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)

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.

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.

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.

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.

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.

Quinolinotriazole antiplasmodials via click chemistry: synthesis and in vitro studies of 7-Chloroquinoline-based compounds

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

Atovaquone, chloroquine, primaquine, quinine and tetracycline: antiproliferative effects of relevant antimalarials on Neospora caninum / Atovaquona, cloroquina, primaquina, quinino e tetraciclina: efeitos antiproliferativos de antimaláricos relevantes em Neospora caninum

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

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