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1.
Mem Inst Oswaldo Cruz ; 115: e200229, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33053077

RESUMEN

Malaria and tuberculosis are no longer considered to be neglected diseases by the World Health Organization. However, both are huge challenges and public health problems in the world, which affect poor people, today referred to as neglected populations. In addition, malaria and tuberculosis present the same difficulties regarding the treatment, such as toxicity and the microbial resistance. The increase of Plasmodium resistance to the available drugs along with the insurgence of multidrug- and particularly tuberculosis drug-resistant strains are enough to justify efforts towards the development of novel medicines for both diseases. This literature review provides an overview of the state of the art of antimalarial and antituberculosis chemotherapies, emphasising novel drugs introduced in the pharmaceutical market and the advances in research of new candidates for these diseases, and including some aspects of their mechanism/sites of action.


Asunto(s)
Antimaláricos/uso terapéutico , Antituberculosos/uso terapéutico , Malaria/tratamiento farmacológico , Tuberculosis/tratamiento farmacológico , Humanos , Malaria/diagnóstico , Enfermedades Desatendidas , Tuberculosis/diagnóstico
2.
Lancet Child Adolesc Health ; 4(10): 761-774, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32946830

RESUMEN

All malaria infections are harmful to both the pregnant mother and the developing fetus. One in ten maternal deaths in malaria endemic countries are estimated to result from Plasmodium falciparum infection. Malaria is associated with a 3-4 times increased risk of miscarriage and a substantially increased risk of stillbirth. Current treatment and prevention strategies reduce, but do not eliminate, malaria's damaging effects on pregnancy outcomes. Reviewing evidence generated from meta-analyses, systematic reviews, and observational data, the first paper in this Series aims to summarise the adverse effects of malaria in pregnancy on the fetus and how the current drug treatment and prevention strategies can alleviate these effects. Although evidence supports the safety and treatment efficacy of artemisinin-based combination therapies in the first trimester, these therapies have not been recommended by WHO for the treatment of malaria at this stage of pregnancy. Intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine is contraindicated in the first trimester and provides imperfect chemoprevention because of inadequate dosing, poor (few and late) antenatal clinic attendance, increasing antimalarial drug resistance, and decreasing naturally acquired maternal immunity due to the decreased incidence of malaria. Alternative strategies to prevent malaria in pregnancy are needed. The prevention of all malaria infections by providing sustained exposure to effective concentrations of antimalarial drugs is key to reducing the adverse effects of malaria in pregnancy.


Asunto(s)
Antimaláricos/uso terapéutico , Malaria/tratamiento farmacológico , Complicaciones Parasitarias del Embarazo/tratamiento farmacológico , Pirimetamina/uso terapéutico , Sulfadoxina/uso terapéutico , Anomalías Inducidas por Medicamentos/prevención & control , Antimaláricos/efectos adversos , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Malaria/prevención & control , Estudios Observacionales como Asunto , Embarazo , Pirimetamina/efectos adversos , Sulfadoxina/efectos adversos , Revisiones Sistemáticas como Asunto
3.
Lancet Child Adolesc Health ; 4(10): 775-789, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32946831

RESUMEN

Malaria disproportionately affects children younger than 5 years. Falciparum malaria is responsible for more than 200 000 child deaths per year in Africa and vivax malaria is well documented as a cause of severe anaemia and excess mortality in children in Asia and Oceania. For the treatment of malaria in children, paediatric dosing recommendations for several agents, including parenteral artesunate and dihydroartemisinin-piperaquine, have belatedly been shown to be suboptimal. Worsening antimalarial resistance in Plasmodium falciparum in the Greater Mekong Subregion threatens to undermine global efforts to control malaria. Triple antimalarial combination therapies are being evaluated to try to impede this threat. The RTS,S/AS01 vaccine gives partial protection against falciparum malaria and is being evaluated in large, pilot studies in Ghana, Malawi, and Kenya as a complementary tool to other preventive measures. Seasonal malaria chemoprevention in west Africa has resulted in declines in malaria incidence and deaths and there is interest in scaling up efforts by expanding the age range of eligible recipients. Preventing relapse in Plasmodium vivax infection with primaquine is challenging because treating children who have G6PD deficiency with primaquine can cause acute haemolytic anaemia. The safety of escalating dose regimens for primaquine is being studied to mitigate this risk.


Asunto(s)
Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Bienestar del Niño/estadística & datos numéricos , Vacunas contra la Malaria/uso terapéutico , Malaria/tratamiento farmacológico , Malaria/prevención & control , Niño , Relación Dosis-Respuesta a Droga , Resistencia a Múltiples Medicamentos , Femenino , Humanos , Malaria/epidemiología , Masculino , Estaciones del Año , Vacunación/estadística & datos numéricos
4.
PLoS Med ; 17(9): e1003254, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32925906

RESUMEN

BACKGROUND: Appropriate clinical management of malaria in children is critical for preventing progression to severe disease and for reducing the continued high burden of malaria mortality. This study aimed to assess the quality of care provided to children under 5 diagnosed with malaria across 9 sub-Saharan African countries. METHODS AND FINDINGS: We used data from the Service Provision Assessment (SPA) survey. SPAs are nationally representative facility surveys capturing quality of sick-child care, facility readiness, and provider and patient characteristics. The data set contained 24,756 direct clinical observations of outpatient sick-child visits across 9 countries, including Uganda (2007), Rwanda (2007), Namibia (2009), Kenya (2010), Malawi (2013), Senegal (2013-2017), Ethiopia (2014), Tanzania (2015), and Democratic Republic of the Congo (2018). We assessed the proportion of children with a malaria diagnosis who received a blood test diagnosis and an appropriate antimalarial. We used multilevel logistic regression to assess facility and provider and patient characteristics associated with these outcomes. Subgroup analyses with the 2013-2018 country surveys only were conducted for all outcomes. Children observed were on average 20.5 months old and were most commonly diagnosed with respiratory infection (47.7%), malaria (29.7%), and/or gastrointestinal infection (19.7%). Among the 7,340 children with a malaria diagnosis, 32.5% (95% CI: 30.3%-34.7%) received both a blood-test-based diagnosis and an appropriate antimalarial. The proportion of children with a blood test diagnosis and an appropriate antimalarial ranged from 3.4% to 57.1% across countries. In the more recent surveys (2013-2018), 40.7% (95% CI: 37.7%-43.6%) of children with a malaria diagnosis received both a blood test diagnosis and appropriate antimalarial. Roughly 20% of children diagnosed with malaria received no antimalarial at all, and nearly 10% received oral artemisinin monotherapy, which is not recommended because of concerns regarding parasite resistance. Receipt of a blood test diagnosis and appropriate antimalarial was positively correlated with being seen at a facility with diagnostic equipment in stock (adjusted OR 3.67; 95% CI: 2.72-4.95) and, in the 2013-2018 subsample, with being seen at a facility with Artemisinin Combination Therapies (ACTs) in stock (adjusted OR 1.60; 95% CI:1.04-2.46). However, even if all children diagnosed with malaria were seen by a trained provider at a facility with diagnostics and medicines in stock, only a predicted 37.2% (95% CI: 34.2%-40.1%) would have received a blood test and appropriate antimalarial (44.4% for the 2013-2018 subsample). Study limitations include the lack of confirmed malaria test results for most survey years, the inability to distinguish between a diagnosis of uncomplicated or severe malaria, the absence of other relevant indicators of quality of care including dosing and examinations, and that only 9 countries were studied. CONCLUSIONS: In this study, we found that a majority of children diagnosed with malaria across the 9 surveyed sub-Saharan African countries did not receive recommended care. Clinical management is positively correlated with the stocking of essential commodities and is somewhat improved in more recent years, but important quality gaps remain in the countries studied. Continued reductions in malaria mortality will require a bigger push toward quality improvements in clinical care.


Asunto(s)
Prestación de Atención de Salud/métodos , Malaria/tratamiento farmacológico , Calidad de la Atención de Salud/tendencias , África del Sur del Sahara/epidemiología , Antimaláricos/uso terapéutico , Niño , Preescolar , Estudios Transversales , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Femenino , Humanos , Lactante , Masculino
5.
PLoS Med ; 17(9): e1003318, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32956354

RESUMEN

BACKGROUND: Low-density (LD) Plasmodium infections are missed by standard malaria rapid diagnostic tests (standard mRDT) when the blood antigen concentration is below the detection threshold. The clinical impact of these LD infections is unknown. This study investigates the clinical presentation and outcome of untreated febrile children with LD infections attending primary care facilities in a moderately endemic area of Tanzania. METHODS/FINDINGS: This cohort study includes 2,801 febrile pediatric outpatients (median age 13.5 months [range 2-59], female:male ratio 0.8:1.0) recruited in Dar es Salaam, Tanzania between 01 December 2014 and 28 February 2016. Treatment decisions were guided by a clinical decision support algorithm run on a mobile app, which also collected clinical data. Only standard mRDT+ cases received antimalarials. Outcomes (clinical failure, secondary hospitalization, and death) were collected in follow-up visits or interviews on days 3, 7, and 28. After patient recruitment had ended, frozen blood from all 2,801 patients was tested for Plasmodium falciparum (Pf) by ultrasensitive-quantitative polymerase chain reaction (qPCR), standard mRDT, and "ultrasensitive" mRDT. As the latter did not improve sensitivity beyond standard mRDT, it is hereafter excluded. Clinical features and outcomes in LD patients (standard mRDT-/ultrasensitive-qPCR+, not given antimalarials) were compared with those with no detectable (ND) parasitemia (standard mRDT-/ultrasensitive-qPCR-) or high-density (HD) infections (standard mRDT+/ultrasensitive-qPCR+, antimalarial-treated). Pf positivity rate was 7.1% (n = 199/2,801) and 9.8% (n = 274/2,801) by standard mRDT and ultrasensitive qPCR, respectively. Thus, 28.0% (n = 76/274) of ultrasensitive qPCR+ cases were not detected by standard mRDT and labeled "LD". LD patients were, on average, 10.6 months younger than those with HD infections (95% CI 7.0-14.3 months, p < 0.001). Compared with ND, LD patients more frequently had the diagnosis of undifferentiated fever of presumed viral origin (risk ratio [RR] = 2.0, 95% CI 1.3-3.1, p = 0.003) and were more often suffering from severe malnutrition (RR = 3.2, 95% CI 1.1-7.5, p = 0.03). Despite not receiving antimalarials, outcomes for the LD group did not differ from ND regarding clinical failures (2.6% [n = 2/76] versus 4.0% [n = 101/2,527], RR = 0.7, 95% CI 0.2-3.5, p = 0.7) or secondary hospitalizations (2.6% [n = 2/76] versus 2.8% [n = 72/2,527], RR = 0.7,95% CI 0.2-3.2, p = 0.9), and no deaths were reported in any Pf-positive groups. HD patients experienced more secondary hospitalizations (10.1% [n = 20/198], RR = 0.3, 95% CI 0.1-1.0, p = 0.005) than LD patients. All the patients in this cohort were febrile children; thus, the association between parasitemia and fever cannot be investigated, nor can the conclusions be extrapolated to neonates and adults. CONCLUSIONS: During a 28-day follow-up period, we did not find evidence of a difference in negative outcomes between febrile children with untreated LD Pf parasitemia and those without Pf parasitemia. These findings suggest LD parasitemia may either be a self-resolving fever or an incidental finding in children with other infections, including those of viral origin. These findings do not support a clinical benefit nor additional risk (e.g. because of missed bacterial infections) to using ultrasensitive malaria diagnostics at a primary care level.


Asunto(s)
Parasitemia/diagnóstico , Convulsiones Febriles/etiología , Convulsiones Febriles/parasitología , Antimaláricos/uso terapéutico , Preescolar , Estudios de Cohortes , Femenino , Fiebre/diagnóstico , Humanos , Lactante , Malaria/epidemiología , Malaria Falciparum/tratamiento farmacológico , Masculino , Parasitemia/epidemiología , Plasmodium falciparum/parasitología , Plasmodium falciparum/patogenicidad , Tanzanía/epidemiología
6.
Front Immunol ; 11: 2159, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32983179

RESUMEN

The rapid spread, severity, and lack of specific treatment for COVID-19 resulted in hasty drug repurposing. Conceptually, trials of antivirals were well-accepted, but twentieth century antimalarials sparked an impassioned global debate. Notwithstanding, antiviral and immunomodulatory effects of aminoquinolines have been investigated in vitro, in vivo and in clinical trials for more than 30 years. We review the mechanisms of action of (hydroxy)chloroquine on immune cells and networks and discuss promises and pitfalls in the fight against SARS-CoV-2, the agent of the COVID-19 outbreak.


Asunto(s)
Antimaláricos/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Factores Inmunológicos/uso terapéutico , Inmunomodulación , Neumonía Viral/tratamiento farmacológico , Antimaláricos/efectos adversos , Antimaláricos/farmacología , Antivirales/efectos adversos , Antivirales/farmacología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Reposicionamiento de Medicamentos/métodos , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/farmacología , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/farmacología , Pandemias , Neumonía Viral/inmunología , Neumonía Viral/virología
7.
JAMA Cardiol ; 5(9): 1036-1041, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32936252

RESUMEN

Importance: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. Objective: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. Design, Setting, and Participants: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. Main Outcomes and Measures: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. Results: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. Conclusions and Relevance: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.


Asunto(s)
Azitromicina/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Síndrome de QT Prolongado/epidemiología , Neumonía Viral/tratamiento farmacológico , Anciano , Antibacterianos/uso terapéutico , Antimaláricos/uso terapéutico , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Medición de Riesgo
9.
Medicine (Baltimore) ; 99(36): e22044, 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899064

RESUMEN

BACKGROUND: Malaria remains a global health threat for centuries. In recent years, a rising resistance of Plasmodium falciparum to current standard artemisinin-based combination therapies (ACTs) leads to increasing treatment failures and requires for optimized treatment. Here, we intend to make a systematic review and meta-analysis of optimizing treatment for malaria, so as to find a potential optimal treatment. METHODS: We will search electronic databases: the Cochrane Infectious Diseases Group (CIDG) Specialized Register, the Cochrane Central Register of Controlled Trials (CEN-TRAL), PubMed, Embase, Web of Science from their inception to 1 July, 2020. We will also search International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov, and contact with authors when necessary. Two authors will independently collect and select data, and the statistical analyses will be conducted by Revman V.5.3 software. RESULTS: We will evaluate efficacy and safety of modified ACTs for uncomplicate malaria, comparing with standard ACTs in all eligible clinical studies. CONCLUSION: In this study, we will offer clinical evidence for optimizing treatment for malaria. REGISTRATION NUMBER: INPLASY202070115.


Asunto(s)
Antiinfecciosos/uso terapéutico , Artemisininas/uso terapéutico , Malaria/tratamiento farmacológico , Antimaláricos/uso terapéutico , Terapia Combinada , Femenino , Humanos , Malaria/epidemiología , Malaria/parasitología , Masculino , Plasmodium falciparum/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Seguridad , Insuficiencia del Tratamiento , Resultado del Tratamiento
10.
Curr Opin Rheumatol ; 32(6): 572-582, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32890029

RESUMEN

PURPOSE OF REVIEW: The purpose of this review is highlighting the most recent evidence on the clinical efficacy and toxicity of antimalarials in systemic lupus erythematosus (SLE). RECENT FINDINGS: New data confirm the effects of antimalarials in preventing SLE activity, damage and infections and in decreasing mortality. An important reduction in use of health resources is related to continued antimalarial use. Hydroxychloroquine (HCQ) may prevent preeclampsia in pregnant women with SLE. HCQ ocular toxicity is infrequent and could be associated with blood levels. Gastrointestinal and skin toxicity are underrecognized and could influence adherence. Prolongation of QT interval is extremely unusual with HCQ. Doses of HCQ of 200 mg/day seem to offer a good efficacy/toxicity balance. HCQ protection against herpes zoster and Pneumocystis jirovecii infection has been shown. On the contrary, HCQ prescription by doctors and adherence by patients are both under recommended standards. The recent coronavirus disease 2019 pandemic has resulted in a significant shortage of HCQ in many countries with possible consequences in the correct treatment of lupus patients. SUMMARY: Recent evidence reinforces the central role of HCQ in SLE therapy. The reduction in activity, damage accrual and mortality is consistent across studies, countries and ethnical groups. On the contrary, and despite the well established beneficial effects of prolonged regular HCQ therapy, many SLE patients do never take this drug or it is eventually stopped in the setting of severe flares, pregnancy or presumed toxicity. Every effort must be made to assure the correct prescription of HCQ and not to withdraw the drug unless unequivocal signs of toxicity are present.


Asunto(s)
Antimaláricos/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/epidemiología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Pandemias , Neumonía Viral/epidemiología , Comorbilidad , Infecciones por Coronavirus/tratamiento farmacológico , Femenino , Humanos , Lupus Eritematoso Sistémico/epidemiología , Neumonía Viral/tratamiento farmacológico , Resultado del Tratamiento
11.
BMC Infect Dis ; 20(1): 671, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32933490

RESUMEN

BACKGROUND: The increasing antimalarial drug resistance is a significant hindrance to malaria control and elimination programs. For the last six decades, chloroquine (CQ) plus pyrimethamine remains the first-line treatment for P. vivax malaria. Regions where both P. falciparum and P. vivax co-exist, P. vivax is exposed to antifolate drugs due to either misdiagnosis or improper treatment that causes selective drug pressure to evolve. Therefore, the present study aims to estimate antimalarial drug resistance among the complicated and uncomplicated P. vivax patients. METHODS: A total of 143 P. vivax malaria positive patients were enrolled in this study, and DNA was isolated from their blood samples. Pvcrt-o, Pvmdr-1, Pvdhps, and Pvdhfr genes were PCRs amplified, and drug resistance-associated gene mutations were analyzed. Statistical analysis of the drug resistance genes and population diversity was performed using MEGA vs. 7.0.21 and DnaSP v software. RESULTS: Among the CQ resistance marker gene Pvcrt-o, the prevalence of K10 insertion was 17.5% (7/40) and 9.5% (7/73) of complicated and uncomplicated P vivax group isolates respectively. In Pvmdr-1, double mutant haplotype (M958/L1076) was found in 99% of the clinical isolates. Among the pyrimethamine resistance-associated gene Pvdhfr, the double mutant haplotype I13P33F57R58T61N117I173 was detected in 23% (11/48) in complicated and 20% (17/85) in uncomplicated group isolates. In the sulphadoxine resistance-associated Pvdhps gene, limited polymorphism was observed with the presence of a single mutant (D459A) among 16 and 5% of the clinical isolates in the complicated and uncomplicated group respectively. CONCLUSION: The study presents the situations of polymorphism in the antimalarial drug resistance-associated genes and emphasizes the need for regular surveillance. It is imperative for the development of suitable antimalarial drug policy in India.


Asunto(s)
Antimaláricos/uso terapéutico , Resistencia a Medicamentos/genética , Malaria Vivax/tratamiento farmacológico , Plasmodium vivax/genética , Proteínas Protozoarias/genética , Adolescente , Niño , Preescolar , Cloroquina/uso terapéutico , ADN Protozoario/genética , ADN Protozoario/metabolismo , Femenino , Antagonistas del Ácido Fólico/uso terapéutico , Haplotipos , Humanos , India , Masculino , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Plasmodium vivax/aislamiento & purificación , Polimorfismo de Nucleótido Simple , Adulto Joven
12.
Mikrobiyol Bul ; 54(3): 463-478, 2020 Jul.
Artículo en Turco | MEDLINE | ID: mdl-32755521

RESUMEN

Malaria still remains to be a public health threat and one of the most important infectious diseases to get attention from World Health Organization. No domestic malaria cases have been reported on the island of Cyprus since 1948, as a result of successful elimination process. All of the malaria cases detected in recent years are imported cases. As known, hundreds of medicines are obtained from plants and traditional medicine are used in endemic places of malaria. The cause of malaria - Plasmodium parasites, are developing resistance to antimalarial drugs. Hence, research on plant extracts and essential oils have gained great interest in recent years to obtain new and safe agents/substances. In our study, it was aimed to investigate the in vivo antimalarial activities of essential oils obtained from Origanum dubium, Origanum majorana, Salvia fruticosa and Laurus nobilis plants which grows in Northern Cyprus against Plasmodium berghei - the rodent malaria agent. Plants were collected in appropriate seasons and were dried to obtain and analyze essential oils via Clevenger Apparatus system. L929 mouse fibroblast cell line and MTT [3-(4.5-dimethylthiazole-2-yl) -2.5-diphenyltetrazolium bromide] kit were used to determine the cytotoxic activities of the essential oils obtained. In our study, total of 36 mice (Balb/c) of 6 groups (6 mice in each group) were formed: chloroquine group (CG) (50 mg/kg) as malaria reference group, untreated control group (UTCG), O.dubium (OD) (20 mg/kg), O.majorana (OM) (20 mg/kg), S.fruticosa (SF) (20 mg/kg) and L.nobilis (LN) (20 mg/kg). The essential oils were given to mice infected with P.berghei strain orally on 0, 1, 2 and 3rd days (4 times in total). Blood was taken from the tail end of each mouse 24 hours after the last treatment and blood collection was continued every two days until the mice died. Withdrawn blood taken from the mice were prepared as a thin smear and stained with Giemsa. Then, parasitemia percentages in each smear were calculated. As a result of the cytotoxicity tests, cytotoxic activity was not found at 100 µg/ml (20 mg/kg) in all oils except OD essential oil. While the mice receiving chloroquine continued their lives with the disappearance of the parasite on the 6thday, the mice in the UTCG died on the 9th day. The parasitemia rate reached 35% in the OM group on the 23rd day, in the OD group on the 21st day and in the other groups (SF and LN) on the 14th day and the mice have died. In our study, the difference between the life span in all groups was found statistically significant (p≤ 0.001). As a result, the essential oils O.majorana (14 days increase according to UTCG) an endemic plant of Cyprus and O.dubium (12 days increase according to UTCG) which had an antimalarial effect, decreased parasitemia and increased the life span of mice more than two times, indicated that they could be a source for the acquisition of new antimalarial molecules.


Asunto(s)
Antimaláricos , Malaria , Aceites Volátiles , Origanum , Extractos Vegetales , Animales , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Chipre , Células Nutrientes , Malaria/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Origanum/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Plasmodium berghei/efectos de los fármacos
13.
Ned Tijdschr Geneeskd ; 1642020 06 02.
Artículo en Holandés | MEDLINE | ID: mdl-32749808

RESUMEN

On 3 March 2020, the document 'Drug treatment options for patients with COVID-19 (infections with SARS-CoV-2)' was published on the website of the Dutch Working Party on Antibiotic Policy (StichtingWerkgroepAntibioticabeleid, SWAB). Based on a 7-step analysis of the literature, hydroxychloroquine (HCQ) and chloroquine (CQ) were initially included in the SWAB document as possible drug treatments for hospitalised adult COVID-19 patients. However, recent weeks have seen the publication of the results of various studies into the effectiveness of treatment with HCQ and CQ in patients with COVID-19. On the basis of these results, we conclude that there is insufficient evidence to consider HCQ and CQ as meaningful treatment options in patients with COVID-19. Clinically relevant QTc prolongation occurs in at least 1 in 10 COVID-19 patients treated with HCQ or HQ.


Asunto(s)
Betacoronavirus , Cloroquina/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adulto , Antimaláricos/uso terapéutico , Antivirales/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Humanos , Pandemias
14.
Front Immunol ; 11: 1708, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32754163

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the "cytokine storm" may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients.


Asunto(s)
Betacoronavirus/inmunología , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/inmunología , Interleucina-6/metabolismo , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/inmunología , Corticoesteroides/uso terapéutico , Animales , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antimaláricos/uso terapéutico , Artesunato/uso terapéutico , Infecciones por Coronavirus/virología , Hemoperfusión/métodos , Humanos , Hidroxicloroquina/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Interleucina-6/antagonistas & inhibidores , Ratones , Pandemias , Neumonía Viral/virología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores
16.
PLoS One ; 15(8): e0237693, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32790733

RESUMEN

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antimaláricos/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/farmacología , Azitromicina/uso terapéutico , Niño , Preescolar , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/virología , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Lactante , Recién Nacido , Unidades de Cuidados Intensivos , Interleucina-6/antagonistas & inhibidores , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/mortalidad , Neumonía Viral/virología , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
17.
Malawi Med J ; 32(1): 45-51, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32733659

RESUMEN

Background: Intermittent presumptive treatment in pregnancy (IPTp) of malaria using sulfadoxine-pyrimethamine (SP) was introduced in Nigeria in 2005 to reduce the burden of malaria in pregnancy. By 2013, 23% of reproductive aged women surveyed received SP for malaria prevention in their last pregnancy of the past 5 years. This paper highlights geographic and socio-economic variations and inequities in accessing and using SP for malaria prophylaxis in pregnancy in Nigeria, as well as client-related and service delivery determinants. Methods: Secondary data from 2013 Nigeria demographic and health survey (DHS) was used. Sample of 38,948 eligible women were selected for interview using stratified three-stage cluster design. Data obtained from the individual recode dataset was used for descriptive and logistic regression analysis of factors associated with SP use in pregnancy was performed. Independent variables were age, media exposure, region, place of residence, wealth index, place of antenatal care (ANC) attendance and number of visits. Results: Women in the upper three wealth quintiles were 1.33 - 1.80 times more likely to receive SP than the poorest (CI: 1.15-1.56; 1.41-1.97; 1.49-2.17). Women who received ANC from public health facilities were twice as likely (inverse of OR 0.68) to use SP in pregnancy than those who used private facilities (CI: 0.60-0.76). Those who attended at least 4 ANC visits were 1.46 times more likely to get SP prophylaxis (CI: 1.31-1.63). Using the unadjusted odds ratio, women residing in rural areas were 0.86 times less likely to use SP compared to those in urban areas. Conclusions: Inequities in access to and use of SP for malaria prophylaxis in pregnancy exist across sub-population groups in Nigeria. Targeted interventions on the least covered are needed to reduce existing inequities and scale-up IPTp of malaria.


Asunto(s)
Antimaláricos/administración & dosificación , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Disparidades en Atención de Salud , Malaria/prevención & control , Complicaciones Parasitarias del Embarazo/prevención & control , Atención Prenatal/estadística & datos numéricos , Pirimetamina/administración & dosificación , Sulfadoxina/administración & dosificación , Adolescente , Adulto , Antimaláricos/uso terapéutico , Combinación de Medicamentos , Femenino , Encuestas de Atención de la Salud , Humanos , Persona de Mediana Edad , Nigeria , Aceptación de la Atención de Salud/estadística & datos numéricos , Embarazo , Complicaciones Parasitarias del Embarazo/tratamiento farmacológico , Pirimetamina/uso terapéutico , Sulfadoxina/uso terapéutico , Adulto Joven
18.
Open Heart ; 7(2)2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32817375

RESUMEN

The outbreak of COVID-19 in Wuhan, China and its declaration as a global pandemic by WHO has left the medical community under significant pressure to rapidly identify effective therapeutic and preventative strategies. Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were found to be efficacious against SARS-CoV-2 when investigated in preliminary in vitro experiments. Reports of success in early clinical studies were widely publicised by news outlets, politicians and on social media. These results led several countries to approve the use of these drugs for the treatment of patients with COVID-19. Despite having reasonable safety profiles in the treatment of malaria and certain autoimmune conditions, both drugs are known to have potential cardiotoxic side effects. There is a high incidence of myocardial injury and arrhythmia reported with COVID-19 infection, and as such this population may be more susceptible to this side-effect profile. Studies to date have now demonstrated that in patients with COVID-19, these drugs are associated with significant QTc prolongation, as well as reports of ventricular arrhythmias. Furthermore, subsequent studies have failed to demonstrate clinical benefit from either drug. Indeed, clinical trials have also been stopped early due to safety concerns over HCQ. There is an urgent need for credible solutions to the global pandemic, but we argue that in the absence of high-quality evidence, there needs to be greater caution over the routine use or authorisation of drugs for which efficacy and safety is unproven.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Electrocardiografía/efectos de los fármacos , Síndrome de QT Prolongado/inducido químicamente , Neumonía Viral/tratamiento farmacológico , Medición de Riesgo , Antimaláricos/efectos adversos , Antimaláricos/uso terapéutico , Infecciones por Coronavirus/epidemiología , Salud Global , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Incidencia , Síndrome de QT Prolongado/fisiopatología , Pandemias , Neumonía Viral/epidemiología
19.
Nephrol Dial Transplant ; 35(8): 1346-1353, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32844224

RESUMEN

BACKGROUND: Haemodialysis patients are at risk of developing severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: coronavirus disease 2019 (COVID-19). In March 2020, hydroxychloroquine (HCQ) and azithromycin (AZI) were proposed as potential treatments of COVID-19, but with warnings concerning their possible toxicity. No data are available regarding the toxicity of this treatment in haemodialysis patients. METHODS: We report the use of HCQ and AZI in a cohort of COVID-19 haemodialysis patients with focus on safety concerns. RESULTS: Twenty-one patients received 200 mg HCQ thrice daily during 10 days, and AZI 500 mg on Day 1, and 250 mg on the four following days. HCQ plasma concentrations were within the recommended range (0.1-1.0 µg/mL) in all patients except one, in which maximum concentration was 1.1 µg/mL. HCQ concentration raised until the third day and remained stable thereafter. No cardiac event occurred in spite of progressive lengthening of corrected QT interval (QTc) during the treatment. One patient experienced a long QTc syndrome (QTc >500 ms) without any arrhythmia episode, although HCQ concentration was in the target range. Five (23.8%) patients experienced hypoglycaemia, a well-known HCQ side-effect. SARS-CoV-2 RNA remained detectable in nasopharyngeal swabs for a long time in haemodialysis patients (mean time 21 days). CONCLUSIONS: HCQ and AZI are safe in haemodialysis patients at these doses but can lead to long QTc syndrome and hypoglycaemia. HCQ concentrations were not correlated with side effects. We recommend monitoring of the QTc length throughout treatment, as well as glycaemia. SARS-CoV-2 could persist for longer in haemodialysis patients than in the general population.


Asunto(s)
Azitromicina/uso terapéutico , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Tolerancia a Medicamentos , Hidroxicloroquina/uso terapéutico , Fallo Renal Crónico/terapia , Neumonía Viral/tratamiento farmacológico , Diálisis Renal/métodos , Anciano , Antibacterianos/uso terapéutico , Antimaláricos/uso terapéutico , Comorbilidad , Infecciones por Coronavirus/epidemiología , Femenino , Francia/epidemiología , Humanos , Fallo Renal Crónico/epidemiología , Masculino , Pandemias , Neumonía Viral/epidemiología
20.
Int J Antimicrob Agents ; 56(4): 106144, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32853673

RESUMEN

Hydroxychloroquine (HCQ) has been largely used and investigated as therapy for COVID-19 across various settings at a total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use of low-dose HCQ (total 2400 mg over 5 days) was recommended for hospitalised patients with COVID-19. We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19 hospital surveillance data. Patients treated either with HCQ monotherapy and supportive care (HCQ group) were compared with patients treated with supportive care only (no-HCQ group) using a competing risks proportional hazards regression with discharge alive as competing risk, adjusted for demographic and clinical features with robust standard errors. Of 8075 patients with complete discharge data on 24 May 2020 and diagnosed before 1 May 2020, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the multivariable analysis, mortality was lower in the HCQ group compared with the no-HCQ group [adjusted hazard ratio (aHR) = 0.684, 95% confidence interval (CI) 0.617-0.758]. Compared with the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤5 days (n = 3975) and >5 days (n = 3487) after symptom onset [aHR = 0.701 (95% CI 0.617-0.796) and aHR = 0.647 (95% CI 0.525-0.797), respectively]. Compared with supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalised patients with COVID-19 diagnosed and treated early or later after symptom onset.


Asunto(s)
Antimaláricos/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus/patogenicidad , Proteína C-Reactiva/metabolismo , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/patología , Progresión de la Enfermedad , Cálculo de Dosificación de Drogas , Reposicionamiento de Medicamentos , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Pandemias , Seguridad del Paciente , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/mortalidad , Neumonía Viral/patología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Linfocitos T/patología , Linfocitos T/virología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
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