[Emergencies in infectious diseases]. / Infektiologische Notfälle.

This article aims to provide an overview of common and high-impact medical emergencies that require prompt and effective infectious diseases management. In the described clinical scenarios of malaria, sepsis, necrotizing fasciitis, and meningitis the authors have emphasized the crucial importance of rapid and accurate diagnosis, as well as appropriate treatment from the perspective of infectious diseases. All of these emergencies demand a high degree of clinical suspicion for accurate diagnosis. Some of them also necessitate the involvement of other medical disciplines, such as neurology in the case of meningitis or surgery for necrotizing fasciitis. Additionally, implementing the right empiric antibiotic regimen or, in the case of malaria, antiparasitic treatment is crucial for improving patient outcomes. As patients with these diagnoses may present at any outpatient department, and efficient and quick management is essential, a deep understanding of diagnostic algorithms and potential pitfalls is of the utmost importance.

[Emergencies in infectious diseases]. / Infektiologische Notfälle.

This article aims to provide an overview of common and high-impact medical emergencies that require prompt and effective infectious diseases management. In the described clinical scenarios of malaria, sepsis, necrotizing fasciitis, and meningitis the authors have emphasized the crucial importance of rapid and accurate diagnosis, as well as appropriate treatment from the perspective of infectious diseases. All of these emergencies demand a high degree of clinical suspicion for accurate diagnosis. Some of them also necessitate the involvement of other medical disciplines, such as neurology in the case of meningitis or surgery for necrotizing fasciitis. Additionally, implementing the right empiric antibiotic regimen or, in the case of malaria, antiparasitic treatment is crucial for improving patient outcomes. As patients with these diagnoses may present at any outpatient department, and efficient and quick management is essential, a deep understanding of diagnostic algorithms and potential pitfalls is of the utmost importance.

Association of G6PD status and haemolytic anaemia in patients receiving anti-malarial agents: a systematic review and meta-analysis.

BACKGROUND: Some anti-malarial drugs often cause haemolytic anaemia in glucose-6-phosphate-dehydrogenase deficiency (G6PDd) patients. This study aims to analyse the association of G6PDd and anaemia in malaria patients receiving anti-malarial drugs. METHODS: A literature search was performed in major database portals. All studies searched using keywords with Medical Subject Headings (MeSH) were included, without date or language restriction. Pooled mean difference of haemoglobin and risk ratio of anaemia were analysed using RevMan. RESULTS: Sixteen studies comprising 3474 malaria patients that included 398 (11.5%) with G6PDd were found. Mean difference of haemoglobin in G6PDd/G6PD normal (G6PDn) patients was - 0.16 g/dL (95% CI - 0.48, 0.15; I2 5%, p = 0.39), regardless of the type of malaria and dose of drugs. In particular with primaquine (PQ), mean difference of haemoglobin in G6PDd/G6PDn patients with dose < 0.5 mg/kg/day was - 0.04 (95% CI - 0.35, 0.27; I2 0%, p = 0.69). The risk ratio of developing anaemia in G6PDd patients was 1.02 (95% CI 0.75, 1.38; I2 0%, p = 0.79). CONCLUSION: Single or daily standard doses of PQ (0.25 mg/kg/day) and weekly PQ (0.75 mg/kg/week) did not increase the risk of anaemia in G6PDd patients.

Investigations of socioeconomic factors associated with follow-up compliance with malaria treatment in Haiti.

OBJECTIVE: To identify factors affecting compliance with follow-up during treatment in confirmed malaria patients at two health centers in Haiti. METHODS: A prospective observational study of malaria patients undergoing treatment over a six-week period. Patients' return visits (follow-up visits) to the health centers for consultation in accordance with the physicians' requests were recorded and used to determine compliance. Socioeconomic data were obtained from patient enrollment questionnaires and through post-treatment interviews. The management practices and procedures at the health centers to retain patients were also reviewed. Descriptive statistics and Spearman's rank correlation were used to identify significant factors, which were used as variables in a logistic regression model. RESULTS: Sixty-eight percent of the malaria patients completed follow-up, with higher compliance being recorded in the larger, more established health center of Leogane (67%) than Cite Soleil (33%). The patient socioeconomic profiles differed between the two health center locations by level of education, religious diversity, household size, and percentage of married individuals. Crude logistic regression analyses identified health center location (OR = 0.179 [95% CI 0.064, 0.504]) and household size (OR = 1.374 [95% CI 1.056, 1.787]) to be associated with compliance. The adjusted model only identified health center location (OR = 0.226 [95% CI 0.056, 0.918]) as significantly associated with compliance. CONCLUSION: Although patients' household size may be important according to the crude logistic regression analysis, in the adjusted analysis the site location of the health center where patients receive treatment was identified as the only important factor associated with follow-up compliance in malaria patients during treatment in Haiti. This information might be helpful to improve treatment outcomes and contribute to the monitoring of antimalarial resistance in Haiti.

Optical mesoscopy, machine learning, and computational microscopy enable high information content diagnostic imaging of blood films.

Automated image-based assessment of blood films has tremendous potential to support clinical haematology within overstretched healthcare systems. To achieve this, efficient and reliable digital capture of the rich diagnostic information contained within a blood film is a critical first step. However, this is often challenging, and in many cases entirely unfeasible, with the microscopes typically used in haematology due to the fundamental trade-off between magnification and spatial resolution. To address this, we investigated three state-of-the-art approaches to microscopic imaging of blood films which leverage recent advances in optical and computational imaging and analysis to increase the information capture capacity of the optical microscope: optical mesoscopy, which uses a giant microscope objective (Mesolens) to enable high-resolution imaging at low magnification; Fourier ptychographic microscopy, a computational imaging method which relies on oblique illumination with a series of LEDs to capture high-resolution information; and deep neural networks which can be trained to increase the quality of low magnification, low resolution images. We compare and contrast the performance of these techniques for blood film imaging for the exemplar case of Giemsa-stained peripheral blood smears. Using computational image analysis and shape-based object classification, we demonstrate their use for automated analysis of red blood cell morphology and visualization and detection of small blood-borne parasites such as the malarial parasite Plasmodium falciparum. Our results demonstrate that these new methods greatly increase the information capturing capacity of the light microscope, with transformative potential for haematology and more generally across digital pathology. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

High Prevalence of Low-Level Parasitemia With Plasmodium vivax in Makira-Ulawa Province Presents a Challenge for the Diagnosis and Eradication of Malaria in Solomon Islands.

Background: Malaria remains endemic in Solomon Islands, but data on malaria in the provinces of Solomon Islands are limited. This study from Makira-Ulawa Province aimed to identify the most prevalent strain of malaria and assess if the available rapid diagnostic test (RDT) was effective in Kirakira Hospital. Methods: Forty-five patients who presented to Kirakira Hospital with symptoms of fever had a positive malaria parasite smear during a 4-week period in 2017. The parasite count for each smear was calculated. Simultaneous testing using the CareStart Malaria HRP2/pLDH (Pf/pan) Combo RDT was conducted. The data for all malaria parasite smears performed in Makira-Ulawa Province in 2016 were collated for comparison. Results: All 45 patients diagnosed with malaria in a 4-week period in 2017 were positive for Plasmodium vivax. The median parasite load was 280 parasites per µL (range, 160 to 640 parasites per µL). None of the 45 CareStart RDTs performed was positive. In 2016, 5,505 of 17,195 patients (32.0%) screened had malaria parasites detected on a malaria parasite smear. P vivax was detected in 5,212 (94.7%) and Plasmodium falciparum in 285 (5.2%) of patients with malaria. Conclusion: P vivax is the predominant strain of malaria present in Makira-Ulawa Province. RDTs were not helpful in the diagnosis of malaria at Kirakira Hospital. The parasite load detected in the 45 patients diagnosed with malaria in this study was low. A focus on attempting to eradicate P vivax in the community through improved compliance with treatment protocols is suggested as a possible way forward to best manage malaria in Makira-Ulawa Province.

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

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

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

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

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

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

An intricate case of multidrug resistant Plasmodium falciparum isolate imported from Cambodia.

BACKGROUND: Imported cases of multidrug resistant Plasmodium falciparum and treatment failure with artemisinin-based regimens, although rare, have been described also in Western countries and their management is often challenging. This is also due to an inadequate knowledge and implementation of health prevention measures. CASE REPORT: A complex case of imported malaria caused by Plasmodium vivax/P. falciparum isolates in a patient who was not taking chemoprophylaxis while he was travelling in Cambodia is reported in this article. After failures of artemisinin-based and both oral and intravenous quinine-based regimens, a multidrug resistant P. falciparum was detected. The patient was successfully treated with atovaquone-proguanil. CONCLUSIONS: This experience highlights the importance of a careful management that should be based not only on the most up-to-date guidelines, but also on the awareness of a rapidly evolving scenario.

Comparative Study on Antenatal and Perinatal Outcome of Vivax and Falciparum Malaria in a Tertiary Care Hospital of Kolkata, India.

INTRODUCTION: Malaria occurring in pregnancy is associated with considerable maternal and perinatal morbidity. In India, the problem is compounded by dual parasitological aetiology of Plasmodiumvivax (P.vivax) and Plasmodium falciparum (P.falciparum). AIM: To compare the outcome of infections by P. vivax and P.falciparum species among pregnant women in a hospital setting. MATERIALS AND METHODS: Pregnant women who tested positive for malaria either by microscopy of peripheral blood smear or ELISA test for double antigen were enrolled in the study. They were followed up till their delivery and discharge from hospital. Demographic, clinical and laboratory data was collected at enrolment, on event of complication and at delivery. Data was analyzed for univariate and multivariate associations. RESULTS: There were 64 pregnant women diagnosed with malaria. A total of 76.6% study subjects had vivax infection rest were infected with p. falciparum. Anaemia (84%) was the commonest complication. A total of 60.9% women had pathological placenta. Preterm delivery, low birth weight and Apgar score <7 were the adverse pregnancy outcomes which were more frequent with falciparum infection. There were three perinatal deaths. Multigravidas were at significantly higher risk for low birth weight and low Apgar score of newborn. Infection in later trimester was associated with low Apgar score. CONCLUSION: Both types of malaria cause considerable morbidity in pregnant women. More cases occurred among primigravida but multigravida and later trimester of pregnancy had more severe disease.

Blackwater Fever Followed by Severe Falciparum Malaria in a Child

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

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

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

Plasmodium vivax infection impersonating Plasmodium falciparum malaria.

A 73-year-old woman came to the casualty ward with symptoms of syncopal attacks, weakness, fever with chills and rigors. A provisional diagnosis of Plasmodium vivax malaria was made after the blood investigations. She had deranged renal function tests, altered sensorium and low platelet count. Repeated tests for P. falciparum (Card test) were negative. Glucose-6-Phosphate dehydrogenise (G6PD) levels were within normal limits. Treatment for P. vivax was started with intravenous quinine initially followed by oral quinine for a period of seven days and patient responded to the treatment and was discharged within 2 weeks of admission. Most of the cases of P. vivax present with typical and predictable features, although atypical cases with characteristics of P. falciparum can occur, especially in the elderly.

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

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

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

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

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

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

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

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

Comparison of the Clinical Profile and Complications of Mixed Malarial Infections of Plasmodium Falciparum and Plasmodium Vivax versus Plasmodium Falciparum Mono-infection.

OBJECTIVES: This study aimed to compare the clinical presentations and complications in patients having mixed malaria infection of Plasmodium falciparum and Plasmodium vivax with those of patients with malaria due to a P. falciparum mono-infection. METHODS: The medical records of malaria patients admitted to Kasturba Medical College, Manipal, India, during the years 2008-10 were analysed. Inclusion criteria were patients in whom P. falciparum and P. vivax coinfection or P. falciparum mono-infection alone was confirmed on peripheral smear examination. Exclusion criteria were patients in whom P. vivax infection alone was diagnosed on peripheral smear examination. The sample size was twenty patients diagnosed with mixed infection of P. falciparum and P. vivax and 60 patients diagnosed with P. falciparum mono-infection. RESULTS: 35% of mixed infections had thrombocytopenia as compared to 51.7% of P. falciparum mono-infections. A total of 5% of the mixed infections had renal failure as compared to 16.7% of the falciparum mono-infections. Total bilirubin was raised in 15.8% of mixed infections and in 46.6% of falciparum mono-infections. Abnormal liver enzymes were seen in 36.8% of mixed infections and in 66.6% of falciparum mono-infections. None of the mixed infections had a parasite index over 2% while it was present in 28% of the falciparum mono-infections. CONCLUSION: Patients with mixed infections were found to have a lower incidence of severe complications such as anaemia, thrombocytopenia, liver and renal dysfunction and a lower parasite index. Thus mixed malaria tends to have a more benign course as compared to malaria due to P. falciparum mono-infection.

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

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

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

Effect of quinine therapy on plasma glucose and plasma insulin levels in pregnant women infected with Plasmodium falciparum malaria in Gezira state

To determine if quinine has a metabolic effect during treatment of severe or complicated malaria, we studied its effects on plasma glucose and plasma insulin levels in 150 pregnant women with malaria referred to Madani maternity teaching hospital, Gezira state and 50 healthy pregnant controls. Levels were determined at baseline [day 0] before the start of quinine treatment, after 2 days of treatment [2 hours after the 4th dose] and after 7 days of treatment [day 8]. There was a statistically significant increase in plasma insulin concentrations during the quinine infusion and fall in plasma glucose concentration [P<0.001]. Quinine administered at the recommended dose and rate can disrupt plasma glucose homeostasis although it is still the drug of choice for severe and complicated malaria in Sudan

Quimioterapia antimalárica experimental e mecanismos de ação de antimaláricos envolvendo íons cálcio e prótons

Limitações atuais do arsenal terapêutico na malária humana exigem a busca de novos medicamentos. Além da grande importância econômica e social da malária e da resistência do P. falciparum a cloroquina e outros derivados quinolínicos, as associações medicamentosas compostas por artemisinina e seus derivados apresentam custos de produção elevados, dificultando seu emprego em regiões em desenvolvimento, especialmente no continente africano. Nesse trabalho testamos a atividade antimalárica de: (i) associações dos antimaláricos artesunato (AS) e mefloquina (MQ) com ciprofloxacina, uma fluoroquinolona sintética empregada contra infecções bacterianas; (ii) moléculas obtidas por síntese química, como anti-retrovrais, endoperóxidos, e uma nova molécula híbrida denominada MEFAS e (iii) extratos e compostos purificados de plantas medicinais como falsas quinas e Holostylis reniformis, utilizadas popularmente no tratamento de quadros febris e dispepsias. Os testes esquizonticidas foram feitos em cultivos contínuos de P. falciparum avaliando-se o crescimento das fases intraeritrocitárias através de duas metodologias (teste tradicional ou o ensaio de incorporação de hipoxantina tritiada); e utilizando camundongos inoculados com P. berghei. Estabelecemos ainda um protocolo com sondas fluorescentes que permitiu trabalhar com trofozoítos de P. falciparum viáveis em eritrócitos infectados e acompanhar, em tempo real, ações de potenciais antimaláricos sobre a homeostasia iônica dos parasitos, identificando possíveis alvos intracelulares dos mesmos.

Observamos um sinergismo das associações de MQ e/ou AS com ciprofloxacina, combinações essas que representam uma alternativa promissora para o tratamento da malária humana, assim como os anti-retrovirais testados, todos parcialmente ativos. MEFAS, uma nova molécula híbrida entre os antimaláricos MQ e AS mostrou intensa ação antimalárica in vitro e in vivo. Estudos do mecanismo de ação através de microscopia confocal da MEFAS mostram que a molécula atua simultâneamente em dois compartimentos intracelulares de P. falciparum, o retículo endoplasmático liso e o vacúolo digestivo. Dois endoperóxidos sintéticos derivados do ácido abiético, também ativos na malária, agiram sobre o retículo endoplasmático liso do parasito, mas necessitam de modificações químicas visando potenciar sua ação esquizonticida. Avaliamos ainda a atividade farmacológica de extratos de R. ferruginea e S. pseudoquina que inibiram parcialmente a parasitemia em camundongos e/ou o crescimento de P. falciparum in vitro e de lignanas isoladas de H. renformis que mostrou intensa atividade antimalárica. O conhecimento científico gerado neste trabalho deverá contribuir para a formulação de novos fármacos com ação antimalárica seletiva