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1.
Biomed Res Int ; 2021: 8821318, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33732744

RESUMEN

The off-label use of antiviral and antimalarial drugs has been considered by many researchers as a fast and relatively safe alternative to provide therapeutic options to treat COVID-19, but the assessment of such drug-specific effectiveness in this regard is far from complete. Especially, the current body of knowledge about COVID-19 therapeutics needs more data regarding drug effectiveness and safety in the severely ill patients with comorbidities. In the present article, we retrospectively analyze data from 61 patients that received treatment with chloroquine, lopinavir/ritonavir, both drugs administered together, or a standard treatment with no antiviral drugs, and the study was carried in severely ill patients. We found that either drug is ineffective at treating COVID-19, as they are not able to reduce hospitalization length, mortality, C-reactive protein (CRP), lactate dehydrogenase (LDH), d-Dimer, or ferritin, or to enhance gasometric parameters, lymphocytes, total leukocytes, and neutrophil levels, whereas both drugs administered together decrease circulating lymphocytes, increase LDH and ferritin levels, and more importantly, enhance mortality. In this way, our results show that both drugs are ineffective and even potentially harmful alternatives against SARS-CoV-2.


Asunto(s)
/tratamiento farmacológico , Cloroquina/efectos adversos , Cloroquina/uso terapéutico , Lopinavir/efectos adversos , Lopinavir/uso terapéutico , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antimaláricos/efectos adversos , Antimaláricos/uso terapéutico , Antivirales/efectos adversos , Antivirales/uso terapéutico , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto Joven
2.
Scand J Trauma Resusc Emerg Med ; 29(1): 48, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33722251

RESUMEN

BACKGROUND: Chloroquine use has increased worldwide recently in the setting of experimental treatment for the novel coronavirus disease (Covid-19). Nevertheless, in case of chloroquine intoxication, it can be life threatening, with cardiac arrest, due to its cardiac toxicity. CASE PRESENTATION: This case study reports on a 14-years-old girl who presented in cardiac arrest after an uncommon suicide attempt by ingesting 3 g of chloroquine. After 66 min of cardio-pulmonary resuscitation (CPR), extracorporeal cardiopulmonary resuscitation (ECPR) was initiated, allowing cardiac function to recover. CONCLUSIONS: Chloroquine intoxication is a rare but serious condition due to its cardiac toxicity. Use of ECPR in this case of transient toxicity allowed a favorable evolution with little neurological impairment.


Asunto(s)
/tratamiento farmacológico , Reanimación Cardiopulmonar/métodos , Cloroquina/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Paro Cardíaco/terapia , Adolescente , Antimaláricos/efectos adversos , Antimaláricos/uso terapéutico , Cloroquina/uso terapéutico , Femenino , Paro Cardíaco/inducido químicamente , Humanos , Pandemias , Índice de Severidad de la Enfermedad
3.
PLoS One ; 16(3): e0247356, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33667247

RESUMEN

BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZM) are antimalarial drugs recently reported to be active against severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2), which is causing the global COVID-19 pandemic. In an emergency response to the pandemic, we aimed to develop a quantitation method for HCQ, its metabolites desethylhydroxychloroquine (DHCQ) and bisdesethylchloroquine (BDCQ), and AZM in human plasma. METHODS: Liquid chromatography tandem mass spectrometry was used to develop the method. Samples (20 µL) are extracted by solid-phase extraction and injected onto the LC-MS/MS system equipped with a PFP column (2.0 × 50 mm, 3 µm). ESI+ and MRM are used for detection. Ion pairs m/z 336.1→247.1 for HCQ, 308.1→179.1 for DHCQ, 264.1→179.1 for BDCQ, and 749.6→591.6 for AZM are selected for quantification. The ion pairs m/z 342.1→253.1, 314.1→181.1, 270.1→181.1, and 754.6→596.6 are selected for the corresponding deuterated internal standards (IS) HCQ-d4, DHCQ-d4, BDCQ-d4, and AZM-d5. The less abundant IS ions from 37Cl were used to overcome the interference from the analytes. RESULTS: Under optimized conditions, retention times are 0.78 min for BDCQ, 0.79 min for DHCQ, 0.92 min for HCQ and 1.87 min for AZM. Total run time is 3.5 min per sample. The calibration ranges are 2-1000 ng/mL for HCQ and AZM, 1-500 ng/mL for DHCQ and 0.5-250 ng/mL for BDCQ; samples above the range are validated for up to 10-fold dilution. Recoveries of the method ranged from 88.9-94.4% for HCQ, 88.6-92.9% for DHCQ, 88.7-90.9% for BDCQ, and 98.6%-102% for AZM. The IS normalized matrix effect were within (100±10) % for all 4 analytes. Blood samples are stable for at least 6 hr at room temperature. Plasma samples are stable for at least 66 hr at room temperature, 38 days at -70°C, and 4 freeze-thaw cycles. CONCLUSIONS: An LC-MS/MS method for simultaneous quantitation of HCQ, DHCQ, BDCQ, and AZM in human plasma was developed and validated for clinical studies requiring fast turnaround time and small samples volume.


Asunto(s)
Antibacterianos/sangre , Antimaláricos/sangre , Azitromicina/sangre , Cloroquina/análogos & derivados , Hidroxicloroquina/análogos & derivados , Hidroxicloroquina/sangre , Recolección de Muestras de Sangre/métodos , Cloroquina/sangre , Cromatografía Líquida de Alta Presión/métodos , Monitoreo de Drogas/métodos , Ácido Edético/sangre , Humanos , Límite de Detección , Espectrometría de Masas en Tándem/métodos
4.
Zhongguo Zhong Yao Za Zhi ; 46(2): 347-358, 2021 Jan.
Artículo en Chino | MEDLINE | ID: mdl-33645121

RESUMEN

Artemisiae Annuae Herba is a traditional Chinese medicine for clearing deficiency and heat. It is the only natural source of artemisinin, which is a specific antimalarial drug, and has been widely concerned all over the world. In addition to artemisinin, Artemisiae Annuae Herba also contains many sesquiterpenes, coumarins, flavonoids, volatile oils, polysaccharides and other chemical components, which show antipyretic, anti-inflammatory, antiviral microorganisms, anti-asthma, anti-oxidation, anti-tumor and other pharmacological activities. In addition to their own pharmacological activities, some components could enhance the antimalarial activity of artemisinin through different mechanisms at absorption and metabolism in vivo. In order to understand the pharmacokinetic characte-ristics of the chemical constituents contained in Artemisiae Annuae Herba and provide reference for the full development and clinical utilization of Artemisiae Annuae Herba resources in China, this present paper systematically collated the modern research literatures, and summarized the biosynthesis, in vivo analysis and pharmacokinetics of the chemical constituents in Artemisiae Annuae Herba.


Asunto(s)
Antimaláricos , Medicamentos Herbarios Chinos , Aceites Volátiles , China , Medicina China Tradicional
5.
Molecules ; 26(4)2021 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-33673007

RESUMEN

Malaria remains a significant cause of morbidity and mortality in Sub-Saharan Africa and South Asia. While clinical antimalarials are efficacious when administered according to local guidelines, resistance to every class of antimalarials is a persistent problem. There is a constant need for new antimalarial therapeutics that complement parasite control strategies to combat malaria, especially in the tropics. In this work, nopol-based quinoline derivatives were investigated for their inhibitory activity against Plasmodium falciparum, one of the parasites that cause malaria. The nopyl-quinolin-8-yl amides (2-4) were moderately active against the asexual blood stage of chloroquine-sensitive strain Pf3D7 but inactive against chloroquine-resistant strains PfK1 and PfNF54. The nopyl-quinolin-4-yl amides and nopyl-quinolin-4-yl-acetates analogs were generally less active on all three strains. Interesting, the presence of a chloro substituent at C7 of the quinoline ring of amide 8 resulted in sub-micromolar EC50 in the PfK1 strain. However, 8 was more than two orders of magnitude less active against Pf3D7 and PfNF54. Overall, the nopyl-quinolin-8-yl amides appear to share similar antimalarial profile (asexual blood-stage) with previously reported 8-aminoquinolines like primaquine. Future work will focus on investigating the moderately active and selective nopyl-quinolin-8-yl amides on the gametocyte or liver stages of Plasmodium falciparum and Plasmodium vivax.


Asunto(s)
Antimaláricos/farmacología , Compuestos Bicíclicos con Puentes/farmacología , Plasmodium/efectos de los fármacos , Quinolinas/farmacología , Antimaláricos/síntesis química , Antimaláricos/química , Compuestos Bicíclicos con Puentes/síntesis química , Compuestos Bicíclicos con Puentes/química , Células Hep G2 , Humanos , Quinolinas/síntesis química , Quinolinas/química
6.
Rev Bras Parasitol Vet ; 30(1): e022120, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33787719

RESUMEN

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.


Asunto(s)
Antimaláricos , Neospora/efectos de los fármacos , Antimaláricos/farmacología , Atovacuona/farmacología , Cloroquina/farmacología , Primaquina/farmacología , Quinina/farmacología , Tetraciclinas/farmacología
7.
Eur J Pharmacol ; 897: 173928, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33545161

RESUMEN

The recent SARS-CoV-2 pandemic poses one of the greatest challenges to modern medicine. Therefore, identification of new therapeutic strategies seems essential either based on novel vaccines or drugs or simply repurposing existing drugs. Notably, due to their known safety profile, repurposing of existing drugs is the fastest and highly efficient approach to bring a therapeutic to a clinic for any new indication. One such drug that has been used extensively for decades is chloroquine (CQ, with its derivatives) either for malaria, lupus and rheumatoid arthritis. Accumulating body of evidence from experimental pharmacology suggests that CQ and related analogues also activate certain pathways that can potentially be exploited for therapeutic gain. For example, in the airways, this has opened an attractive avenue for developing novel bitter taste ligands as a new class of bronchodilators for asthma. While CQ and its derivatives have been proposed as a therapy in COVID-19, it remains to be seen whether it really work in the clinic? To this end, our perspective aims to provide a timely yet brief insights on the existing literature on CQ and the controversies surrounding its use in COVID-19. Further, we also highlight some of cell-based mechanism(s) that CQ and its derivatives affect in mediating variety of physiological responses in the cell. We believe, data emanating from the clinical studies and continual understanding of the fundamental mechanisms may potentially help in designing effective therapeutic strategies that meets both efficacy and safety criteria for COVID-19.


Asunto(s)
Antimaláricos/uso terapéutico , Autofagia/efectos de los fármacos , Cloroquina/uso terapéutico , Gusto/efectos de los fármacos , Reposicionamiento de Medicamentos , Humanos
8.
Toxicol Lett ; 342: 73-84, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33609687

RESUMEN

Trovafloxacin (TVX) is associated with idiosyncratic drug-induced liver injury (iDILI) and inflammation-mediated hepatotoxicity. However, the inflammatory stress-regulated mechanisms in iDILI remain unclear. Herein, we elucidated the novel role of tumor-necrosis factor alpha (TNFα), an inflammatory stress factor, in TVX-induced in vitro hepatotoxicity and synergistic toxicity. TVX specifically induced synergistic toxicity in HepG2 cells with TNFα, which inhibits autophagy. TVX-treated HepG2 cells induced protective autophagy by inhibiting the expression of mTOR signaling proteins, while ATG5 knockdown in HepG2 cells, responsible for the impairment of autophagy, enhanced TVX-induced toxicity due to the increase in cytochrome C release and JNK pathway activation. Interestingly, the expression of mTOR signal proteins, which were suppressed by TVX, disrupted the negative feedback of the PI3K/AKT pathway and TNFα rebounded p70S6K phosphorylation. Co-treatment with TVX and TNFα inhibited protective autophagy by maintaining p70S6K activity, which enhanced TVX-induced cytotoxicity. Phosphorylation of p70S6K was inhibited by siRNA knockdown and rapamycin to restore TNFα-inhibited autophagy, which prevented the synergistic effect on TVX-induced cytotoxicity. These results indicate that TVX activates protective autophagy in HepG2 cells exposed to toxicity and an imbalance in negative feedback regulation of autophagy by TNFα synergistically enhanced the toxicity. The finding from this study may contribute to a better understanding of the mechanisms underlying iDILI associated with inflammatory stress.


Asunto(s)
Autofagia/efectos de los fármacos , Fluoroquinolonas/toxicidad , Hepatocitos/efectos de los fármacos , Naftiridinas/toxicidad , Factor de Necrosis Tumoral alfa/farmacología , Antimaláricos/toxicidad , Supervivencia Celular , Cloroquina/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Humanos , Levofloxacino/farmacología , MAP Quinasa Quinasa 4/genética , MAP Quinasa Quinasa 4/metabolismo , Piperazinas/toxicidad , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Inhibidores de Captación de Serotonina y Norepinefrina/toxicidad , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Triazoles/toxicidad
9.
Lancet Glob Health ; 9(3): e320-e330, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33607030

RESUMEN

BACKGROUND: The rate of diagnostic testing for malaria is still very low in Nigeria despite the scale-up of malaria rapid diagnostic test (MRDT) availability, following WHO's recommendation of universal diagnostic testing in 2010. We investigated whether a social group sensitisation and education intervention (social group intervention) and a social group intervention plus health-care provider training intervention would increase the demand (use or request, or both) for MRDTs among community members in Ebonyi state, Nigeria. METHODS: We did a three-arm, parallel, open-label, stratified cluster-randomised controlled trial in Ebonyi state, Nigeria, to evaluate the effects of two interventions compared with a control. We randomly assigned geographical clusters that were accessible (close to a road that was drivable even during the rainy seasons) and had at least one eligible public primary health facility and patent medicine vendor (those that offered MRDT services) in a 1:1:1 allocation to the control arm (receiving no intervention), social group arm (receiving sensitisation and education about MRDT), or social group plus provider arm (receiving the social group intervention plus provider training in health communication about MRDT). Investigators, participants (social groups, providers, respondents), and interviewers could not be masked to group assignments. The primary outcome was the proportion of children younger than 5 years with fever or malaria-like illness, in the 2 weeks preceding a household survey, who received an MRDT, and the coprimary outcome was the same outcome but among children aged 5 years and older (ie, up to and including 17 years) and adults (excluding pregnant women). The outcomes were measured at an individual level via household surveys before the interventions and 3 months after the end of the interventions. All analyses were done using a cluster-level method on an intention-to-treat basis. This trial is registered with ISRCTN, number ISRCTN14046444. FINDINGS: We carried out eligibility screening and recruitment of participants (clusters, social groups, and providers) between July 2 and Sept 27, 2018. 34 clusters met the eligibility criteria and 18 were randomly selected to participate and randomly assigned to arms (six clusters per arm). A mean proportion of 40·6% (SD 14·5) of eligible children younger than 5 years in the control arm received an MRDT, versus 66·7% (11·7) in the social group arm (adjusted risk difference [aRD] 28·8%, 95% CI 21·9-35·7, p<0·0001) and 71·7% (19·8) in the social group plus provider arm (aRD 32·7%, 24·9-40·5, p<0·0001), with no significant difference between the social group arm and the social group plus provider arm. A mean proportion of 36·3% (18·5) of eligible children aged 5 years and older in the control arm received an MRDT, versus 60·7% (14·0) in the social group arm (aRD 25·6%, 16·8-34·4, p=0·0004), and 59·5% (18·3) in the social group plus provider arm (aRD 28·0%, 19·5-36·5, p=0·0002), with no significant difference between the social group arm and the social group plus provider arm. INTERPRETATION: The sensitisation and education of social groups about MRDTs can significantly increase the demand for MRDTs. This intervention is pragmatic and could be applied within malaria control or elimination programmes, in Nigeria and in other high-burden countries, to enhance diagnostic testing for patients suspected of having malaria. FUNDING: There was no funding source for this study.


Asunto(s)
Educación en Salud/organización & administración , Personal de Salud/educación , Necesidades y Demandas de Servicios de Salud/organización & administración , Malaria/diagnóstico , Pruebas en el Punto de Atención , Adolescente , Adulto , Antimaláricos , Niño , Preescolar , Femenino , Humanos , Lactante , Capacitación en Servicio/organización & administración , Masculino , Técnicas Microbiológicas , Nigeria , Factores de Tiempo , Adulto Joven
10.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33542018

RESUMEN

We report a case of chronic Q fever presenting with catastrophic bleeding from an infected abdominal aortic aneurysm causing a primary aortoduodenal fistula in an 80-year-old retired farmer. This presentation is rarely reported in literature and only through case reports. Early diagnosis and definitive surgery were critical to a successful outcome. Serological diagnosis of Q fever was initiated on the patient's past exposure to animal reservoirs. Complicating the case was ongoing gastrointestinal bleeding postsurgery, with multiple endoscopies undertaken before a culprit remnant fistula was found. This case highlights the value in considering Coxiella burnetii as an underlying cause in patients with known risk factors presenting with primary aortoduodenal fistulas. Though rare, it represents a readily treatable cause.


Asunto(s)
Aneurisma de la Aorta Abdominal/complicaciones , Hemorragia Gastrointestinal/etiología , Fístula Intestinal/cirugía , Fiebre Q/diagnóstico , Fístula Vascular/cirugía , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Antimaláricos/uso terapéutico , Coxiella burnetii/aislamiento & purificación , Doxiciclina/uso terapéutico , Enfermedades Duodenales/cirugía , Humanos , Hidroxicloroquina/uso terapéutico , Masculino , Fiebre Q/tratamiento farmacológico , Tomografía Computarizada por Rayos X
11.
Cochrane Database Syst Rev ; 2: CD013587, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33624299

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in substantial mortality. Some specialists proposed chloroquine (CQ) and hydroxychloroquine (HCQ) for treating or preventing the disease. The efficacy and safety of these drugs have been assessed in randomized controlled trials. OBJECTIVES: To evaluate the effects of chloroquine (CQ) or hydroxychloroquine (HCQ) for 1) treating people with COVID-19 on death and time to clearance of the virus; 2) preventing infection in people at risk of SARS-CoV-2 exposure; 3) preventing infection in people exposed to SARS-CoV-2. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Current Controlled Trials (www.controlled-trials.com), and the COVID-19-specific resources www.covid-nma.com and covid-19.cochrane.org, for studies of any publication status and in any language. We performed all searches up to 15 September 2020. We contacted researchers to identify unpublished and ongoing studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) testing chloroquine or hydroxychloroquine in people with COVID-19, people at risk of COVID-19 exposure, and people exposed to COVID-19. Adverse events (any, serious, and QT-interval prolongation on electrocardiogram) were also extracted. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility of search results, extracted data from the included studies, and assessed risk of bias using the Cochrane 'Risk of bias' tool. We contacted study authors for clarification and additional data for some studies. We used risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CIs). We performed meta-analysis using a random-effects model for outcomes where pooling of effect estimates was appropriate. MAIN RESULTS: 1. Treatment of COVID-19 disease We included 12 trials involving 8569 participants, all of whom were adults. Studies were from China (4); Brazil, Egypt, Iran, Spain, Taiwan, the UK, and North America (each 1 study); and a global study in 30 countries (1 study). Nine were in hospitalized patients, and three from ambulatory care. Disease severity, prevalence of comorbidities, and use of co-interventions varied substantially between trials. We found potential risks of bias across all domains for several trials. Nine trials compared HCQ with standard care (7779 participants), and one compared HCQ with placebo (491 participants); dosing schedules varied. HCQ makes little or no difference to death due to any cause (RR 1.09, 95% CI 0.99 to 1.19; 8208 participants; 9 trials; high-certainty evidence). A sensitivity analysis using modified intention-to-treat results from three trials did not influence the pooled effect estimate.  HCQ may make little or no difference to the proportion of people having negative PCR for SARS-CoV-2 on respiratory samples at day 14 from enrolment (RR 1.00, 95% CI 0.91 to 1.10; 213 participants; 3 trials; low-certainty evidence). HCQ probably results in little to no difference in progression to mechanical ventilation (RR 1.11, 95% CI 0.91 to 1.37; 4521 participants; 3 trials; moderate-certainty evidence). HCQ probably results in an almost three-fold increased risk of adverse events (RR 2.90, 95% CI 1.49 to 5.64; 1394 participants; 6 trials; moderate-certainty evidence), but may make little or no difference to the risk of serious adverse events (RR 0.82, 95% CI 0.37 to 1.79; 1004 participants; 6 trials; low-certainty evidence). We are very uncertain about the effect of HCQ on time to clinical improvement or risk of prolongation of QT-interval on electrocardiogram (very low-certainty evidence). One trial (22 participants) randomized patients to CQ versus lopinavir/ritonavir, a drug with unknown efficacy against SARS-CoV-2, and did not report any difference for clinical recovery or adverse events. One trial compared HCQ combined with azithromycin against standard care (444 participants). This trial did not detect a difference in death, requirement for mechanical ventilation, length of hospital admission, or serious adverse events. A higher risk of adverse events was reported in the HCQ-and-azithromycin arm; this included QT-interval prolongation, when measured. One trial compared HCQ with febuxostat, another drug with unknown efficacy against SARS-CoV-2 (60 participants). There was no difference detected in risk of hospitalization or change in computed tomography (CT) scan appearance of the lungs; no deaths were reported. 2. Preventing COVID-19 disease in people at risk of exposure to SARS-CoV-2 Ongoing trials are yet to report results for this objective. 3. Preventing COVID-19 disease in people who have been exposed to SARS-CoV-2 One trial (821 participants) compared HCQ with placebo as a prophylactic agent in the USA (around 90% of participants) and Canada. Asymptomatic adults (66% healthcare workers; mean age 40 years; 73% without comorbidity) with a history of exposure to people with confirmed COVID-19 were recruited. We are very uncertain about the effect of HCQ on the primary outcomes, for which few events were reported: 20/821 (2.4%) developed confirmed COVID-19 at 14 days from enrolment, and 2/821 (0.2%) were hospitalized due to COVID-19 (very low-certainty evidence). HCQ probably increases the risk of adverse events compared with placebo (RR 2.39, 95% CI 1.83 to 3.11; 700 participants; 1 trial; moderate-certainty evidence). HCQ may result in little or no difference in serious adverse events (no RR: no participants experienced serious adverse events; low-certainty evidence). One cluster-randomized trial (2525 participants) compared HCQ with standard care for the prevention of COVID-19 in people with a history of exposure to SARS-CoV-2 in Spain. Most participants were working or residing in nursing homes; mean age was 49 years. There was no difference in the risk of symptomatic confirmed COVID-19 or production of antibodies to SARS-CoV-2 between the two study arms. AUTHORS' CONCLUSIONS: HCQ for people infected with COVID-19 has little or no effect on the risk of death and probably no effect on progression to mechanical ventilation. Adverse events are tripled compared to placebo, but very few serious adverse events were found. No further trials of hydroxychloroquine or chloroquine for treatment should be carried out. These results make it less likely that the drug is effective in protecting people from infection, although this is not excluded entirely. It is probably sensible to complete trials examining prevention of infection, and ensure these are carried out to a high standard to provide unambiguous results.


Asunto(s)
Antimaláricos/uso terapéutico , /prevención & control , Cloroquina/uso terapéutico , Hidroxicloroquina/uso terapéutico , Adulto , Anciano , Antimaláricos/efectos adversos , Antivirales/efectos adversos , Antivirales/uso terapéutico , Sesgo , /mortalidad , Causas de Muerte , Cloroquina/efectos adversos , Humanos , Hidroxicloroquina/efectos adversos , Persona de Mediana Edad , Pandemias , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial/estadística & datos numéricos , Nivel de Atención , Resultado del Tratamiento
12.
Rev Soc Bras Med Trop ; 54: e05362020, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33605379

RESUMEN

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.


Asunto(s)
Antimaláricos , Artemisininas , Malaria Falciparum , Malaria , Antimaláricos/efectos adversos , Arteméter/uso terapéutico , Combinación Arteméter y Lumefantrina/uso terapéutico , Artemisininas/efectos adversos , Combinación de Medicamentos , Electrocardiografía , Humanos , Malaria/tratamiento farmacológico , Malaria Falciparum/tratamiento farmacológico , Quinolinas
13.
BMC Complement Med Ther ; 21(1): 64, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33588819

RESUMEN

BACKGROUND: The disparity of harvesting locations can influence the chemical composition of a plant species, which could affect its quality and bioactivity. Terminalia albida is widely used in traditional Guinean medicine whose activity against malaria has been validated in vitro and in murine models. The present work investigated the antimalarial properties and chemical composition of two samples of T. albida collected from different locations in Guinea. METHOD: T. albida samples were collected in different locations in Guinea, in Dubréka prefecture (West maritime Guinea) and in Kankan prefecture (eastern Guinea). The identity of the samples was confirmed by molecular analysis. In vitro antiplasmodial activity of the two extracts was determined against the chloroquine resistant strain PfK1. In vivo, extracts (100 mg/kg) were tested in two experimental murine models, respectively infected with P. chabaudi chabaudi and P. berghei ANKA. The chemical composition of the two samples was assessed by ultra-high-performance liquid chromatography coupled to high resolution mass spectrometry. RESULTS: In vitro, the Dubréka sample (TaD) was more active with an IC50 of 1.5 µg/mL versus 8.5 µg/mL for the extract from Kankan (TaK). In vivo, the antiparasitic effect of TaD was substantial with 56% of parasite inhibition at Day 10 post-infection in P. chabaudi infection and 61% at Day 8 in P. berghei model, compared to 14 and 19% inhibition respectively for the treatment with TaK. In addition, treatment with TaD further improved the survival of P. berghei infected-mice by 50% at Day 20, while the mortality rate of mice treated with Tak was similar to the untreated group. The LC/MS analysis of the two extracts identified 38 compounds, 15 of which were common to both samples while 9 and 14 other compounds were unique to TaD and TaK respectively. CONCLUSION: This study highlights the variability in the chemical composition of the species T. albida when collected in different geographical locations. These chemical disparities were associated with variable antimalarial effects. From a public health perspective, these results underline the importance of defining chemical fingerprints related to botanical species identification and to biological activity, for the plants most commonly used in traditional medicine.


Asunto(s)
Antimaláricos/química , Malaria/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/química , Plasmodium/efectos de los fármacos , Terminalia/química , Animales , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Femenino , Guinea , Malaria/parasitología , Masculino , Medicina Tradicional Africana , Ratones Endogámicos C57BL , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Especificidad de la Especie , Terminalia/clasificación
14.
BMC Complement Med Ther ; 21(1): 71, 2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33607987

RESUMEN

BACKGROUND: In previous studies, Cassia spectabilis DC leaf has shown a good antiplasmodial activity. Therefore, this study is a follow-up study of the extract of leaf of C. spectabilis DC on its in vitro and in vivo antiplasmodial activity and mechanism as an antimalarial. METHODS: The extract was fractionated, sub-fractionated and isolated to obtain the purified compound. In vitro antiplasmodial activity test against Plasmodium falciparum to find out the active compound. In vivo test against P. berghei ANKA-infected mice was conducted to determine prophylactic activity and antiplasmodial activity either alone or in combination with artesunate. The inhibition of heme detoxification test as one of the antimalarial mechanisms was carried out using the Basilico method. RESULTS: The results showed that active antimalarial compound isolated from C. spectabilis DC leaf had a structural pattern that was identical to (-)-7-hydroxycassine. Prophylactic test of 90% ethanolic extract of C. spectabilis DC leaf alone against P. berghei ANKA-infected mice obtained the highest percentage inhibition was 68.61%, while positive control (doxycycline 13 mg/kg) was 73.54%. In combination with artesunate, 150 mg/kg three times a day of C. spectabilis DC (D0-D2) + artesunate (D2) was better than the standard combination of amodiaquine + artesunate where the inhibition percentages were 99.18 and 92.88%, respectively. The IC50 of the extract for the inhibitory activity of heme detoxification was 0.375 mg/ml which was better than chloroquine diphosphate (0.682 mg/ml). CONCLUSION: C. spectabilis DC leaf possessed potent antiplasmodial activity and may offer a potential agent for effective and affordable antimalarial phytomedicine.


Asunto(s)
Antimaláricos/farmacología , Cassia/química , Hemo/metabolismo , Malaria/parasitología , Extractos Vegetales/farmacología , Plasmodium berghei/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/aislamiento & purificación , Antimaláricos/uso terapéutico , Artesunato/uso terapéutico , Cloroquina/análogos & derivados , Cloroquina/farmacología , Cetonas , Malaria/tratamiento farmacológico , Masculino , Ratones Endogámicos BALB C , Fitoterapia , Piperidinas , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Plasmodium berghei/metabolismo , Plasmodium falciparum/metabolismo
15.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33542005

RESUMEN

Acute cerebellar ataxia is a rare primary manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE). We report a case of a 22-year-old woman who presented with gait instability, behavioural changes and new-onset seizures. The tempo of disease progression was explained by an autoimmune cause, eventually fulfilling the criteria for systemic lupus erythematosus. The patient's neurological symptoms improved markedly following administration of steroids and immunomodulators. A review of literature on cerebellar ataxia in NPSLE and a summary of all reported cases to date are also presented.


Asunto(s)
Antiinflamatorios/uso terapéutico , Ataxia Cerebelosa/etiología , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Vasculitis por Lupus del Sistema Nervioso Central/tratamiento farmacológico , Prednisona/uso terapéutico , Adulto , Antimaláricos/uso terapéutico , Femenino , Análisis de la Marcha , Cefalea/etiología , Humanos , Hidroxicloroquina/uso terapéutico , Vasculitis por Lupus del Sistema Nervioso Central/complicaciones , Convulsiones/etiología
16.
Chemistry ; 27(17): 5555-5563, 2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482050

RESUMEN

The total synthesis of dehydroantofine was achieved by employing a novel, regioselective, azahetero Diels-Alder reaction of easily accessible 3,5-dichloro-2H-1,4-oxazin-2-one with 14 a as a key step. Furthermore, it is demonstrated that dehydroantofine is a promising candidate as a new antimalarial agent in a biological assay with chloroquine-resistant Plasmodium falciparum.


Asunto(s)
Antimaláricos , Antimaláricos/farmacología , Cloroquina/farmacología , Resistencia a Medicamentos , Plasmodium falciparum
17.
Artículo en Inglés | MEDLINE | ID: mdl-33478166

RESUMEN

CONTEXT: In Mali, malaria transmission is seasonal, exposing children to high morbidity and mortality. A preventative strategy called Seasonal Malaria Chemoprevention (SMC) is being implemented, consisting of the distribution of drugs at monthly intervals for up to 4 months to children between 3 and 59 months of age during the period of the year when malaria is most prevalent. This study aimed to analyze the evolution of the incidence of malaria in the general population of the health districts of Kati, Kadiolo, Sikasso, Yorosso, and Tominian in the context of SMC implementation. METHODS: This is a transversal study analyzing the routine malaria data and meteorological data of Nasa Giovanni from 2016 to 2018. General Additive Model (GAM) analysis was performed to investigate the relationship between malaria incidence and meteorological factors. RESULTS: From 2016 to 2018, the evolution of the overall incidence in all the study districts was positively associated with the relative humidity, rainfall, and minimum temperature components. The average monthly incidence and the relative humidity varied according to the health district, and the average temperature and rainfall were similar. A decrease in incidence was observed in children under five years old in 2017 and 2018 compared to 2016. CONCLUSION: A decrease in the incidence of malaria was observed after the SMC rounds. SMC should be applied at optimal periods.


Asunto(s)
Antimaláricos , Malaria , Antimaláricos/uso terapéutico , Quimioprevención , Niño , Preescolar , Humanos , Incidencia , Malaria/epidemiología , Malaria/prevención & control , Malí/epidemiología , Estaciones del Año
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