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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(12): 1182-1187, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31874656

RESUMO

OBJECTIVE: To study the bacteriologic profile and drug resistance of respiratory infection in children, and to provide a basis for etiological diagnosis and rational use of antimicrobial agents. METHODS: A retrospective analysis was performed for 15 047 children who attended the hospital due to respiratory infection from January 2016 to December 2018. Their sputum samples were collected, and the Phoenix-100 automatic microbial identification system was used for the identification and drug sensitivity analysis of the isolated pathogenic bacteria. RESULTS: Of all 17 174 sputum samples detected, there were 2 395 positive samples, with a positive rate of 13.95%; a total of 2 584 strains of pathogenic bacteria were isolated, among which there were 1 577 (61.03%) Gram-negative strains, 967 (37.42%) Gram-positive strains, and 40 (1.55%) fungal strains. The most common pathogen was Haemophilus influenzae (33.90%), followed by Streptococcus pneumoniae (33.55%), Moraxella catarrhalis (19.20%), and Staphylococcus aureus (3.64%). Among the 2 331 children with positive infection, 251 had mixed infection, most commonly with Haemophilus influenzae and Streptococcus pneumoniae. The detection rate of pathogenic bacteria was higher in winter and spring and lower in summer and autumn. There was a significant difference in the detection rate of pathogenic bacteria between different age groups (P<0.05), with the highest detection rate in infants aged 1 month to <1 year. Streptococcus pneumoniae and Staphylococcus aureus had a sensitivity rate of 100% to vancomycin, linezolid, and teicoplanin, and Haemophilus influenzae had a lower sensitivity rate to ampicillin, compound sulfamethoxazole and cefuroxime and a higher sensitivity rate to other drugs. CONCLUSIONS: Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis are the main pathogenic bacteria of respiratory infection in children, and mixed infection is the most common type of infection. The detection rate of pathogenic bacteria varies across seasons and ages. Different pathogenic bacteria have different features of drug resistance, and antibiotics should be selected based on drug sensitivity results.


Assuntos
Infecções Respiratórias , Antibacterianos , Criança , Resistência a Medicamentos , Haemophilus influenzae , Humanos , Lactente , Recém-Nascido , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 595-600, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699188

RESUMO

Objective To explore the role of multidrug resistance gene-1(MDR1)gene in methotrexate(MTX)resistance in patients with rheumatoid arthritis(RA).Methods Fibroblast-like synoviocytes(FLS)from RA patients were infected with recombinant adenovirus Ad-EGFP-MDR1 in vitro to obtain MDR1 over-expressed RA FLS.The transcription level of MDR1 gene and the expression level of its coding product P-glycoprotein(P-gp) rotein were detected by real-time PCR and Western blot analysis.The efflux function was verified by rhodamine 123 efflux assay.The resistance to MTX was detected by MTT assay.Results RA FLS were infected with recombinant adenovirus Ad-EGFP-MDR1;72 hours later,the particles size in MDR1 over-expressed RA FLS increased,the cell volume became larger,and the growth rate decreased.The transcription level of MDR1(1.4325±0.3924 vs.0.0650±0.0070;t=6.035,P=0.004),the expression level of P-gp protein(1.8667±0.2857 vs. 0.9367±0.0551;t=5.536,P=0.005),and the ability of extracellular rhodamine 123(979.43±196.81 vs.1680.06±147.04;t=-4.940,P=0.008) in MDR1 over-expressed RA FLS were significantly higher than those of negative virus control RA-FLS,and the survival rate of MDR1 over-expressed RA FLS was significantly increased at each concentration of MTX(P<0.05).Conclusion The high expression of MDR1 can affect the efflux ability to MTX by up-regulating the expression of P-gp,thus enhancing the drug resistance to MTX in RA FLS.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Resistência a Medicamentos , Fibroblastos/efeitos dos fármacos , Metotrexato/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Artrite Reumatoide/genética , Células Cultivadas , Humanos , Membrana Sinovial/citologia
4.
Medicine (Baltimore) ; 98(41): e17551, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593137

RESUMO

RATIONALE: Refractory edema is characterized by persistent swelling which does not react to diuretic use and sodium restriction. Traditional herbal medicine, Gwack Rhyung Tang and Chunggan extract effectively treated refractory lower limb edema caused by cirrhosis and improved liver function. PATIENT CONCERNS: A 64-year-old male patient with a history of hypertension, diabetes mellitus, hepatic encephalopathy, and cellulitis presented lower limb edema which did not react to diuretics for more than 7 months. DIAGNOSES: Refractory edema caused by cirrhosis. INTERVENTIONS: The patient was treated for 25 days using Gwack Rhyung Tang and Chunggan extract. OUTCOMES: Loss of body weight, decrease in circumferences of both lower limb and improvement of liver function biochemistry results are checked. There was no recurrence or aggravation of the condition up to 3 weeks of follow-up periods. LESSONS: Traditional herbal medicine can be an effective alternative for refractory edema due to cirrhosis with improving liver function.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Edema/tratamento farmacológico , Medicina Tradicional/métodos , Diuréticos/uso terapêutico , Resistência a Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Fibrose/complicações , Medicina Herbária , Humanos , Extremidade Inferior/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
5.
J Drugs Dermatol ; 18(10): 1047, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603633

RESUMO

To the Editor: Acrodermatitis continua of Hallopeau (ACH) is a relatively rare chronic disorder with clinical findings of pustules and erythematous plaques on the digits.1 Although it is a variant of pustular psoriasis, it can be resistant to multiple lines of therapy. We describe for the first time a patient with recalcitrant ACH successfully treated with brodalumab, an interleukin-17 receptor A (IL-17RA) blocking antibody.


Assuntos
Acrodermatite/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Acrodermatite/imunologia , Anticorpos Monoclonais Humanizados , Esquema de Medicação , Resistência a Medicamentos , Dedos , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-17/antagonistas & inibidores , Receptores de Interleucina-17/imunologia , Resultado do Tratamento
6.
Adv Exp Med Biol ; 1164: 119-139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576545

RESUMO

Alternative splicing, the process of removing introns and joining exons of pre-mRNA, is critical for growth, development, tissue homeostasis, and species diversity. Dysregulation of alternative splicing can initiate and drive disease. Aberrant alternative splicing has been shown to promote the "hallmarks of cancer" in both hematological and solid cancers. Of interest, recent work has focused on the role of alternative splicing in prostate cancer and prostate cancer health disparities. We will provide a review of prostate cancer health disparities involving the African American population, alternative RNA splicing, and alternative splicing in prostate cancer. Lastly, we will summarize our work on differential alternative splicing in prostate cancer disparities and its implications for disparate health outcomes and therapeutic targets.


Assuntos
Processamento Alternativo , Resistência a Medicamentos , Disparidades nos Níveis de Saúde , Neoplasias da Próstata , Afro-Americanos/estatística & dados numéricos , Processamento Alternativo/genética , Resistência a Medicamentos/genética , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/fisiopatologia
7.
N Engl J Med ; 381(16): 1513-1523, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31618539

RESUMO

BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS: Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).


Assuntos
Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/cirurgia , Azia/tratamento farmacológico , Omeprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Baclofeno/uso terapêutico , Desipramina/uso terapêutico , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Fundoplicatura , Refluxo Gastroesofágico/complicações , Azia/etiologia , Azia/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Relaxantes Musculares Centrais/uso terapêutico , Qualidade de Vida , Inquéritos e Questionários , Veteranos
8.
J Drugs Dermatol ; 18(9): 943-945, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524993

RESUMO

Raynaud's phenomenon is an exaggerated physiological response of blood vessels in the distal extremities to emotional stress and cold. It can be idiopathic or secondary to a connective tissue disorder, such as scleroderma or systemic lupus erythematosus. Treatment for Raynaud's phenomenon consists primarily of lifestyle modifications; if unsuccessful, pharmacotherapy with dihydropyridine calcium channel blockers can be added. Botulinum toxin (BTX-A) is a neurotoxic protein produced by Clostridium botulinum spores. While most widely known for its cosmetic use, BTX-A has many therapeutic utilities due to its ability to inhibit multiple neurotransmitters. In this report, we present a patient with Raynaud's phenomenon refractory to standard therapies whose symptoms resolved after treatment with BTX-A. Follow-up with the patient after one and five years showed no relapse or recurrence of symptoms. J Drugs Dermatol. 2019;18(9):943-945.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Neurotoxinas/administração & dosagem , Doença de Raynaud/tratamento farmacológico , Pele/patologia , Resistência a Medicamentos , Feminino , Dedos , Humanos , Injeções Subcutâneas , Necrose/tratamento farmacológico , Necrose/etiologia , Doença de Raynaud/complicações , Pele/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
Int Heart J ; 60(5): 1161-1167, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484866

RESUMO

Therapy-resistant ventricular arrhythmias can occur during accidental advanced hypothermic conditions. On the other hand, hypothermic therapy using mild cooling has been successfully accomplished with infrequent ventricular arrhythmia events.To further clarify the therapeutic-resistant arrhythmogenic substrate which develops in hypothermic conditions, an experimental study was performed using a perfusion wedge preparation model of porcine ventricle, and electrophysiological characteristics, inducibility of ventricular arrhythmias, and effects of therapeutic interventions were assessed at 3 target temperatures (37, 32 and 28°C).As the myocardial temperature decreased, myocardial contractions and the number of spontaneous beats deceased. Depolarization (QRS width, stimulus-QRS interval) and repolarization (QT interval, ERP) parameters progressively increased, and dispersion of the ventricular repolarization increased. At 28°C, VF tended to be inducible more frequently (1/11 at 37°C, 1/11 at 32°C, and 5/11 hearts at 28°C), and some VFs at 28°C required greater defibrillation energy to resume basic rhythm.An advanced but not a mild hypothermic condition had an enhanced arrhythmogenic potential in our model. In the advanced hypothermic condition, VF with relatively prolonged F-F intervals and a greater defibrillation energy were occasionally inducible based on the arrhythmogenic substrate characterized as slowed conduction and prolonged repolarization of the ventricle.


Assuntos
Antiarrítmicos/administração & dosagem , Eletrocardiografia/métodos , Hipotermia Induzida/métodos , Fibrilação Ventricular/diagnóstico por imagem , Fibrilação Ventricular/terapia , Análise de Variância , Animais , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , Eletrofisiologia Cardíaca/métodos , Modelos Animais de Doenças , Resistência a Medicamentos , Distribuição Aleatória , Medição de Risco , Suínos , Resultado do Tratamento
10.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(3): 346-348, 2019 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-31544425

RESUMO

Malaria is a parasitic disease which threatens human life and health seriously. Sulfadoxine-pyrimethamine (SP) has been recommended for intermittent preventive treatment of malaria in children and pregnant women, and also used as a compound component of artemisinin based therapy. The mechanisms of SP resistance in P. falciparum involve point mutations in the genes encoding dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), and the drug pressure can also lead to the mutations in the two genes of P. vivax. To provide the information for the formulation of anti-malarial strategies, this article reviews the discovery, application, effect of SP, and the resistance mechanism and research progress of the related genes in P. vivax.


Assuntos
Antimaláricos , Resistência a Medicamentos , Plasmodium vivax , Antimaláricos/farmacologia , Di-Hidropteroato Sintase/genética , Combinação de Medicamentos , Resistência a Medicamentos/genética , Humanos , Malária Falciparum/genética , Mutação , Plasmodium vivax/efeitos dos fármacos , Plasmodium vivax/genética , Pirimetamina/farmacologia , Pesquisa/tendências , Sulfadoxina/farmacologia , Tetra-Hidrofolato Desidrogenase/genética
11.
Parasitol Res ; 118(10): 2989-2999, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473858

RESUMO

Chicken coccidiosis is caused by the apicomplexan parasite Eimeria spp. At present, drug resistance of Eimeria is common because of the indiscriminate use of anticoccidial drugs. The gene encoding surface antigen 10 of Eimeria tenella (EtSAG10) is differentially expressed between drug-resistant and drug-sensitive strains. RNA-seq analysis indicated that this gene was downregulated in strains resistant to maduramicin and diclazuril compared to susceptible strains. EtSAG10 DNA sequence alignment revealed that they contained one and ten mutations in MRR and DZR, compared with DS, respectively. A full-length EtSAG10 cDNA was successfully cloned and expressed, and the polyclonal antibody was prepared. The transcription and translation levels of EtSAG10 were analyzed by quantitative real-time PCR (qPCR) and Western blotting. The localization of EtSAG10 in Spz, Mrz, and parasites in the first asexual stage was determined by indirect immunofluorescence. The potential association of EtSAG10 with sporozoite invasion of host cells was assessed by invasion inhibition assays. The results showed that EtSAG10 had a predicted transmembrane domain at the C-terminal end and a predicted signal peptide at the N-terminal end. EtSAG10 was downregulated in drug-resistant strains, which is consistent with the RNA-seq results. The EtSAG10 protein was localized to the parasite surface and parasitophorous vacuole membrane. This protein was shown to play a role in the infection of chicken intestine by sporozoites.


Assuntos
Antígenos de Protozoários/genética , Antígenos de Superfície/genética , Galinhas/parasitologia , Coccidiose/veterinária , Eimeria tenella/imunologia , Doenças das Aves Domésticas/parasitologia , Animais , Antígenos de Protozoários/metabolismo , Antígenos de Superfície/metabolismo , Coccidiose/parasitologia , Coccidiostáticos/farmacologia , Resistência a Medicamentos/genética , Eimeria tenella/efeitos dos fármacos , Eimeria tenella/genética , Eimeria tenella/crescimento & desenvolvimento , Regulação da Expressão Gênica , Mutação , Esporozoítos/genética , Esporozoítos/imunologia
12.
Med. infant ; 26(3): 267-271, sept. 2019. Tab
Artigo em Espanhol | LILACS | ID: biblio-1023724

RESUMO

Introducción: El estado epiléptico (EE) es la emergencia neurológica más frecuente en pediatría. Los pacientes que no responden al tratamiento estándar con dosis adecuadas de benzodiacepinas seguido de una droga antiepiléptica aceptable son definidos como Estado epiléptico Refractario (ER). Objetivo: caracterizar la población de niños con EE que ingresan a UCIP y determinar qué factores son predictores de refractariedad en esta población. Métodos: Estudio de casos y controles, retrospectivo. Población: niños con EE internados en UCIP desde Febrero 2015 a Febrero 2017. Casos: Estado epiléptico Refractario (ER). Controles: Estado epiléptico No Refractario (ENR). Se calculó el Odds Ratio (OR) individual para las distintas variables en Med Calc. Resultados: Se internaron 35 pacientes de los cuales 12 fueron casos y 23 controles. Hubo fiebre en 77% de los pacientes. En el total de niños estudiados hubo 11% con antecedente de convulsión febril, 11% con antecedente de epilepsia y 9% con antecedente de malformación del SNC. Los niños con antecedente de convulsión febril tuvieron 2,5 veces mayor riesgo de ER (OR: 2,58; IC 95%: 1,17-5,68). Los niños con EE que tenían antecedentes de enfermedad neurológica previa presentaron riesgo de ER 2,6 veces mayor que el grupo control (OR 2,60; IC 95%: 1,24-5,42). Discusión: Dado el aumento en la mortalidad de los pacientes con ER sería importante disponer de más herramientas para predecir este desenlace e iniciar tratamiento oportuno. Resultaría útil entrenar a los padres de niños con antecedente de convulsión febril en la aplicación de medicación antiepiléptica prehospitalaria, esto podría prevenir la farmacorresistencia, el daño neurológico y las complicaciones que acarrea el ingreso a UCIP. (AU)


Introduction: Status epilepticus (SE) is the most common neurologic emergency in children. Patients that do not respond to standard treatment with adequate doses of benzodiazepines followed by an acceptable antiepileptic drug are defined as having refractory status epilepticus (RSE). Objective: To characterize the population of children with SE admitted to the PICU and to determine predictive factors for refractoriness in this population. Methods: A retrospective case-control study was conducted. Population: Children with SE admitted to the PICU between February 2015 and February 2017. Cases: Refractory status pilepticus (RSE). Controls: Non-refractory status epilepticus (NRSE). Individual Odds Ratio (OR) was calculated for different variables using Med Calc. Results: 35 patients were admitted of whom 12 were cases and 23 controls. Overall, 77% of the patients had fever. Of all the children, 11% had a history of febrile seizures, 11% had history of epilepsy and 9% had a CNS malformation. Children with a history of febrile seizures had a 2.5-fold higher risk of developing RSE (OR: 2.58; 95% CI: 1.17-5.68). Children with SE that had a history of neurologic disease had a 2.6-fold higher risk of developing RSE than controls (OR 2.60; 95% CI: 1.24-5.42). Discussion: Given the increased mortality in children with RSE, availability of tools to predict this outcome in order to initiate early treatment is important. It would be useful to train the parents of children with a history of febrile seizures in the prehospital administration of antiepileptic drugs as this may prevent pharmaco-resistance, neurologic damage, and complication related to PICU admission (AU)


Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Estado Epiléptico/complicações , Estado Epiléptico/etiologia , Estado Epiléptico/tratamento farmacológico , Resistência a Medicamentos , Unidades de Terapia Intensiva Pediátrica , Convulsões Febris/tratamento farmacológico , Epilepsia Resistente a Medicamentos/terapia , Anticonvulsivantes/uso terapêutico , Estudos de Casos e Controles , Estudos Retrospectivos
13.
Washington, D.C.; OPAS; 2019-09-20. (OPAS/CDE/19-012).
em Português | PAHO-IRIS | ID: phr-51561

RESUMO

Seguindo a recomendação da OMS, de setembro de 2015, de que a “profilaxia pré-exposição (PrEP) oral deve ser oferecida como uma escolha adicional de prevenção para pessoas com risco substancial de contrair o HIV como parte das abordagens de prevenção combinada do HIV”, parceiros de diversos países indicaram a necessidade de terem orientações práticas sobre como considerar introduzir a PrEP e iniciar a implementação da profilaxia. Atendendo a este pedido, a OMS organizou esta série de módulos informativos para auxiliar a implementação da PrEP para diferentes segmentos populacionais em contextos diversos… Módulo 5: Monitoramento e avaliação. Este módulo destina-se às pessoas responsáveis pelo monitoramento dos programas de PrEP no âmbito nacional e local. Contém informações sobre o método de monitoramento da segurança e efetividade da PrEP, sugerindo indicadores básicos e complementares para notificação local, nacional e global.


Assuntos
HIV , Infecções por HIV , Resistência a Medicamentos , Vigilância em Saúde Pública , Gravidez , Anormalidades Congênitas , Profilaxia Pré-Exposição
15.
Vet Parasitol ; 273: 24-31, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31442889

RESUMO

Haemonchus contortus, one of the most pathogenic of all small ruminant parasites, have developed resistance to all used anthelmintics. Detoxification enzymes, e.g. cytochromes P450 (CYPs) and efflux transporters P-glycoproteins (P-gps), which represent the main defense system against harmful xenobiotics, have been suggested to contribute to drug resistance development. The present study was designed to compare the constitutive expression of individual CYPs and P-gps in females and males of H. contortus adults and to follow up on the changes in expression of these genes in nematodes exposed to sub-lethal concentrations of ivermectin (IVM), which might occur during inaccurate treatment. The adults of inbred susceptible-Edinburgh strain (ISE, MHco3) of H. contortus were used for this purpose. The nematodes were incubated ex vivo with or without IVM (1, 10 and 100 nM) in culture medium for 4, 12 and 24 h. After incubation, total RNA was isolated and expression levels of individual CYPs and P-gps were analyzed using qPCR. Our results showed a great variability in the constitutive expression of individual CYPs and P-gps in H. contortus adults. The constitutive expression as well as the inducibility of CYPs and P-gps significantly differed in males and females. Contact of adult nematodes with sub-lethal IVM concentrations led to only minor changes in expression of CYPs, while expression of several P-gps, particularly pgp-9.2 in males and pgp-10, pgp-11 in females was increased significantly in IVM-exposed nematodes. In conclusion, inaccurate treatment of sheep with IVM might contribute to drug resistance development via increased expression of efflux transporters in H. contortus adults.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Sistema Enzimático do Citocromo P-450/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Haemonchus/efeitos dos fármacos , Ivermectina/farmacologia , Animais , Resistência a Medicamentos/genética , Feminino , Haemonchus/genética , Masculino
16.
Vet Parasitol ; 273: 52-59, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31442894

RESUMO

Gastrointestinal parasites, Parascaris sp. and strongyles, are common in young horses worldwide and control of these parasites is challenged by increasing anthelmintic resistance. Our aim was to identify risk factors for these infections as well as to assess the efficacy of fenbendazole (dose 7.5 mg/kg) and pyrantel embonate (dose 19 mg/kg) against Parascaris sp. We also evaluated association between owner observed symptoms and patent infections with these parasites. Fecal samples were collected from 367 young horses in Finland and a questionnaire study was conducted. Fecal egg counts were performed by Mini-FLOTAC® method. Univariable logistic regression models using patent infection status (Yes/No), separately for Parascaris sp. and strongyle infections as an outcome were run initially to screen potential risk factors collected by the questionnaire. After the initial screening, multiple logistic regression models were constructed and run to account for correlated data structure, risk factors and potential confounders simultaneously. Two significant risk factors for a patent Parascaris sp. infection were found: breeding farm size (p = 0.028) and frequency of horse movements (p = 0.010). Horses originating from large breeding farms were more likely (OR = 2.47, 95% confidence interval (CI) 1.10-5.51) to shed Parascaris sp. eggs upon relocation to training stables compared to horses originating from small breeding farms. Horses living in farms with frequent horse movements to other premises had higher odds (OR = 3.56, 95% CI: 1.35-9.39) of a patent Parascaris sp. infection compared to farms with less frequent horse movements. Risk factors for patent strongyle infection included age (p < 0.001) and season (p = 0.017). Horses were less likely (OR = 0.27, 95% CI: 0.10 - 0.66) to shed strongylid eggs during the spring compared to the winter. Horses excreting over 200 ascarid eggs per gram were included in the anthelmintic efficacy trial. A mean FECR less than 90% was interpreted as presence of anthelmintic resistance. The mean FECR was 98.5% (95% CI: 95.8-100) and 68.0% (95% CI: 52.7-83.3) in the fenbendazole (n = 31) and pyrantel (n = 26) treatment groups, respectively. In conclusion, we identified two new risk factors for patent Parascaris sp. infection; breeding farm size and frequency of horse movements. Reduced efficacy of pyrantel against Parascaris sp. was observed for the second time in Europe. A relatively high Parascaris sp. prevalence in yearlings (34%) and two-year-olds (20%) was observed, which has not been reported earlier. An association between symptoms and a patent Parascaris sp. infection was observed in foals.


Assuntos
Infecções por Ascaridida/veterinária , Ascaridoidea/efeitos dos fármacos , Doenças dos Cavalos/tratamento farmacológico , Pamoato de Pirantel/farmacologia , Pamoato de Pirantel/uso terapêutico , Animais , Infecções por Ascaridida/tratamento farmacológico , Infecções por Ascaridida/epidemiologia , Resistência a Medicamentos , Fenbendazol/farmacologia , Fenbendazol/uso terapêutico , Doenças dos Cavalos/epidemiologia , Cavalos , Fatores de Risco
17.
Mem Inst Oswaldo Cruz ; 114: e190111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31433006

RESUMO

BACKGROUND: In addition to the limited therapeutic arsenal and the side effects of antileishmanial agents, drug resistance hinders disease control. In Brazil, Leishmania braziliensis causes atypical (AT) tegumentary leishmaniasis lesions, frequently refractory to treatment. OBJECTIVES: The main goal of this study was to characterise antimony (Sb)-resistant (SbR) L. braziliensis strains obtained from patients living in Xakriabá indigenous community, Minas Gerais, Brazil. METHODS: The aquaglyceroporin 1-encoding gene (AQP1) from L. braziliensis clinical isolates was sequenced, and its function was evaluated by hypo-osmotic shock. mRNA levels of genes associated with Sb resistance were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Atomic absorption was used to measure Sb uptake. FINDINGS: Although clinical isolates presented delayed recovery time in hypo-osmotic shock, AQP1 function was maintained. Isolate 340 accumulated less Sb than all other isolates, supporting the 65-fold downregulation of AQP1 mRNA levels. Both 330 and 340 isolates upregulated antimony resistance marker (ARM) 56/ARM58 and multidrug resistant protein A (MRPA); however, only ARM58 upregulation was an exclusive feature of SbR field isolates. CA7AE seemed to increase drug uptake in L. braziliensis and represented a tool to study the role of glycoconjugates in Sb transport. MAIN CONCLUSIONS: There is a clear correlation between ARM56/58 upregulation and Sb resistance in AT-harbouring patients, suggesting the use of these markers as potential indicators to help the treatment choice and outcome, preventing therapeutic failure.


Assuntos
Antimônio/farmacologia , Resistência a Medicamentos/genética , Leishmania braziliensis/efeitos dos fármacos , Leishmaniose Cutânea/parasitologia , Proteínas de Protozoários/genética , Tripanossomicidas/farmacologia , Aquagliceroporinas/metabolismo , Resistência a Medicamentos/efeitos dos fármacos , Humanos , Leishmania braziliensis/genética , Testes de Sensibilidade Parasitária , Proteínas de Protozoários/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
18.
Infect Dis Poverty ; 8(1): 69, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31383040

RESUMO

BACKGROUND: The development and spread of artemisinin-resistant Plasmodium falciparum malaria in Greater Mekong Subregion has created impetus for continuing global monitoring of efficacy of artemisinin-based combination therapies (ACTs). This post analyses is aimed to evaluate changes in early treatment response markers 10 years after the adoption of ACTs as first-line treatments of uncomplicated falciparum malaria in Nigeria. METHODS: At 14 sentinel sites in six geographical areas of Nigeria, we evaluated treatment responses in 1341 children under 5 years and in additional 360 children under 16 years with uncomplicated malaria enrolled in randomized trials of artemether-lumefantrine versus artesunate-amodiaquine at 5-year interval in 2009-2010 and 2014-2015 and at 2-year interval in 2009-2010 and 2012-2015, respectively after deployment in 2005. RESULTS: Asexual parasite positivity 1 day after treatment initiation (APPD1) rose from 54 to 62% and 2 days after treatment initiation from 5 to 26% in 2009-2010 to 2014-2015 (P = 0.002 and P <  0.0001, respectively). Parasite clearance time increased significantly from 1.6 days (95% confidence interval [CI]: 1.55-1.64) to 1.9 days (95% CI, 1.9-2.0) and geometric mean parasite reduction ratio 2 days after treatment initiation decreased significantly from 11 000 to 4700 within the same time period (P <  0.0001 for each). Enrolment parasitaemia > 75 000 µl- 1, haematocrit > 27% 1 day post-treatment initiation, treatment with artemether-lumefantrine and enrolment in 2014-2015 independently predicted APPD1. In parallel, Kaplan-Meier estimated risk of recurrent infections by day 28 rose from 8 to 14% (P = 0.005) and from 9 to 15% (P = 0.02) with artemether-lumefantrine and artesunate-amodiaquine, respectively. Mean asexual parasitaemia half-life increased significantly from 1.1 h to 1.3 h within 2 years (P <  0.0001). CONCLUSIONS: These data indicate declining parasitological responses through time to the two ACTs may be due to emergence of parasites with reduced susceptibility or decrease in immunity to the infections in these children. TRIAL REGISTRATION: Pan African Clinical Trial Registration PACTR201508001188143 , 3 July 2015; PACTR201508001191898 , 7 July 2015 and PACTR201508001193368 , 8 July 2015 PACTR201510001189370 , 3 July 2015; PACTR201709002064150 , 1 March 2017; https://www.pactr.samrca.ac.za.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Resistência a Medicamentos , Malária Falciparum/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Adolescente , Amodiaquina/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Lactente , Masculino , Nigéria
19.
Malar J ; 18(1): 281, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438950

RESUMO

The Global Technical Strategy 2016-2030 of the World Health Organization (WHO) has the ambitious goal of malaria being eliminated from at least 35 countries by 2030. However, in areas with once-stable malaria transmission, the reservoir of human infection may be intermittently symptomatic or fully silent yet still lead to transmission, posing a serious challenge to elimination. Mass drug administration (MDA), defined as the provision of a therapeutic dose of an effective anti-malarial drug to the entire target population, irrespective of infection status or symptoms, is one strategy to combat the silent human reservoir of infection. MDA is currently recommended by the WHO as a potential strategy for the elimination of Plasmodium falciparum malaria in areas approaching interruption of transmission, given the prerequisites of good access to case management, effective vector control and surveillance, and limited potential for reintroduction. Recent community randomized controlled trials of MDA with dihydroartemisinin-piperaquine, implemented as part of a comprehensive package of interventions, have shown this strategy to be safe and effective in significantly lowering the malaria burden in pre-elimination settings. Here it is argued that effectively implemented MDA should be kept in the elimination toolbox as a potential strategy for P. falciparum elimination in a variety of settings, including islands, appropriate low transmission settings, and in epidemics and complex emergencies. Effectively implemented MDA using an ACT has been shown to be safe, unrelated to the emergence of drug resistance, and may play an important role in sufficiently lowering the malaria burden to allow malaria transmission foci to be more easily identified, and to allow elimination programmes to more feasibly implement case-based surveillance and follow-up activities. To be most impactful and guard against drug resistance, MDA should use an ACT, achieve high programmatic coverage and adherence, be implemented when transmission is lowest in areas of limited risk of immediate parasite reintroduction, and must always be implemented only once good access to case management, high coverage of effective vector control, and strong surveillance have been achieved. If these considerations are taken into account, MDA should prove to be a valuable tool for the malaria elimination toolbox.


Assuntos
Antimaláricos/uso terapêutico , Erradicação de Doenças/métodos , Malária/prevenção & controle , Administração Massiva de Medicamentos/métodos , Erradicação de Doenças/estatística & dados numéricos , Combinação de Medicamentos , Resistência a Medicamentos , Humanos , Administração Massiva de Medicamentos/ética , Administração Massiva de Medicamentos/estatística & dados numéricos
20.
Malar J ; 18(1): 280, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438951

RESUMO

BACKGROUND: The ability of Plasmodium falciparum parasites to develop resistance to widely used anti-malarials threatens malaria control and elimination efforts. Regular drug efficacy monitoring is essential for ensuring effective treatment policies. In low transmission settings where therapeutic efficacy studies are often not feasible, routine surveillance for molecular markers associated with anti-malarial resistance provides an alternative for the early detection of emerging resistance. Such a longitudinal survey of changes in the prevalence of selected molecular markers of resistance was conducted in the malaria-endemic regions of Mpumalanga Province, South Africa, where malaria elimination at a district-level is being pursued. METHODS: Molecular analyses to determine the prevalence of alleles associated with resistance to lumefantrine (mdr86N, crt76K and mdr1 copy number variation) and sulfadoxine-pyrimethamine (dhfr triple, dhps double, SP quintuple) were conducted between 2001 and 2018, while artemisinin resistance markers (kelch13 mutations) were assessed only in 2018. RESULTS: Parasite DNA was successfully amplified from 1667/2393 (70%) of malaria-positive rapid diagnostic tests routinely collected at primary health care facilities. No artemisinin resistance-associated kelch13 mutations nor amplification of the mdr1 gene copy number associated with lumefantrine resistance were observed. However, prevalence of both the mdr86N and crt76K alleles increased markedly over the study period, with all isolates collected in 2018 carrying these markers. SP quintuple mutation prevalence increased steadily from 14% in 2001 to 96% in 2018. Mixed alleles at any of the codons assessed were rare by 2018. CONCLUSION: No kelch13 mutations confirmed or suspected to be associated with artemisinin resistance were identified in 2018. Although parasites carrying the mdr86N and crt76K alleles associated with reduced lumefantrine susceptibility were strongly selected for over the study period, nearing fixation by 2018, the marker for lumefantrine resistance, namely increased mdr1 copy number, was not observed in this study. The increase in mdr86N and crt76K allele prevalence together with intense regional artemether-lumefantrine drug pressure, raises concern regarding the sustained artemether-lumefantrine efficacy. Regular, rigorous anti-malarial resistance marker surveillance across all three South African malaria-endemic provinces to inform case management is recommended.


Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Resistência a Medicamentos/genética , Lumefantrina/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/genética , Pirimetamina/farmacologia , Sulfadoxina/farmacologia , Testes Diagnósticos de Rotina , Combinação de Medicamentos , Quimioterapia Combinada , Marcadores Genéticos , Plasmodium falciparum/genética , Proteínas de Protozoários/metabolismo , Seleção Genética , África do Sul
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