therapeutics and quality of policies.

Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases

Abstract Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.(AU)

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.

Evaluation of toxic retinopathy caused by antimalarial medications with spectral domain optical coherence tomography / Avaliação da frequência de retinopatia por antimaláricos com o exame tomografia de coerência óptica de domínio espectral

ABSTRACT Purpose: To investigate the frequency of toxic retinopathy in patients with lupus erythematosus and rheumatoid arthritis with long-term use of chloroquine diphosphate or hydroxychloroquine through spectral domain optical coherence tomography and the outcomes of ophthalmological exams (visual acuity - Snellen's table, color vision test - Ishihara's table, fundoscopy, and retinography - red-free). Methods: A cross-sectional study was carried out involving the ophthalmologic evaluation of patients using regular chloroquine diphosphate or hydroxychloroquine for a period of 1 year or longer. The patients completed a questionnaire on their opinions and treatment regularity. The same patients underwent ophthalmologic examination and spectral domain optical coherence tomography. Results: The prevalence of toxic retinopathy caused by antimalarials was 4.15% (9 of 217 patients), 7.4% (4 of 54 patients) following chloroquine diphosphate usage, and 0.82% (1 of 121 patients) following hydroxychloroquine usage. Only patients with advanced stage maculopathy presented abnormalities during the ophthalmologic exam: the color vision test was altered in 11.1%, and visual acuity and fundoscopy were altered in 33.3%. Identification of early toxic retinopathy, detected in six patients, was possible using spectral domain optical coherence tomography. The mean duration of antimalarial drug usage among patients with toxic retinopathy was 10.4 years. Only 31% of the patients reported some symptoms during treatment, and although 24% were afraid to use the medication, they did so as prescribed. Conclusion: Use of spectral domain optical coherence tomography was essential for the diagnosis of early-stage antimalarial toxic retinopathy in patients with the following characteristics: asymptomatic, antimalarial use 7 days a week for a period of more than 5 years, and normal clinical ophthalmologic examination.

RESUMO Objetivo: Investigar a frequência da retinopatia tóxica em pacientes com lúpus eritematoso e artrite reumatóide com uso crônico de difosfato de cloroquina ou hidroxicloroquina, através de tomografia de coerência óptica de domínio espectral e os resultados dos exames oftalmológicos (acuidade visual - tabela de Snellen, teste de visão de cor - tabela de Ishihara, fundoscopia e retinografia - red free). Métodos: Foi realizado um estudo transversal envolvendo a avaliação oftalmológica de pacientes em uso regular de difosfato de cloroquina ou hidroxicloroquina por um período de um ano ou mais. Os pacientes responderam a um questionário sobre a sua opinião e regularidade do tratamento. Os mesmos pacientes realizaram exame oftalmológico clínico e tomografia de coerência óptica de domínio espectral. Resultados: A prevalência de retinopatia tóxica por antimaláricos foi de 4,15% (9 dos 217 pacientes), 7,4% (4 de 54 pacientes) após uso de difosfato de cloroquina e 0,82% (1 de 121 pacientes) após uso de hidroxicloroquina. Apenas os pacientes com maculopatia em fase avançada apresentaram alterações durante os exames clínicos: teste de visão de cores alterado em 11,1%, e a acuidade visual e fundoscopia foram alteradas em 33,3%. A identificação de retinopatia tóxica precoce, detectada em seis pacientes, foi possível por meio da tomografia de coerência óptica de domínio espectral. A duração média do tempo de uso de drogas antimaláricas entre os pacientes com retinopatia tóxica foi de 10,4 anos. Apenas 31% dos pacientes relataram algum sintoma durante o tratamento e apesar de 24% terem medo de usar a medicação, eles o fizeram conforme prescrito. Conclusão: O uso da tomografia de coerência óptica de domínio espectral foi essencial para o diagnóstico de retinopatia tóxica antimalárica em estágio inicial em pacientes com as seguintes características: uso assintomático, antimalárico 7 dias por semana por um período maior que cinco anos e exame oftalmológico clínico normal.

Alteraciones auditivas en artritis reumatoide, lupus eritematoso sistémico y síndrome de Sjögren / Hearing loss and rheumatoid arthritis, systemic lupus erythematosus and Sjögren 's syndrome

Resumen Introducción. En la actualidad no hay cifras sobre las personas que padecen artritis reumatoide (AR), lupus eritematoso sistémico (LES) o síndrome de Sjögren (SS) ni información sobre las alteraciones auditivas que puede causar el tratamiento farmacológico utilizado para controlar dichas enfermedades. Objetivo. Evidenciar las posibles afectaciones y alteraciones audiológicas y vestibulares producidas por AR, LES y SS o su tratamiento farmacológico. Materiales y métodos. Se analizaron los hallazgos clínicos de herramientas diagnósticas y procedimientos de prevención e intervención de alteraciones auditivas en artículos de investigación publicados en español, inglés, francés y portugués en bases de datos científicas entre los años 2000 y 2016. Resultados. Se extrajeron 62 artículos de investigación (31 de AR, 5 de LES, 12 de SS, 5 de Hipoacusia inmunomediada, 9 de medicamentos ototóxicos), 1 tesis doctoral sobre AR, 1 tesis doctoral sobre AR y LES y 1 guía de práctica clínica para la detección temprana, diagnóstico y tratamiento de AR. Se evidenció que las pérdidas auditivas con mayor reporte son hipoacusia neurosensorial, lesiones en cadena osicular y vestíbulo-coclear. Conclusiones. Se confirmó la relación entre las lesiones audiológicas y AR, LES y SS, pero aun no es claro el desarrollo de los ototóxicos.

Abstract Introduction: Currently, figures on people suffering from rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or Sjögren's syndrome (SS) are not available, as well as information on auditory alterations caused by the pharmacological treatment used to control said diseases. Objective: To demonstrate possible hearing and vestibular disorders caused by RA, SLE and SS or their pharmacological treatment. Materials and methods: Clinical findings of diagnostic tools and prevention and intervention procedures for hearing disorders found in research articles published in Spanish, English, French and Portuguese in scientific databases between 2000 and 2016 were analyzed. Results: 62 research papers were obtained (31 on RA, 5 on SLE, 12 on SS, 5 on immune-mediated hearing loss, and 9 on ototoxic drugs), a doctoral thesis on RA, a doctoral thesis on RA and LES and a clinical practice guideline for the early detection, diagnosis and treatment of RA. The most frequent types of hearing loss reported are sensorineural hearing loss, ossicular chain lesions and vestibular-cochlear disorders. Conclusions: The relationship between hearing lesions and RA, LES and SS was confirmed, but the development of ototoxic drugs is not clear yet.

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

Prescripción de antipalúdicos en hospitales centrales y provinciales de Angola / Antimalarials prescription in central and provincial hospitals in Angola

Introducción: La malaria constituye la primera causa de morbilidad y mortalidad en Angola y se desconocen las características de la prescripción de antipalúdicos en los hospitales. Objetivo: Caracterizar la prescripción de antipalúdicos en pacientes internados en hospitales centrales y provinciales de Angola. Método: Estudio de Utilización de Medicamentos, tipo indicación-prescripción, con elementos de esquema terapéutico. La muestra fue de 2 634 pacientes. La variable principal: evaluación de la prescripción, se operacionalizó como adecuada o no en función de la indicación, pauta terapéutica y contraindicaciones. Resultados: Predominó la malaria complicada (66,6 por ciento) y el sexo femenino en niños (51,7 por ciento) y adultos (51,0 por ciento). Se indicaron 4 518 prescripciones. La quinina endovenosa (20,4 por ciento) fue el tratamiento más utilizado en la malaria complicada y la quinina tabletas (26,5 por ciento) en la malaria simple. El 94,8 por ciento de las prescripciones no presentaron contraindicaciones, mientras que el 69,0 por ciento fueron adecuadas en su selección y el 65,1 por ciento en la pauta terapéutica. La evaluación de la prescripción resultó ser adecuada (55,0 por ciento). La malaria complicada presentó mayor número de prescripciones no adecuadas (47,5 por ciento). Conclusiones: Existe prescripción irracional de antipalúdicos, con mayor repercusión en la malaria complicada. Persiste una baja utilización de derivados de la artemisina, por lo que se incumple lo establecido en la Guía de Tratamiento de la Malaria(AU)

Introduction: The characteristics of the prescription of antimalarials in hospitals, where malaria is the first cause of mortality and morbidity, are unknown. Objective: To characterize the prescription of antimalarials in patients admitted to central and provincial hospitals in Angola. Methods: A Study of Drug's Use was made, type indication-prescription, with elements of a therapeutic scheme. The sample was of 2 634 patients. The main variable (evaluation of the prescription) was operationalized in adequate or not according to the indication, therapeutic guideline and contraindications. Absolute frequency and percentage were used as summary measures. Results: The most represented patients were adults (54.1 percent) and those admitted in general hospitals (82.6 percent). Complicated malaria was predominant (66.6 percent) and female sex in children (51.7 percent) and adults (51.0 percent). There were 4 518 prescriptions. Intravenous quinine (20.4 percent) was the most used treatment in complicated malaria and quinine tablets (26.5 percent) in simple malaria. 94.8 percent of the prescriptions had no contraindications, while 69.0 percent were adequate in their selection and 65.1 percent in the therapeutic regimen. The evaluation of the prescription was adequate (55.0 percent). Complicated malaria had a greater number of inappropriate prescriptions (47.5 percent). Conclusions: The existence of irrational prescription of antimalarials is evidenced with more repercussion in complicated malaria. There is still a low use of artemisinin derivatives, in breach of the Guide for Malaria's Treatment(AU)

Qualidade de vida em tratamento de lúpus eritematoso sistêmico com antimaláricos / Quality of life in treatment of systemic lupus erythematosus with antimalarials

OBJETIVO: Avaliar se o bem-estar global de pacientes com lúpus eritematoso sistêmico é afetado pelo uso de antimaláricos. MÉTODOS: Estudo transversal observacional analítico, realizado com 118 indivíduos do sexo feminino, sendo que 51 faziam uso de antimaláricos por, no mínimo, 2 anos (Grupo 1), 17 não utilizavam esse método terapêutico (Grupo 2) e 50 não tinham lúpus eritematoso sistêmico (Grupo 3). Dados epidemiológicos, clínicos e sorológicos das pacientes lúpicas foram obtidos por meio da análise de prontuários médicos, e a qualidade de vida foi avaliada pelo questionário Medical Outcomes Study Short-Form Health Survey version 2 (SF-12v2). RESULTADOS: O uso de antimaláricos foi associado à menor ocorrência de psicose e lesões renais, apesar de levar a uma frequência maior de convulsões. Quanto à percepção individual da qualidade de vida, não houve diferença significativa entre os três grupos. Porém, quando considerado o tabagismo entre as usuárias de antimaláricos, o SF-12v2 de saúde mental de fumantes foi menor do que de não fumantes. CONCLUSÃO: Pacientes lúpicas em uso de antimaláricos tiveram menor incidência de psicose e glomerulonefrite, mas não houve diferença significativa em relação à qualidade de vida e ao uso de antimaláricos, com exceção de fumantes em uso da medicação, que tiveram escore do SF-12v2 de saúde mental menor do que não fumantes em uso da mesma medicação.(AU)

OBJECTIVE: To evaluate whether global quality of life of Systemic Lupus Erythematosus patients is affected by the use of antimalarials. METHODS: This is an observational, analytical cross-sectional study carried out with 118 female individuals, of whom 51 have been on antimalarials for at least 2 years (group 1), 17 were not using this therapy (group 2), and 50 did not have Systemic Lupus Erythematosus (group 3). Epidemiological, clinical and serological data of Systemic Lupus Erythematosus patients were obtained through the review of medical records, and quality of life was assessed using the SF-12 questionnaire. RESULTS: Antimalarial use was associated with a lower occurrence of psychosis and renal lesions, although it led to a higher prevalence of seizures. Regarding the individual perception of quality of life, there was no significant difference among the 3 groups. However, when smoking habits were considered among antimalarial users, mental health score in the SF-12 was lower in smokers than in non-smokers. CONCLUSION: Systemic Lupus Erythematosus female patients using antimalarials had a lower incidence of psychosis and glomerulonephritis, but no significant differences were found regarding antimalarial use and quality of life, except for the group of smokers using antimalarials, who had lower mental scores in the SF-12 than non-smokers using the same medication.(AU)

Reacciones adversas por antipalúdicos en hospitales centrales y provinciales de Angola / Adverse reactions due to antimalarials in central and provincial hospitals in Angola

Introducción: El paludismo es la primera causa de morbilidad y mortalidad en Angola. Las particularidades de las reacciones adversas a antipalúdicos no están bien establecidas en pacientes hospitalizados. Objetivo: Caracterizar las reacciones adversas a medicamentos antipalúdicos. Método: Estudio de farmacovigilancia activa de serie de casos. El universo fueron 2 634 pacientes ingresados con paludismo confirmado en los hospitales centrales y provinciales de Angola durante el primer semestre de 2015. Médicos entrenados realizaron pesquisa diaria a través de interrogatorios farmacológicos, pases de visita y revisión de historias clínicas. Resultados: Hubo una tasa de 7,5 reacciones adversas por cada 100 pacientes internados. El 77,8 por ciento eran adultos y el 15,7 por ciento niños. Hubo predominio del sexo femenino en los niños y adultos (51,6 por ciento y 52,6 por ciento, respectivamente). Las reacciones más notificadas fueron las náuseas y vómitos (14,3 por ciento), el dolor abdominal (13,4 por ciento) y la erupción cutánea y los temblores, ambos con el 11,7 por ciento. La quinina endovenosa fue el antipalúdico de mayores reportes de reacciones adversas (29,0 por ciento). Además, las quininas (oral y endovenosa) provocaron el 41,1 por ciento del total de reacciones adversas encontradas. Predominaron las reacciones adversas leves (73,2 por ciento), las probables (47,6 por ciento) y las de aparición frecuentes (69,7 por ciento). Conclusiones: Existen reacciones adversas a los tratamientos antipalúdicos impuestos en los hospitales centrales y provinciales de Angola. Es importante la vigilancia activa en la identificación y el reporte de los efectos adversos por fármacos en los escenarios con sistema de farmacovigilancia que no alcanzan una implementación efectiva(AU)

Introduction: Malaria is the main cause of morbidity and mortality in Angola. Characteristics of adverse reactions due to antimalarials are not well established in hospitalized patients. Objective: Characterization of adverse reactions to antimalarial drugs. Method: An active pharmacovigilance study was carried out in a series of cases. There was a total of 2 634 patients admitted in central and provincial hospitals of Angola with confirmed malaria during the first semester of 2015. Trained doctors conducted daily screenings through pharmacological questionnaires, visits to the patients and reviews of medical records. Results: It was found that there was a rate of 7.5 adverse reactions per 100 hospitalized patients. 77.8 percent were adults and 15.7 percent were children. There was a predominance of females in children and adults (51.6 percent and 52.6 percent, respectively). The most commonly reported reactions were nausea and vomiting (14.3 percent), abdominal pain (13.4 percent) and rash and tremors both with 11.7 percent. Intravenous quinine was the antimalarial with the highest number of reports of adverse reactions (29.0 percent). In addition, oral and intravenous quinine caused 41.1 percent of the total number of ADRs found. Mild adverse reactions (73.2 percent), probable adverse reactions (47.6 percent) and frequent adverse reactions (69.7 percent) were predominant. Conclusions: Data provided by the study show the existence of adverse reactions to antimalarial treatments in central and provincial hospitals in Angola. It is highlighted the importance of an active surveillance in the identification and reporting of adverse effects due to drugs in scenarios with a pharmacovigilance system that does not reach an effective implementation(AU)

Research progress on heme metabolism in intraerythrocytic plasmodium / 中国中药杂志

Heme is a key metabolic factor in all life. Malaria parasite has de novo heme-biosynthetic pathway, however the growth and development of parasite depend on the hemoglobin-derived heme metabolism process during the intraerythrocytic stages, such as the ingestion and degradation of hemoglobin in the food vacuole. The hemoglobin metabolism in the food vesicles mainly includes four aspects: hemoglobin transport and intake, hemoglobin enzymolysis to produce heme, heme polymerization into malarial pigment, and heme transport via the food vacuole. The potential mechanisms of antimalarial drugs,such as chloroquine, artemisinin and atovaquone may be related to this process. The main four aspects of this metabolic process, key metabolic enzymes, effects of antimalarial drugs on the process and their potential mechanism of action would be summarized in this paper, providing ideas for rational use and mechanism exploration of similar drugs.

Lupus tumidus: a report of two cases

Abstract Lupus tumidus is considered a rare subtype of chronic cutaneous lupus erythematosus, characterized by erythema and bright urticarial erythematous-violaceous lesions that leave no scars after regression. Histopathology reveals perivascular and periannexal lymphohistiocytic infiltrates in the papillary and reticular dermis and interstitial mucin deposition. Treatment is based on photoprotection, topical corticosteroids and antimalarials. We report two cases of lupus tumidus, which deserve attention for their low frequency in the literature, in addition to their relevance as a differential diagnosis among dermatologic disorders.

Antipalúdicos en dermatología / Antimalarials in dermatology

Se realiza una breve revisión de los usos de los antipalúdicos en el lupus eritematoso y en otras condiciones dermatológicas, haciendo hincapié en la importancia de respetar la dosis máxima recomendada por día, la que variará de acuerdo con el peso ideal del paciente, medido por el Índice de Masa Corporal.

This article highlights the different antimalarials used within dermatology through their pharmacologic properties and mechanism of action, as well as indicating their clinical uses. In addition, contraindications adverse effects, and possible drug interactions of antimalarials are reviewed. The controversial among different countries about dosage and retinal damage are discussed.

Adaptación y optimización de un método de lectura por fluorometría en el modelo farmacológico in vitro de cultivo de Plasmodium falciparum / Adaptation and optimization of a fluorometric reading method, in the in vitro pharmacological model of Plasmodium falciparum culture

El modelo farmacológico de cultivo in vitro de P. falciparum es crucial en el tamizaje inicial de sustancias o extractos de plantas con posible actividad antiplasmodial. La densidad parasitaria puede determinarse mediante variadas metodologías, sin embargo, se han descrito numerosas ventajas y desventajas asociadas a cada una de ellas. Se evaluaron el tiempo de incubación necesario para la tinción y el uso de cultivos asincrónicos o sincrónicos en busca de valores óptimos; evidenciando un tiempo óptimo de 2 h, y límites de detección y cuantificación, menores en cultivos asincrónicos. Empleando las cepas FCR3 y FCB2 se evidenció un ruido de fondo de 12% y 38% respectivamente; la linealidad mostró una buena correlación, r² de 0,9644 (FCR3) y 0,9841 (FCB2) y una pendiente de 1761,8 y 852,4 respectivamente. Además, se comprobó había concordancia entre los métodos, fluorométrico con SYBR Green I (SYBRG I) y microscópico con Giemsa, con diferencia media de 0,00002% y 0,09109% para FCR3 y FCB2 respectivamente. Los límites de detección y cuantificación fueron 0,5% y 1,5% de parasitemia. El factor Z con FCB2 fue 0,376, en tanto que con FCR3 alcanzó 0,702. La concentración inhibitoria 50 (CI50) frente a P. falciparum FCR3, generada por cloroquina (CQ) fue 0,37 mcg/mL por microscopía y 0,35 mcg/mL por fluorometría. Nuestros hallazgos sugieren que el ensayo de fluorescencia con SYBRG I, empleando fluorómetros comúnmente disponibles en muchos laboratorios, es preciso, robusto, rápido y exacto; para la evaluación in vitro de sustancias o extractos con posible actividad antiplasmodial.

The in vitro pharmacological model of P. falciparum culture is crucial in the initial screening for substances or plant extracts with possible antiplasmodial activity. The parasite density can be determined by varied methods, however have been described numerous advantages and disadvantages associated with each of them. The incubation time required for staining and the use of synchronous or asynchronous cultures were assessed for optimal settings; showing optimal time of 2 h, and lower limits of detection and quantification in asynchronous cultures. Employing the FCB2 and FCR3 strains, was evidenced a background noise of 12% and 38% respectively; linearity showed a good correlation, r² of 0.9644 (FCR3) and 0.9841 (FCB2) and a slope of 1761.8 and 852.4, respectively. It was evidenced agreement between the methods, fluorometric with SYBR Green I (SYBRG I) and microscopic with Giemsa, the mean difference was 0.00002% and 0.09109% respectively for FCR3 and FCB2, The limits of detection and quantification were 0.5% and 1.5% of parasitaemia. The Z factor was 0.376 with FCB2, whereas with FCR3 reached 0.702. The inhibitory concentration 50 (IC50) against P. falciparum FCR3, generated by chloroquine (CQ), was 0.37 mcg/mL by microscopy and 0.35 mcg/mL by fluorometry. Our findings suggest that the SYBRG I fluorescence based assay, by using fluorometers commonly available in many laboratories, is precise, robust, fast and accurate; for the in vitro evaluation of substances or extracts with possible antiplasmodial activity.

Diagnosis and scr eening for antimalarial retinopathy：two cases report and literature review / 中华风湿病学杂志

Objective To analyze antimalarial assosiated retinopathy detected by different methods with of modern ocular fundus examination, and explore screening strategy and the diagnosis of hydroxych-loroquine assosiatedretinopathy according to clinical experience and international guidelines. Methods Full fundus examination was performed in two patients with antimalarial retinopathy. The related literature were reviewed. Results Two patients had bull's eyes maculopathy and abnormal visual fields. Conclusion Clin-icians' alertness to hydroxychloroquine related retinopathy may improve early diagnosis of hydroxychloroquine toxicity. New objective tests are more sensitive than visual fields examination. Visible bull's-eye maculopathy is a late change, and the goal of screening is to recognize toxicity at early stage.

Artemisinin anti-malarial drugs in China

Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti-malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970s, a special period in China, by hundreds of scientists all together under the "whole nation" system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements.

Aspidosperma (Apocynaceae) plant cytotoxicity and activity towards malaria parasites. Part II: experimental studies withAspidosperma ramiflorum in vivo and in vitro

Several species of Aspidospermaplants are used to treat diseases in the tropics, including Aspidosperma ramiflorum, which acts against leishmaniasis, an activity that is experimentally confirmed. The species, known as guatambu-yellow, yellowperoba, coffee-peroba andmatiambu, grows in the Atlantic Forest of Brazil in the South to the Southeast regions. Through a guided biofractionation of A. ramiflorumextracts, the plant activity against Plasmodium falciparumwas evaluated in vitro for toxicity towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human monocytes isolated from peripheral blood. Six of the seven extracts tested were active at low doses (half-maximal drug inhibitory concentration < 3.8 µg/mL); the aqueous extract was inactive. Overall, the plant extracts and the purified compounds displayed low toxicity in vitro. A nonsoluble extract fraction and one purified alkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56 and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). The structure, activity and low toxicity of isositsirikine in vitro are described here for the first time in A. ramiflorum, but only the neutral and precipitate plant fractions were tested for activity, which caused up to 53% parasitaemia inhibition of Plasmodium bergheiin mice with blood-induced malaria. This plant species is likely to be useful in the further development of an antimalarial drug, but its pharmacological evaluation is still required.