Research progress on chemical constituents and pharmacological effects of Ajania plants / 中国中药杂志

Ajania belonging to the subtribe Artemisiinae of Anthemideae(Asteraceae) is a genus of semi-shrubs closely related to Chrysanthemum. There are 24 species of Ajania in northwestern China, most of which are folk herbal medicines with strong stress tolerance. Modern medical studies have demonstrated that the chemical constituents of Ajania mainly include terpenoids, flavonoids, phenylpropanoids, alkynes, and essential oils. These compounds endow the plants with antimicrobial, anti-inflammatory, antitumor, antimalarial, antioxidant, and insecticide effects. In this study, we reviewed the research progress in the chemical constituents and pharmacological activities of Ajania, aiming to provide reference for the further research and development of Ajania.

Microbial transformation of artemisinin and its derivatives / 中国中药杂志

Microbial transformation is an efficient enzymatic approach for the structural modification of exogenous compounds to obtain derivatives. Compared with traditional chemical synthesis, the microbial transformation has in fact the undoubtable advantages of strong region-and stereo-selectivity, and a low environmental and economic impact on the production process, which can achieve the reactions challenging to chemical synthesis. Because microbes are equipped with a broad-spectrum of enzymes and therefore can metabolize various substrates, they are not only a significant route for obtaining novel active derivatives, but also an effective tool for mimicking mammal metabolism in vitro. Artemisinin, a sesquiterpene with a peroxy-bridged structure serving as the main active functional group, is a famous antimalarial agent discovered from Artemisia annua L. Some sesquiterpenoids, such as dihydroartemisinin, artemether, and arteether, have been developed on the basis of artemisinin, which have been successfully marketed and become the first-line antimalarial drugs recommended by WHO. As revealed by pharmacological studies, artemisinin and its derivatives have exhibited extensive biological activities, including antimalarial, antitumor, antiviral, anti-inflammatory, and immunomodulatory. As an efficient approach for structural modification, microbial transformation of artemisinin and its derivatives is an increasingly popular strategy that attracts considerable attention recently, and numerous novel derivatives have been discovered. Herein, this paper reviewed the microbial transformation of artemisinin and its artemisinin, including microbial strains, culture conditions, product isolation and yield, and biological activities, and summarized the advances in microbial transformation in obtaining active derivatives of artemisinin and the simulation of in vivo metabolism of drugs.

Fixation of pfcrt chloroquine resistance alleles in Plasmodium falciparum clinical isolates collected from unrest tribal agencies of Pakistan / Fixação de alelos de resistência à cloroquina pfcrt em isolados clínicos de Plasmodium falciparum coletados de agitações de agências tribais do Paquistão

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

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

Antimalarials and macrolides: a review of off-label pharmacotherapies during the first wave of the SARS-CoV-2 pandemic

Abstract We critically analyzed clinical trials performed with chloroquine (CQ) and hydroxychloroquine (HCQ) with or without macrolides during the first wave of COVID-19 and discussed the design and limitations of peer-reviewed studies from January to July 2020. Seventeen studies were eligible for the discussion. CQ and HCQ did not demonstrate clinical advantages that justified their inclusion in therapeutic regimens of free prescription for treatment or prophylactic purposes, as suggested by health authorities, including in Brazil, during the first wave. Around August 2020, robust data had already indicated that pharmacological effects of CQ, HCQ and macrolides as anti-SARS-CoV-2 molecules were limited to in vitro conditions and largely based on retrospective trials with low quality and weak internal validity, which made evidence superficial for decision-making. Up to that point, most randomized and nonrandomized clinical trials did not reveal beneficial effects of CQ or HCQ with or without macrolides to reduce lethality, rate of intubation, days of hospitalization, respiratory support/mechanical ventilation requirements, duration, type and number of symptoms, and death and were unsuccessful in increasing virus elimination and/or days alive in hospitalized or ambulatory patients with COVID-19. In addition, many studies have demonstrated that side effects are more common in CQ-or HCQ-treated patients.

Eficacia de la tafenoquina en la profilaxis y tratamiento de la malaria por Plasmodium vivax, revisión sistemática y metaanálisis / Efficacy of tafenoquine in the prophylaxis and treatment of malaria by Plasmodium vivax, systematic review and meta-analysis

Introducción. La tafenoquina fue aprobada en el 2018 por la Food and Drug Administration de Estados Unidos y, en el 2019, por la Therapeutic Goods Administration en Australia. Su administración en dosis única y su mecanismo de acción en las fases aguda y latente han sido objeto de estudio para cambiar el esquema de tratamiento de la malaria por Plasmodium vivax. Objetivo. Evaluar la evidencia científica disponible sobre la eficacia de la tafenoquina en la profilaxis y el tratamiento de la malaria por P. vivax, entre el 2009 y el 2019. Materiales y métodos. Se establecieron los descriptores MeSH y DeCS. Se utilizó la sintaxis ((Malaria Vivax) AND (tafenoquine) AND (prophylaxis)) OR [(Malaria Vivax) AND (tafenoquine) AND (relapse)] en las siguientes bases de datos: Pubmed, The Cochrane Central Register of Controlled Clinical Trials (CENTRAL), ISIS Web of Science, Lilacs y Scopus. Los resultados obtenidos se sometieron a análisis crítico (matriz CASPE). El análisis cuantitativo se realizó utilizando la diferencia de riesgos en análisis de supervivencia (Kaplan-Meier) en los tres artículos finales. Resultados. Se sometieron tres estudios a metaanálisis (Llanos-Cuentas, 2014; Llanos- Cuentas, 2019, y Lacerda, 2019) para evaluar la eficacia del tratamiento con tafenoquina en comparación con primaquina. Se obtuvo una diferencia de riesgo global de 0,04 (IC95% 0-0,08; p=0,07). La tafenoquina no mostró inferioridad en la eficacia del tratamiento frente al esquema de primaquina. Conclusión. La tafenoquina es una alternativa que mejora el cumplimiento del tratamiento, lo que podría acercar a Colombia a las metas de la Estrategia Técnica Mundial contra la Malaria, 2016-2030.

Introduction: Tafenoquine was approved in 2018 by the Food and Drug Administration in the United States and in 2019 by the Therapeutic Goods Administration in Australia. Its administration in a single dose and its mechanism of action in the acute and latent phases of the disease have been studied to change the treatment regimen for Plasmodium vivax malaria. Objective: To evaluate the available scientific evidence of the efficacy of tafenoquine in prophylaxis and treatment between 2009 and 2019. Materials and methods: We established the MeSH and DeCS descriptors and we used the syntax ((Malaria Vivax) AND (tafenoquine) AND (prophylaxis)) OR [(Malaria Vivax) AND (tafenoquine) AND (relapse)] in the following databases: Pubmed, The Cochrane Central Register of Controlled Clinical Trials (CENTRAL), ISIS Web of Science, Lilacs, and Scopus. The results obtained were subjected to critical analysis (CASPE matrix). The quantitative analysis was performed with risk differences in survival analysis (Kaplan Meier) in the final three articles. Results: Three studies underwent meta-analysis (Llanos-Cuentas, 2014; Llanos-Cuentas, 2019, and Lacerda, 2019) to evaluate the efficacy of the treatment with tafenoquine compared to primaquine. A global risk difference of 0.04 was obtained (95% CI: 0.00-0.08; p=0.07). Tafenoquine did not show inferiority in the efficacy of treatment compared to the primaquine scheme. Conclusion: Tafenoquine is a therapeutic alternative to primaquine that improves adherence, which could bring Colombia closer to the goals of the World Technical Strategy against Malaria 2016-2030.

Factores asociados a casos de malaria y plantas medicinales empleadas para su tratamiento en habitantes de Corozal, Colombia / Factors associated with cases of malaria and medicinal plants used for its treatment in inhabitants of Corozal, Colombia

Introducción: La malaria es una de las enfermedades infecciosas más importantes y para tratarla además de medicamentos, la población emplea plantas medicinales. El objetivo fue establecer los factores asociados a malaria y las plantas empleadas para su tratamiento en habitantes de Corozal. Método: Se aplicó una encuesta con preguntas sociodemográficas, de la vivienda, de conocimiento y de actitudes y las plantas medicinales empleadas para tratarla. Resultados: El 48% emplean plantas medicinales solas o con medicamentos, siendo el Gliricidia sepium (matarratón) y el Acmella oppositifolia (yuyo) las plantas más empleadas. En el 48% de las casas ha habido malaria. Por regresión logística se estableció que la malaria se asoció con conocer cómo se adquiere, consultar al médico tradicional y tener más de 15 años en Corozal. Conclusiones: Las plantas que la población de este estudio reportan no muestran evidencia científica como antimalaricos. Es importante una mayor presencia de las autoridades de salud y su trabajo conjunto con el médico tradicional para lograr estrategias más efectivas(AU)

Introduction: Malaria is one of the most important infectious disease and to treat it in addition to medicines the population uses medicinal plants. The objective was to establish the factors associated with malaria and the plants used for its treatment in inhabitants of Corozal. Method: A survey was applied with sociodemographic questions about housing, knowledge and attitudes, in addition to the medicinal plants used to treat it. Results: 48% use medicinal plants alone or with medicines, Gliricidia sepium (rat poisson) and Acmella oppositifolia (Opposite-leaf Spotflower) are the most used. In 48% of the homes there has been malaria. By logistic regression it was established that malaria was associated with knowing how it is acquired, consulting the traditional doctor and living in Corozal for more than 15 years. Conclusions: The plants that the population of this study report usimg do not show scientific evidence antimalarials. A greater presence of health authorities and their joint work with the traditional doctor for more effective strategies is important(AU)

Prevalencia de malaria en Aguarico, comunidad de la Amazonía ecuatoriana / Malaria prevalence in Aguarico, a community in the Ecuadorian Amazon

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

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

Quantitative standardization of pharmacologically active components from antiplasmodial plant Solanum nudum Dunal (wild and in vitro) / Estandarización cuantitativa de componentes farmacológicamente activos de la planta antiplasmodial Solanum nudum Dunal (silvestre e in vitro)

Solanum nudum Dunal (Solanaceae) is most commonly known andused by the population of the colombian Pacific coast as an antimalarial treatment. This article study into optimization and quantitative analysis of compounds steroidal over time of development of this species when grown in vitro and wild. A new steroidal compound named SN6 was elucidated by NMR and a new method of quantification of seven steroidal compounds (Diosgenone DONA and six steroids SNs) using HPLC-DAD-MS in extracts of cultures in vitroand wild was investigated. Biology activity of extracts was found to a range of antiplasmodial activity in FCB2 and NF-54 with inhibitory concentration (IC50) between (17.04 -100µg/mL) and cytotoxicity in U-937 of CC50 (7.18 -104.7µg/mL). This method creates the basis for the detection of seven sterols antiplasmodial present in extracts from S. nudum plant as a quality parameter in the control and expression of phytochemicals.

Solanum nudum Dunal (Solanaceae) es el más conocido y utilizado por la población de la costa del Pacífico colombiano como tratamiento antipalúdico. Este artículo estudia la optimización y el análisis cuantitativo de compuestos esteroides a lo largo del tiempo de desarrollo de esta especie cuando se cultiva in vitro y en forma silvestre. Un nuevo compuesto esteroideo llamado SN6 fue dilucidado por RMN y se investigó un nuevo método de cuantificación de siete compuestos esteroides (Diosgenone DONA y seis esteroides SN) usando HPLC-DAD-MS en extractos de cultivos in vitro y silvestres. La actividad biológica de los extractos se encontró en un rango de actividad antiplasmodial en FCB2 y NF-54 con concentración inhibitoria (IC50) entre (17.04 -100 µg/mL) y citotoxicidad en U-937 de CC50 (7.18 -104.7 µg/mL). Este método crea la base para la detección de siete esteroles antiplasmodiales presentes en extractos de planta de S. nudum como parámetro de calidad en el control y expresión de fitoquímicos.

In vivo antimalarial activity of self-nanoemulsifying drug delivery systems containing ethanolic extract of Morinda lucida in combination with other Congolese plants extracts

Abstract Morinda lucida leaves are largely used by Congolese traditional healers for the treatment of uncomplicated malaria. The antimalarial activity of their ethanolic extract has been confirmed both in vitro and in vivo. However, the development of relevant formulations for potential clinical application is hampered since the active ingredients contained in this extract exhibit poor water solubility and low oral bioavailability. Hence, this work aims not only to develop self-nanoemulsifying drug delivery systems (SNEDDSs) for oral delivery of the ethanolic extract of Morinda lucida (ML) but also to evaluate its oral antimalarial activity alone and in combination with other Congolese ethanolic plant extracts (Alstonia congensis, Garcinia kola, Lantana camara, Morinda morindoides or Newbouldia laevis). Based on the solubility of these different extracts in various excipients, SNEDDS preconcentrates were prepared, and 200 mg/g of each plant extract were suspended in these formulations. The 4-day suppressive Peter's test revealed a significant parasite growth inhibiting effect for all the extract-based SNEDDS (from 55.0 to 82.4 %) at 200 mg/kg. These activities were higher than those of their corresponding ethanolic suspensions given orally at the same dose (p<0.05). The combination therapy of MLSNEDDS with other extract-based SNEDDS exhibited remarkable chemosuppression, ranging from 74.3 % to 95.8 % (for 100 + 100 mg/kg) and 86.7 % to 95.5 % (for 200 + 200 mg/kg/day). In regard to these findings, SNEDDS suspension may constitute a promising approach for oral delivery of ML alone or in combination with other antimalarial plants.

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.

Clinical and haematological determinants of outcome among children with cerebral malaria in a tertiary centre in Nigeria

Background: Many clinical and haematological changes occur as a result of severe malaria, of which cerebral malaria (CM) is a common entity. These changes affect virtually all organs and systems of the body. We identify various clinical and haematological determinants of outcome in CM so as to institute proactive management of such children.Methods: All children who met World Health Organization (WHO) diagnostic criteria for CM over 8 month-period were prospectively studied. The presenting symptoms and its duration, detailed physical examination and laboratory parameters were obtained. Logistic regression was employed to determine the prognostic significance of various clinical and laboratory parameters. Outcome indicators were full recovery, alive with neurological sequelae or death of the children. Results: Of the 892 children admitted into the Children Emergency Unit (CEU) over the study period, 50 (5.6%) had CM with M: F ratio of 1:1 and age range of 6 months to 12 years. Sixty percent were aged less than 5 years. The defining symptoms were fever (100%), coma (100%) and convulsion (98%). Forty-one (82%) patients survived, while nine (18%) died. Of the 41 survivors, 30 (73.2%) recovered fully, while 11 (26.8%) had neurological deficits at discharge. Identified clinical and laboratory predictors of mortality and neurological sequelae in CM included Blantyre coma score of 0-2(p = 0.018) prolonged coma recovery time > 26 hours (p = 0.026), abnormal breathing pattern (p = 0.0124), absent corneal reflex (p = 0.012), absent pupillary reflex (p = 0.012), depressed tendon reflex (p = 0.028), hyperreflexia (p =0.014), retinal haemorrhage (p =0.001), duration of admission (p=0.000), hyper parasitaemia (p=0.001), hypoglycemia (p= 0.014) and leucocytosis (p = 0.008). Independent determinants of immediate post-recovery neurological deficits and death were hyper-parasitaemia (OR = 8.657, p = 0.017.) and leucocytosis (OR = 1.090; p = 0.035 Conclusion: CM is a potentially reversible encephalopathy associated with high mortality and sequelae. Affected children with the above listed clinical / haematological parameters especially hyperparasitemia and leucocytosis should be given proactive management to improve the outcome.

Prevalence and Determinants of the use of Enema in under-five children in Akwa Ibom State

Background: Use of enema in children across clinical and community settings are associated with risks. This study seeks to determine the prevalence of enema practice in under-five children, substances used as enema and the reasons for enema practice by mothers. Materials and Methods: This was a descriptive cross sectional study among 252 consecutively recruited mothers of under-five children attending immunization/well babies clinics in 2 health centres in Akwa Ibom state using a semi-structured self and interviewer administered questionnaire for data collection. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 17.0 at a level of significance of P<0.05. Results: One hundred and sixty-nine (67.1%) respondents had ever given enema to their children. Mothers (69.2%) administered enema to their children which most often (72.8%) was recommended to them by others. Herbal enema was preferred to chemical and plain water enema. Common reasons for enema administration were in preparation for administration of antimalarial to ensure its effectiveness (60.4%), to relief constipation (49.7%) and abdominal pains (46.7%) and treatment of fevers (41.4%). Predictors of enema practice were age of the child (OR 0.4, 95% CI 0.212-0.765, p=0.005) and ethnic origin of the mothers (OR 9.4,95% CI 4.024-22.104, p<0.001). Conclusion: The practice of enema is common in the study area. Health practitioners should be aware of this practice in the communities, seek for this history during clinical consultation and make concerted effort in educating the mothers and other caregivers against this practice.

The current use of the artemisinin-based combination therapies in adult patients at a tertiary hospital, South-South Nigeria

Objective:The antimalarial preferences, tolerability, and cost of the Artemisinin-based combination therapies (ACTs) among adult patients and caregivers are largely understudied despite being the recommendedtreatment for Plasmodium falciparum.We, therefore, evaluated antimalarial preferences, tolerability, and cost of the ACTs among adult patients attending the University of Benin Teaching Hospital, Nigeria. Methods:This was a cross-sectional study conducted among adult patients and their caregivers atthe University of Benin Teaching Hospital, Nigeria,using a semi-structured questionnaire. Their preferred antimalarial medication, previous use of antimalarial monotherapies, current ACT use; cost considerations, and adverse effects profile were sought.Result:Six hundred respondents were recruited with a mean age of 41.4±16.3years and M/F ratio of 1.4. The majority (88.0%), reported that they had between 1-5 episodes of malaria fever in a year. Only 28.2% received doctors' prescriptions while 85.8% purchased their antimalarial medications from a pharmacy. Sixty percent of the respondents used at least one ACT; mainly Artemether-Lumefantrine (AL) 312(52.0%). Only 9.3% reported previous adverse effects with the ACTs with 4.0% of respondents discontinuing their medications. The mean (SD) cost of purchasing ACTs was 1,516.47±760.3 (3.65 USD) Naira.Conclusion: This study showed adult patients' preference for the ACTs, especially Artemether-Lumefantrine despite some inclination towards antimalarial monotherapies and parenteral route. There was also a high rate of use of malaria presumptive treatment, but only a few reported adverse effects. There is a need to make ACTs affordable because the cost is still presently high for most Nigerians.

Seasonal malaria chemoprevention coverage in Burkina Faso in 2018: Descriptive analysis of mothers' knowledge and attitude during cross sectional survey

Seasonal malaria chemoprevention (SMC) is effective to prevent malaria in children 3 to 59 months in the Sahel region. Mother's seasonal malaria chemoprevention related knowledge and attitudes and the coverage of the strategy among targeted children were assessed. A cross-sectional survey was conducted in 1828 children aged 3 to 59 months from November 7 to 18, 2018 in eight health regions of Burkina Faso where SMC was implemented with Malaria Consortium supported fund. Data were collected using structured questionnaire and direct inspection of SMC card. MAGPI software was used for data collection and STATA 12.0 was used for the analysis. A total of 1828 children 3 to 59 months were enrolled and 951 mothers interviewed on different aspects of SMC. Overall, the SMC coverage was high for single cycle or for cumulative coverage basis. Single cycle coverage increased over rounds, from mother and tutor's interview (from 87.09% (1592/1828) to 91.19% (1667/1828); p=0.001). Over 91.18% (869/951) knew that SMC objective was to prevent malaria. Overall SMC was well tolerated and most 95.2% (296/320) of mothers and tutors surveyed owned treated bed nets. Despite combining high coverage and treated bed-net use, at least 16.19% remained rapid diagnosis test positives during the survey. SMS coverage was high in the current survey and most mothers knew the relevance of SMC administration with high bed-net coverage.

Factors associated with community engagement in areas with high and low incidence of local malaria cases in Zanzibar

Introduction: the prevalence of asymptomatic infection in the general population in Zanzibar has declined from above 25% in 2005 to less than 1% in 2010. Despite these achievements, in 2021, the number of malaria cases increased by two folds. This study aimed at understanding the levels of community engagement towards malaria elimination and factors associated with them to provide recommendations that can be used to reinforce community engagement. Methods: a descriptive cross-sectional survey was conducted using structured questionnaires to 431 randomly selected households. The interviewees were the heads of households or representative adults above 18 years. Univariate and multivariate analysis was done to determine the association between social demographic characteristics, malaria knowledge, practicing malaria prevention interventions and status of community engagement. Statistical significance test was declared at P- value <0.05. Results: of all respondents, 261 (60.6%) were not engaged in either planning or implementation of malaria interventions, of which 120 (45.9%) participants were in the high malaria transmission and 141 (54.0%) from the low malaria transmission (P=0.018). Factors significantly associated with increased odds of community engagement were the level of knowledge on malaria (P= 0.002) and factors independently associated with reduced odds of community engagement was the level of malaria burden (P= 0.01). Conclusion: level of malaria knowledge and malaria burden were associated with community engagement. There is a need to increase malaria knowledge in the community based on the existing gaps as this study suggests that having high malaria knowledge can significantly contribute to increased opportunity for community engagement.

Prevalence of antifolate drug resistance markers in Plasmodium vivax in China / 医学前沿

The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax, as antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009-2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.

Primer consenso cubano sobre el uso de terapia convencional y biológica en pacientes con artritis reumatoide / First Cuban consensus on the use of conventional and biological therapy in patients with rheumatoid arthritis

resumen está disponible en el texto completo

Introduction: The development of recommendations for the treatment of rheumatoid arthritis (RA) in the Cuban context may be one of the ways to achieve better control of this disease. Objective: To reach a consensus and update relevant aspects of conventional and biological RA modifier therapy in Cuba. Methods: 18 specialists from 8 Cuban provinces, experts in RA care, were summoned, according to the years of dedication to the specialty, the conferences on this topic and their publications. The first meeting took place in March 2016 in the provincial hospital of Villa Clara, Cuba, with the participation of all the experts. A review of the literature on conventional and biological therapy previously collected by the participants was developed, and two teams were formed: the first would address everything related to conventional therapy in RA (HRCT) and the other, biological therapy in RA (TBAR). Three questionnaires related to the use of corticosteroids, HRCT and TBAR, were prepared, answered by the participants via email. In a second meeting, held in October 2016 in Havana, the analysis of all the responses provided was carried out. Questions with a response of 90% or more votes were considered as recommendations. Results: The questionnaires were answered by 95% of the participants. 9 recommendations and 1 algorithm were established. The recommendations are as follows: methotrexate is the drug of choice in the treatment of RA after diagnosis; The administration of another conventional drug (DMARDc) (azathioprine, salazosulfapyridine, antimalarials and leflunomide) is recommended in patients with a diagnosis of active RA in whom methotrexate is contraindicated or there is a failure in response - consider the administration of low doses of prednisone or equivalent (<7.5 mg/d) associated with DMARDc in patients with active moderate to severe RA, for the shortest possible time; perform serological control including tests for hepatitis B and C viruses and screening for HIV in all patients diagnosed with RA before starting treatment with DMARDc and biologics; in patients in remission or, at least, with a DAS-28 below 3.2, consideration should be given to withdrawing one of the DMARDs or reducing, to the minimum possible expression, the dose of both disease modifiers; if methotrexate fails, tocilizumab in combination with methotrexate or as monotherapy will be indicated. Conclusions: Aspects related to conventional therapy with methotrexate, azathioprine, salazosulfapyridine, antimalarials and leflunomide were agreed. The value of early diagnosis and immediate initiation of DMARDc therapy and the use of glucocorticoids was analyzed. Treatment with tocilizumab, the only biological available in Cuba against RA, will be administered when there is a failure in the response to conventional therapy and combinations between these drugs. It is recommended to hold educational conferences through the mass media aimed at patientshttp(AU)

Guía de práctica clínica para el tratamiento farmacológico de nefritis lúpica / Clinical practice guideline for the pharmacological treatment of lupus nephritis

La nefritis lúpica (NL) es un tipo de glomerulonefritis que se desarrolla como consecuencia del lupus eritematoso sistémico (LES), una enfermedad autoinmune sistémica de presentación clínica variable (1, 2). La NL se clasifica histológicamente en seis clases(I-VI) (3), las cuales poseen diferentes manifestaciones clínicas y expresan diferentes grados de gravedad del daño renal (1). En este documento no se abordará a pacientes con clase VI pues solo son tributarios a terapia de reemplazo renal. La NL se presenta aproximadamente en el 50 a 60% de las personas con LES, en quienes es una de las principales causas de morbimortalidad puesto que progresa a falla renal o muerte (1, 2). En suma, la prevalencia, gravedad y mortalidad de la NL son mayores en hispanos, afroamericanos, y asiáticos (4). El tratamiento farmacológico de la NL consta de las fases de inducción y mantenimiento (1). Entre los fármacos principalmente utilizados durante estas fases, se encuentran los antimaláricos, glucocorticoides (GC), inmunosupresores como micofenolato mofetilo (MMF) y ciclofosfamida (CYC) endovenosa, entre otros (1, 2). Sin embargo, la incidencia de respuesta renal completa suele ser baja (~20 a 30%) (1, 5, 6), y tanto las recaídas como los eventos adversos pueden ser frecuentes con estas terapias (1). Por ello, actualmente se ha propuesto el uso de diferentes dosis de dichos fármacos y otros inmunosupresores ya sea solos o en combinación. La evaluación de los beneficios y daños de estos fármacos permitirá conocer cuáles son las opciones más eficaces y seguras que logren inducir la remisión de la enfermedad, prevenir las recaídas, prevenir la progresión a falla renal y disminuir la mortalidad de los adultos con diagnóstico reciente de NL. Por ello, el Seguro Social de Salud (EsSalud) priorizó la realización de la presente guía de práctica clínica (GPC) para establecer lineamientos basados en evidencia con el fin de gestionar de la mejor manera los procesos y procedimientos asistenciales de la presente condición. Esta GPC fue realizada por la Dirección de Guías de Práctica Clínica, Farmacovigilancia y Tecnovigilancia del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) de EsSalud.

Desarrollo y validación interna de un modelo de predicción clínica del riesgo de infección bacteriana nosocomial en pacientes con lupus eritematoso sistémico / Development and internal validation of a clinical prediction model of the risk of nosocomial bacterial infection in patients with systemic lupus erythematosus

RESUMEN Introducción: Los pacientes con lupus eritematoso sistémico (LES) tienen un riesgo aumen tado de padecer infecciones tanto adquiridas en la comunidad como asociadas con el cuidado de la salud. Las infecciones bacterianas son las más frecuentes y graves durante la hospitalización de estos pacientes. Objetivo: Desarrollar y validar internamente un modelo de predicción clínica de pronóstico del riesgo de infección bacteriana adquirida en el hospital en pacientes con LES, usando datos clínicos y de laboratorio obtenidos durante las primeras horas de hospitalización. Métodos: Se analizó una cohorte retrospectiva de pacientes con LES mayores de 16 arios, hos pitalizados por motivos diferentes a infección bacteriana en 2 hospitales de alta complejidad de Medellín entre 2011 y 2016. Se compararon las características de los pacientes que des arrollaron el desenlace de infección bacteriana entre el día 3 y el día 15 de hospitalización con aquellos que no lo presentaron. Las variables significativas en el análisis bivariado fueron consideradas para la construcción del modelo por medio de regresión logística multivariada. Resultados: Se incluyeron 765 episodios, de los cuales 98 (12,8%) presentaron el desenlace de interés. Se consideraron 35 predictores candidatos. Las variables incorporadas en el modelo final fueron: edad, recuento de neutrófilos, puntaje de actividad lúpica SLEDAI, uso de sonda vesical, uso de catéter venoso central en las primeras 72 h, dosis de glucocorticoides en el mes previo y el uso de un antimalárico en los 3 meses previos. La capacidad de discrimi nación del modelo fue aceptable a buena (AUC-ROC 0,74; IC 95% 0,69-0,80). La prueba de bondad de ajuste de Hosmer-Lemeshow (p = 0,637) evidenció una adecuada calibración. Conclusión: Desarrollamos un modelo de predicción clínica de pronóstico del riesgo de infec ción bacteriana nosocomial en pacientes con LES. El modelo desarrollado está compuesto por variables clínicas y de laboratorio simples disponibles en el momento del ingreso al hospital. Se requieren estudios de validación externa y de impacto clínico antes de su implementación rutinaria.

ABSTRACT Introduction: Patients with systemic lupus erythematosus (SLE) have an increased risk of developing community-acquired infections, as well as those associated with health care. Bacterial infections are the most common and serious while these patients are in hospital. Objective: To develop, and internally validate, a clinical prediction model for the prognosis of the risk of hospital-acquired bacterial infection in SLE patients using clinical and laboratory data obtained during the first hours of hospital admission. Methods: An analysis was performed on retrospective cohort of patients with SLE older than 16 years and admitted for reasons other than bacterial infection in 2 highly complex hospitals in Medellín between 2011 and 2016. The characteristics of the patients who developed a bacterial infection were compared between day 3 and day 15 of hospital admission with those who did not develop one. The significant variables in the bivariate analysis were used for the construction of the model using multivariate logistic regression. Results: A total of 765 episodes were included, of which 98 (12.8%) presented the outcome of interest. Thirty-five candidate predictors were considered. The variables incorporated in the final model were: age, neutrophil count, SLEDAI lupus activity score, use of a bladder catheter, use of a central venous catheter in the first 72 h, glucocorticoid doses in the previous month, and use of an antimalarial drug in the 3 previous months. The discrimination capacity of the model was acceptable to good (AUC-ROC 0.74; 95% CI 0.69-0.80). The Hosmer-Lemeshow goodness of fit test (P = .637) suggested adequate calibration. Conclusion: A clinical prediction model of prognostic risk of nosocomial bacterial infection in patients with SLE has been developed. This model is made up of simple clinical and laboratory variables available at the time of hospital admission. External validation and clinical impact studies are required before routine implementation.