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.

Electrocardiographic effect of artemisinin-piperaquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine treatment in falciparum malaria patients

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.

Primum non nocere - Are chloroquine and hydroxychloroquine safe prophylactic/treatment options for SARS-CoV-2 (covid-19)?

ABSTRACT Chloroquine (CQ) and its analog hydroxychloroquine (HCQ) were recently included in several clinical trials as potential prophylactic and therapeutic options for SARS-COV-2 infection/covid-19. However, drug effectiveness in preventing, treating, or slowing the progression of the disease is still unknown. Despite some initial promising in vitro results, rigorous pre-clinical animal studies and randomized clinical trials have not been performed yet. On the other hand, while the potential effectiveness of CQ/HCQ is, at best, hypothetical, their side effects are factual and most worrisome, particularly when considering vulnerable groups of patients being treated with these drugs. in this comment, we briefly explain the possible mechanisms of action of CQ/HCQ for treating other diseases, possible actions against covid-19, and their potent side effects, in order to reinforce the necessity of evaluating the benefit-risk balance when widely prescribing these drugs for SARS-COV-2 infection/covid-19. We conclude by strongly recommending against their indiscriminate use.

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.

Effect of artemisinin-piperaquine treatment on the electrocardiogram of malaria patients

Abstract INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria. METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study. RESULTS: Some cases of QT prolongation were observed. However, no TdP was found. CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.

Therapeutic failure after regimen with artemether-lumefantrine combination therapy: a report of three cases in Benin City, Nigeria

Abstract Artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated malaria. Currently, there appears to be a downward trend in the efficacy of ACT in some parts of sub-Saharan Africa because some patients have been positive for Plasmodium parasite 3 days after artemether-lumefantrine treatment. We reported three cases of possible parasite resistance to artemether-lumefantrine therapy. All subjects had complete parasite clearance when treated with other antimalarial drugs. This observation necessitates the urgent need to re-evaluate artemether-lumefantrine medication in Nigeria since it is one of the most commonly used ACT drug.

Glucose-6-phosphate dehydrogenase deficiency and the use of primaquine: top-down and bottom-up estimation of professional costs / Deficiência de glicose-6-fosfato desidrogenase e uso de primaquina: estimativa de custos de profissionais por macrocusteio e microcusteio

ABSTRACT The aim of this study has been to study whether the top-down method, based on the average value identified in the Brazilian Hospitalization System (SIH/SUS), is a good estimator of the cost of health professionals per patient, using the bottom-up method for comparison. The study has been developed from the context of hospital care offered to the patient carrier of glucose-6-phosphate dehydrogenase (G6PD) deficiency with severe adverse effect because of the use of primaquine, in the Brazilian Amazon. The top-down method based on the spending with SIH/SUS professional services, as a proxy for this cost, corresponded to R$60.71, and the bottom-up, based on the salaries of the physician (R$30.43), nurse (R$16.33), and nursing technician (R$5.93), estimated a total cost of R$52.68. The difference was only R$8.03, which shows that the amounts paid by the Hospital Inpatient Authorization (AIH) are estimates close to those obtained by the bottom-up technique for the professionals directly involved in the care.

RESUMO A pesquisa teve por objetivo estudar se o macrocusteio, baseado no valor médio identificado no Sistema de Internação Hospitalar (SIH/SUS), constitui um bom estimador do custo de profissionais de saúde por paciente, tendo como comparação o método de microcusteio. O estudo foi desenvolvido no contexto da assistência hospitalar oferecida ao portador da deficiência de glicose-6-fosfato desidrogenase (dG6PD) do sexo masculino com evento adverso grave devido ao uso da primaquina, na Amazônia Brasileira. O macrocusteio baseado no gasto em serviços profissionais do SIH/SUS, como proxy desse custo, correspondeu a R$60,71, e o microcusteio, baseado nos salários do médico (R$30,43), do enfermeiro (R$16,33) e do técnico de enfermagem (R$5,93), estimou um custo total de R$52,68. A diferença foi de apenas R$8,03, mostrando que os valores pagos pela Autorização de Internação Hospitalar (AIH) são estimadores próximos daqueles obtidos por técnica de microcusteio para os profissionais envolvidos diretamente no cuidado.

Metahemoglobinemia adquirida inducida por fármacos antipalúdicos / Acquired methemoglobinemia induced by antymalaric drugs

Clásicamente se describe cianosis como niveles de hemoglobina desoxigenada en sangre periférica por encima de 5g/dl; sin embargo se ha dejado a un lado, que dicha expresión clínica no sólo responde a esta condición, sino también a la acumulación distal de pigmentos anómalos producto de la alteración en la morfología habitual de la molécula de hemglobina o el estado químico de ésta. Por tal motivo, se presenta un interesante caso clínico en paciente masculino de 35 años de edad, quien consulta por cuadro febril agudo y diagnóstico de Paludismo por Plasmodium vivax, iniciando tratamiento antipalúdico. Posteriormente presenta, en ausencia de fiebre, cianosis peribucal y acral acompañada de disminución de la saturación a 83% por oximetría de pulso. El diagnóstico se basó en la evidencia clínica y la oximetría de pulso, el manejo terapéutico consistió en la administración de oxígeno húmedo y bolos de azul de metileno, notando franca mejoría clínica(AU)

Methemoglobinemia has traditionally been described in multiple studies. Cyanosis, and deoxygenated hemoglobin levels in peripheral blood above 5g / dL, not only responds to this condition, but also to the distal accumulation of anomalous pigments as products of an alteration in the normal morphology of the haemoglobin molecule or chemical state of this. An interesting case report is presented in a male, who after the diagnosis of Plasmodium Vivax Malaria and malaria treatment presenteded perioral the and distal cyanosis, as well as desaturation of 83% by oximetry. The diagnosis was based on clinical evidence and pulse oximetry, and therapeutic approach was based on the administration of wet oxygen and methylene blue bowling, showing marked clinical improvement(AU)

Slow clearance of Plasmodium vivax with chloroquine amongst children younger than six months of age in the Brazilian Amazon

Plasmodium vivax is the most widespread parasite causing malaria, being especially prevalent in the Americas and Southeast Asia. Children are one of the most affected populations, especially in highly endemic areas. However, there are few studies evaluating the therapeutic response of infants with vivax malaria. This study retrospectively evaluated the parasitaemia clearance in children diagnosed with vivax malaria during the first five days of exclusive treatment with chloroquine (CQ). Infants aged less than six months old had a significantly slower parasitaemia clearance time compared to the group of infants and children between six months and 12 years old (Kaplan-Meier survival analysis; Wilcoxon test; p = 0.004). The impaired clearance of parasitaemia in younger children with vivax malaria is shown for the first time in Latin America. It is speculated that CQ pharmacokinetics in young children with vivax malaria is distinct, but this specific population may also allow the detection of CQ-resistant parasites during follow-up, due to the lack of previous immunity. .

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

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

Drugs use during pregnancy at Medani Maternity Hospital, Sudan

There is a limited knowledge on use of drugs during pregnancy including beneficial and possible adverse effects of drugs on both the mother and the fetus. To investigate epidemiology of use of drugs during pregnancy. A cross sectional hospital based study at Medani Hospital during the period December 2011. After signing an informed consent, a pre-tested questionnaire was used to gather data from each parturient mother on her age, parity, level of education, antenatal care visits and use of drug during the index pregnancy. The vast majority [334; 98.2%] of the interviewed women used drugs during the index pregnancy. Around ten percent [35; 10.5%] of these women used the drugs in the first trimester of pregnancy. The majority [266; 78.2%] used the drugs in third trimester and the rest used it in the second trimester. The most common drugs used were antibiotics, tonics, antimalarials and antiemetic. There is a very high rate of drug use in this setting. Antibiotics and antimalarials drugs were the most used drugs

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.

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

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

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

Complicações oculares da terapêutica com a cloroquina e derivados / Ocular complications of chloroquine and derivatives therapy

INTRODUÇÃO: Os derivados das 4-aminoquinolonas vêm sendo utilizados desde sua industrialização na terapêutica da malária, das doenças reumatológicas e dermatológicas. Essas drogas apresentam reações adversas sistêmicas e oculares. As reações adversas sistêmicas afetam o sistema gastrointestinal, sistema nervoso, sistema muscular esquelético e a pele, e as oculares são: fotofobia, córnea verticilata, poliose, catarata, paralisia dos músculos extraoculares, uveíte anterior, maculopatia tóxica, neurite óptica. OBJETIVO: Revisão bibliográfica das complicações do uso de cloroquina e derivados. Analisar evolução e estágio atual da propedêutica. Sugerir conduta prática no mapeamento precoce dos sinais de toxicidade. MÉTODOS: Revisão bibliográfica através da pesquisa no banco de dados MEDLINE, PUBMED, LILACS e SciELO. DISCUSSÃO: São descritos todos os exames que podem ser utilizados para mapeamento das reações adversas oculares, tais quais: exame oftalmológico completo, com ênfase na biomicroscopia e oftalmoscopia binocular indireta, campo visual computadorizado, tela de Amsler, visão de cores, exames eletrofisiológicos, polarimetria e tomografia de coerência óptica. É feita a descrição do quadro de maculopatia enfocando epidemiologia, fatores de risco, histopatologia e propedêutica. É descrita a estrutura química e as diferenças entre os derivados das 4-aminoquinolonas. CONCLUSÃO: Todo paciente em uso de cloroquina e seus derivados devem ser acompanhados e documentados desde seu início e até atingir a dose cumulativa acima de 100 gramas. Quanto maior a dose cumulativa, maior deve ser a nossa preocupação com o seguimento desse paciente.

INTRODUCTION: Byproducts of 4-aminoquinolones are being used since its industrialization in the treatment of malaria, rheumatic and dermatologic diseases. These drugs present systemic and ocular adverse events. Systemic adverse reactions affect the gastrointestinal, nervous and skeletal muscular systems and the skin. Ocular adverse reactions are: photophobia, cornea verticillata, poliosis, cataract, extraocular muscle palsy, anterior uveitis, toxic maculopathy and optical neuritis. PURPOSE: Bibliography review of complications due to the use of chloroquine and its derivatives. To analyze the current practice and propedeutics' evolution. To suggest practical managements for early toxicity signs. METHODS: Bibliographic review through research on MEDLINE, PUBMED, LILACS and SciELO database. DISCUSSION: All exams that can be used to screen ocular adverse reactions are described, such as: complete ophthalmologic exam, with emphasis on biomicroscopy and indirect binocular ophthalmoscopy, computerized visual field, Amsler grid testing and color vision testing, electrophysiological exams, polarimetry and optical coherence tomography. A description of maculopathy is presented, focusing on epidemiology, risk factors, histopathology and propedeutics. Chemical structure and the differences between 4-aminoquinolone derivatives are described. CONCLUSION: All patients using chloroquine and its derivatives must be followed-up and documented since the beginning of the therapy until they reach a cumulative dose above 100 grams. The higher the cumulative dose, the more we must be concerned with patient follow-up.

Clinical aspects of hemolysis in patients with P. vivax malaria treated with primaquine, in the Brazilian Amazon

This report describes the development of hemolysis in eighteen glucose-6-phosphate dehydrogenase deficient patients treated for Plasmodium vivax malaria with chloroquine and primaquine. The most frequent findings accompanying hemolysis were fever and leukocytosis, in addition to anemia requiring red blood cell transfusion, and development of acute renal failure. Hemolysis in patients using primaquine is not infrequent and contributes to the morbidity of infection caused by Plasmodium vivax.

Tomografia de coerência óptica na avaliação da camada de fibras nervosas peripapilar nos usuários de cloroquina / Optical coherence tomography to evaluate peripapillary retinal nerve fiber layer in chloroquine patients

OBJETIVO: Analisar a camada de fibras nervosas nos usuários de cloroquina com a tomografia de coerência óptica (OCT). MÉTODOS: A espessura da camada de fibras nervosas foi mensurada pelo Stratus OCT® através do protocolo scan rápido da camada de fibras nervosas em 94 olhos de 48 pacientes usuários de cloroquina a pelo menos um ano e sem alteração macular aparente. A dose cumulativa e dose diária máxima (mg/kg/dia) e o tempo de uso da cloroquina foram correlacionadas com a espessura da camada de fibras nervosas. Os dados formam comparados com um grupo controle de 30 pacientes não usuários de cloroquina. Todos os pacientes foram submetidos a um exame oftalmológico completo incluindo medida da acuidade visual, refração, pressão intraocular, fundoscopia, retinografia e medida da escavação de papila. RESULTADOS: Comparação entre a média da espessura da camada de fibras nervosas entre usuários do antimalárico (107,60 ± 13,25 µm) e o grupo controle (99,05 ± 13,08 µm) teve uma associação estatisticamente significativa (p=0,0137). Também foi encontrada essa associação entre os quadrantes temporal, superior e inferior da camada de fibras nervosas peripapilar dos dois grupos. Ao analisar a camada de fibras nervosas através das 12 h do relógio detectou-se pelo menos um defeito focal em mais de 50 por cento dos usuários da medicação. Nos pacientes com o defeito focal foi observado uma relação com a dose diária máxima (p=0,0120). CONCLUSÃO: A tomografia de coerência óptica demonstrouse eficaz na detecção da diminuição da camada de fibras nervosas em usuários de cloroquina sem alterações fundoscópicas aparentes. Dessa forma, a tomografia de coerência óptica pode contribuir para o diagnóstico mais precoce da retinopatia por cloroquina.

PURPOSE: To evaluated the retinal nerve fiber layer in chloroquine patients with optical coherence tomography (OCT). METHODS: Nerve fibers layer thickness was measured by a proprietary OCT Stratus® through the fast retinal nerve fiber layer protocol in ninety-four eyes of 48 patients exposed to chloroquine for at least one year with no apparent macular disorder. Cumulative dose, maximum daily dose (mg/kg/day) and time of chloroquine use were correlated with the retinal nerve fiber layer thickness. Data were compared with a control group of 30 patients who did not use chloroquine. All patients underwent a complete ophthalmologic examination including visual acuity, refraction, intraocular pressure, fundoscopy, angiography and measurement of cup-to-disc ratio. RESULTS: The average thickness of retinal nerve fiber layer between antimalaric users (107.60 ± 13.25 µm) and the control group (99.05 ± 13.08 µm) had a statistically significant difference (p=0.0137). Furthermore, a positive association of the peripapillary thickness measurements between temporal, upper and lower quadrants of both groups was found. Twelve clock hours retinal nerve fiber layer analysis detected at least one focal defect in more than 50 percent of the medication users. Particularly, a statistical correlation with the maximum daily dose was found in patients with focal defects (p=0.0120). CONCLUSION: Optical coherence tomography is effective in detecting nerve fiber layer loss in chloroquine patients without apparent fundus changes. Thus, optical coherence tomography may contribute to the early diagnosis of chloroquine retinopathy.

Maculopatia tóxica por antimaláricos: detecção pela tomografia óptica espectral de alta resolução: relato de casos / Toxic maculopathy caused by antimalarial drugs: detection using spectral domain OCT: case reports

As drogas antimaláricas, como a cloroquina, são úteis no controle de doenças reumáticas, mas podem causar lesões oculares potencialmente graves como a retinopatia cloroquínica (RC). Neste relato, são descritos os achados à tomografia de coerência óptica convencional e na espectral de alta resolução (HD-OCT) em aparelho CirrusTM HD-OCT de duas pacientes com RC. Em um dos casos, chama a atenção à similaridade entre a imagem de atrofia do epitélio pigmentado retiniano (EPR) na angiofluoresceinografia e a obtida na HD-OCT por segmentação "en -face" (reconstruções coronais). Em outra paciente, com sinais clínicos de maculopatia, mas sem anormalidades na angiofluoresceinografia, os sinais de atrofia do EPR foram também observados nos "scans" da HD-OCT, levantando a possibilidade de que esta técnica possa permitir a detecção precoce desta doença.

Antimalarial drugs, such as chloroquine, are useful in the management of rheumatic diseases, but may cause a potentially blinding condition known as toxic maculopathy. This report describes the findings on standard and on high-resolution spectral domain ocular coherence tomography performed in a CirrusTM HD-OCTdevice in two patients with chloroquine maculopathy. In one case, a very similar aspect of retinal pigment epithelium (RPE) plaque atrophy occured in both angiographic and HD-OCT images obtained by "en-face" (coronal) segmentation. In another patient with clinical signs of maculopathy and no angiographic abnormalities, signs of RPE atrophy could also be observed in HD-OCT scans, raising the possibility that this technique may allow the early detection of the disease.

Métodos diagnósticos para retinopatia induzida pelo difosfato de cloroquina nos portadores de lúpus eritematoso sistêmico / Diagnostic methods for chloroquine diphosphate induced retinopathy in systemic lupus erythematosus

OBJETIVOS: Avaliar diferentes métodos diagnósticos para a avaliação de pacientes portadores de lúpus eritematoso sistêmico, usuários crônicos do difosfato de cloroquina (DFC) e, portanto, com alto risco para retinopatia tóxica. MÉTODOS: Foram analisados 72 olhos de 36 pacientes consecutivos, seguidos no Serviço de Reumatologia do Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, de julho de 2007 a abril de 2008. Dados demográficos e clínicos foram avaliados com o intuito de estudar os fatores de alto risco e comparar os seguintes métodos oftalmológicos: acuidade visual, biomicroscopia da córnea, biomicroscopia do fundo, retinografia, angiofluoresceinografia da retina, campo visual macular com mira branca. RESULTADOS: Dos 36 pacientes, 34 (94,4 por cento) eram mulheres. A média de idade foi 39,9 ± 9,8 anos, com tempo de doença igual a 13,9 ± 6,6 anos. Além do uso crônico da cloroquina, os pacientes apresentaram altas doses diárias (>3 mg/kg) e cumulativas. Não foi observada relação entre estes fatores de alto risco e maior prevalência de retinopatia. Foi encontrada prevalência de retinopatia igual a 38,9 por cento, confirmada por alterações bilaterais, centrais ou paracentrais e reprodutíveis no exame de campo visual. Outros exames indicados para seguimento, como acuidade visual, biomicroscopia de fundo e angiofluoresceinografia não foram capazes de diagnosticar a maioria das alterações confirmadas pelo campo visual. CONCLUSÃO: Foi observada alta prevalência de retinopatia por cloroquina entre os pacientes com alto risco, usuários crônicos do DFC, segundo os achados do campo visual. A avaliação desses pacientes deve considerar a realização do exame de campo visual em intervalos menores que os propostos, mesmo quando não há suspeita clínica.

PURPOSE: To evaluate different diagnostic methods for high risk chloroquine retinopathy due to prolonged use of chloroquine (more than 5 years) by systemic lupus erythematosus patients. Methods: Seventy-two eyes of 36 consecutive patients, followed in the Division of Rheumatology, School of Medicine, University of São Paulo, were analyzed from July 2007 to April 2008. Demographic and clinical data were evaluated in order to study risk factors and to compare the following different ophthalmological methods: visual acuity, biomicroscopy, fundus examination, retinography, fluorescein angiogram, visual field test and, color vision tests. RESULTS: From 36 patients, 34 (94.4 percent) were female. The mean age was 39.9 ± 9.8 years and the disease duration was 13.9 ± 6.6 years. Besides chronic use of chloroquine, patients also showed high daily and cumulative doses. These high risk factors were not related to a higher retinopathy prevalence. Visual field showed 38.9 percent of retinopathy prevalence. Other ophthalmological methods failed in detecting most cases. CONCLUSION: High prevalence of retinopathy in high risk patients was observed by visual field test, but other ophthalmological methods failed in detecting alterations. Ophthalmological assessment of these patients should include visual field, even in the absence of clinical alterations.