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1.
Thorax ; 77(12): 1220-1228, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35027473

RESUMO

BACKGROUND: Culture-based microbiological investigation of hospital-acquired or ventilator-associated pneumonia (HAP or VAP) is insensitive, with aetiological agents often unidentified. This can lead to excess antimicrobial treatment of patients with susceptible pathogens, while those with resistant bacteria are treated inadequately for prolonged periods. Using PCR to seek pathogens and their resistance genes directly from clinical samples may improve therapy and stewardship. METHODS: Surplus routine lower respiratory tract samples were collected from intensive care unit patients about to receive new or changed antibiotics for hospital-onset lower respiratory tract infections at 15 UK hospitals. Testing was performed using the BioFire FilmArray Pneumonia Panel (bioMérieux) and Unyvero Pneumonia Panel (Curetis). Concordance analysis compared machine and routine microbiology results, while Bayesian latent class (BLC) analysis estimated the sensitivity and specificity of each test, incorporating information from both PCR panels and routine microbiology. FINDINGS: In 652 eligible samples; PCR identified pathogens in considerably more samples compared with routine microbiology: 60.4% and 74.2% for Unyvero and FilmArray respectively vs 44.2% by routine microbiology. PCR tests also detected more pathogens per sample than routine microbiology. For common HAP/VAP pathogens, FilmArray had sensitivity of 91.7%-100.0% and specificity of 87.5%-99.5%; Unyvero had sensitivity of 50.0%-100.0%%, and specificity of 89.4%-99.0%. BLC analysis indicated that, compared with PCR, routine microbiology had low sensitivity, ranging from 27.0% to 69.4%. INTERPRETATION: Conventional and BLC analysis demonstrated that both platforms performed similarly and were considerably more sensitive than routine microbiology, detecting potential pathogens in patient samples reported as culture negative. The increased sensitivity of detection realised by PCR offers potential for improved antimicrobial prescribing.


Assuntos
Infecção Hospitalar , Pneumonia Associada à Ventilação Mecânica , Pneumonia , Humanos , Reação em Cadeia da Polimerase Multiplex/métodos , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/microbiologia , Teorema de Bayes , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Unidades de Terapia Intensiva , Antibacterianos/uso terapêutico , Reino Unido , Pneumonia/diagnóstico
2.
Hum Exp Toxicol ; 39(5): 577-595, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31884827

RESUMO

Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies.


Assuntos
Benzeno/toxicidade , Carcinógenos/toxicidade , Células-Tronco Hematopoéticas/efeitos dos fármacos , Neoplasias/induzido quimicamente , Animais , Benzeno/farmacocinética , Carcinógenos/farmacocinética , Epigênese Genética , Hematopoese/efeitos dos fármacos , Humanos , Neoplasias/genética , Nicho de Células-Tronco/efeitos dos fármacos
3.
Lancet Respir Med ; 5(6): 492-499, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28483402

RESUMO

BACKGROUND: Antibiotics do not reduce mortality or short-term treatment non-response in patients receiving treatment for acute exacerbations of COPD in an outpatient setting. However, the long-term effects of antibiotics are unknown. The aim of this study was to investigate if the antibiotic doxycycline added to the oral corticosteroid prednisolone prolongs time to next exacerbation in patients with COPD receiving treatment for an exacerbation in the outpatient setting. METHODS: In this randomised double-blind placebo-controlled trial, we recruited a cohort of patients with COPD from outpatient clinics of nine teaching hospitals and three primary care centres in the Netherlands. Inclusion criteria were an age of at least 45 years, a smoking history of at least 10 pack-years, mild-to-severe COPD (Global Initiative of Chronic Obstructive Lung Disease [GOLD] stage 1-3), and at least one exacerbation during the past 3 years. Exclusion criteria were poor mastery of the Dutch language, poor cognitive functioning, known allergy to doxycycline, pregnancy, and a life expectancy of shorter than 1 month. If a participant had an exacerbation, we randomly assigned them (1:1; with permuted blocks of variable sizes [ranging from two to ten]; stratified by GOLD stage 1-2 vs 3) to a 7 day course of oral doxycycline 100 mg daily (200 mg on the first day) or placebo. Exclusion criteria for randomisation were fever, admission to hospital, and current use of antibiotics or use within the previous 3 weeks. Patients in both groups received a 10 day course of 30 mg oral prednisolone daily. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary outcome was time to next exacerbation in all randomly allocated patients except for those incorrectly randomly allocated who did not meet the inclusion criteria or met the exclusion criteria. This trial is registered with the Netherlands Trial Register, number NTR2499. FINDINGS: Between Dec 22, 2010, and Aug 6, 2013, we randomly allocated 305 (34%) patients from the cohort of 887 patients to doxycycline (152 [50%]) or placebo (153 [50%]), excluding four (1%) patients (two [1%] from each group) who were incorrectly randomly allocated from the analysis. 257 (85%) of 301 patients had a next exacerbation (131 [87%] of 150 in the doxycycline group vs 126 [83%] of 151 in the placebo group). Median time to next exacerbation was 148 days (95% CI 95-200) in the doxycycline group compared with 161 days (118-211) in the placebo group (hazard ratio 1·01 [95% CI 0·79-1·31]; p=0·91). We did not note any significant differences between groups in the frequency of adverse events during the first 2 weeks after randomisation (47 [31%] of 150 in the doxycycline group vs 53 [35%] of 151 in the placebo group; p=0·54) or in serious adverse events during the 2 years of follow-up (42 [28%] vs 43 [29%]; p=1). INTERPRETATION: In patients with mild-to-severe COPD receiving treatment for an exacerbation in an outpatient setting, the antibiotic doxycycline added to the oral corticosteroid prednisolone did not prolong time to next exacerbation compared with prednisolone alone. These findings do not support prescription of antibiotics for COPD exacerbations in an outpatient setting. FUNDING: Netherlands Organization for Health Research and Development.


Assuntos
Antibacterianos/administração & dosagem , Doxiciclina/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração Oral , Corticosteroides/administração & dosagem , Idoso , Antibacterianos/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Doxiciclina/efeitos adversos , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Prednisolona/administração & dosagem , Índice de Gravidade de Doença , Fatores de Tempo
4.
Australas Psychiatry ; 22(4): 366-369, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24820291

RESUMO

OBJECTIVE: The purpose of this study was to investigate restraint use in Australian emergency departments (EDs). METHOD: A retrospective audit of restraint incidents in four EDs (from 1 January 2010 to 31 December 2011). RESULTS: The restraint rate was 0.04% of total ED presentations. Males and females were involved in similar numbers of incidents. Over 90% of restrained patients had a mental illness diagnosis and were compulsorily hospitalised. Mechanical restraint with the use of soft shackles was the main method used. Restraint was enacted to prevent harm to self and/or others. Median incident duration was 2 hours 5 minutes. CONCLUSIONS: In order to better integrate the needs of mental health clients, consideration is needed as to what improvements to procedures and the ED environment can be made. EDs should particularly focus on reducing restraint duration and the use of hard shackles.

5.
Water Sci Technol ; 63(3): 491-501, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21278472

RESUMO

The use of coagulation and flocculation for tertiary treatment of pulp and paper mill effluent was investigated, where the evaluation was based on the removal of nitrogen (N), phosphorus (P) and BOD from post-coagulated wastewater. The study was undertaken on laboratory scale aerobic stabilisation basins (ASB). Two post coagulated (alum) wastewaters were studied, where the BOD:N:P ratios were 100:1.3:0.06 and 100:1.3:0.3. These wastewaters were treated in two identical concurrent simulations (A & B). The influent ratio for 'A' was selected representing the composition of actual coagulated Pinus radiata sulfite pulp effluent mixed with paper mill effluent. The input composition for 'B' represented a typical P concentration found in existing pulp and paper mill effluents. Unmodified sludge collected from a mill-pond was added at 4% v/v to each simulation replicating the treatment conditions at full-scale. Similar high percentage removals of BOD and COD occurred after 28 days (two HRTs) which were 94 and 67% respectively for 'A', and 98 and 70% respectively for 'B', where both remained at steady state during the third HRT. A statistical analysis of the data revealed that there was no significant difference in the sample variance of the BOD and COD results.


Assuntos
Análise da Demanda Biológica de Oxigênio , Resíduos Industriais/análise , Nitrogênio/análise , Fósforo/análise , Pinus/metabolismo , Sulfitos/isolamento & purificação , Eliminação de Resíduos Líquidos/instrumentação , Aerobiose , Biodegradação Ambiental , Reatores Biológicos , Simulação por Computador , Floculação , Papel , Projetos Piloto , Água/normas
6.
Plant J ; 47(6): 851-63, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16889645

RESUMO

The oxidative burst is an early response to pathogen attack leading to the production of reactive oxygen species (ROS) including hydrogen peroxide. Two major mechanisms involving either NADPH oxidases or peroxidases that may exist singly or in combination in different plant species have been proposed for the generation of ROS. We identified an Arabidopsis thaliana azide-sensitive but diphenylene iodonium-insensitive apoplastic oxidative burst that generates H(2)O(2) in response to a Fusarium oxysporum cell-wall preparation. Transgenic Arabidopsis plants expressing an anti-sense cDNA encoding a type III peroxidase, French bean peroxidase type 1 (FBP1) exhibited an impaired oxidative burst and were more susceptible than wild-type plants to both fungal and bacterial pathogens. Transcriptional profiling and RT-PCR analysis showed that the anti-sense (FBP1) transgenic plants had reduced levels of specific peroxidase-encoding mRNAs, including mRNAs corresponding to Arabidopsis genes At3g49120 (AtPCb) and At3g49110 (AtPCa) that encode two class III peroxidases with a high degree of homology to FBP1. These data indicate that peroxidases play a significant role in generating H(2)O(2) during the Arabidopsis defense response and in conferring resistance to a wide range of pathogens.


Assuntos
Arabidopsis/fisiologia , Fungos/patogenicidade , Peroxidases/metabolismo , Explosão Respiratória , Arabidopsis/enzimologia , Arabidopsis/microbiologia , Fumonisinas/metabolismo , Perfilação da Expressão Gênica , Plantas Geneticamente Modificadas , Espécies Reativas de Oxigênio , Reação em Cadeia da Polimerase Via Transcriptase Reversa
7.
J Exp Bot ; 57(8): 1817-27, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16720603

RESUMO

The present understanding of ROS generation in the defence response of Arabidopsis thaliana is reviewed. Evidence suggests that the apoplastic oxidative burst generated during basal resistance is peroxidase-dependent. The ROS generated during this basal resistance may serve to activate NADPH oxidase during the R-gene-mediated hypersensitive response. The processes involved in the production of reactive oxygen species in A. thaliana cell suspension cultures in response to an elicitor from Fusarium oxysporum are investigated in the present work. This system appears analogous to the production of ROS during the basal resistance response in French bean, which is peroxidase-dependent. A panel of modulators effective in other pathogen elicitor and plant cell systems has been used to investigate the Arabidopsis signalling pathways and the plant cell responses involved. Thus as in other systems, an early calcium influx into the cytosolic compartment, a rapid efflux of K(+) and Cl(-), and extracellular alkalinization of elicited cell cultures has been found. However the alkalinization is not sufficient to stimulate the apoplastic oxidative burst by itself, unlike in French bean, although vectorial ion fluxes are needed. A secretory component which is sensitive to monensin and N-ethylmaleimide and insensitive to brefeldin A may also be necessary for the release and provision of substrates for peroxidase-dependent generation of H(2)O(2).


Assuntos
Arabidopsis/metabolismo , Fusarium/fisiologia , Doenças das Plantas , Espécies Reativas de Oxigênio/metabolismo , Arabidopsis/microbiologia , Cálcio/fisiologia , Morte Celular/fisiologia , Células Cultivadas , AMP Cíclico/fisiologia , Exocitose/fisiologia , Concentração de Íons de Hidrogênio , Potássio/fisiologia , Transdução de Sinais
8.
Phytochemistry ; 61(7): 771-80, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12453569

RESUMO

UDP-glucuronic acid decarboxylase catalyses the reaction responsible for the formation of UDP-xylose and commits assimilate for the biosynthesis of cell wall polysaccharides and glycosylation of proteins. Xylose-rich polymers such as xylans are a feature of dicot secondary walls. Thus a cell culture system of tobacco transformed with the ipt gene from Agrobacterium tumefaciens for cytokinin production and which when manipulated with auxin and sucrose leads to induction of xylogenesis, has been used as a source for purification of the enzyme. UDP-glucuronic acid decarboxylase was purified by ion-exchange, gel filtration and affinity chromatography on Reactive Brown-Agarose. The native enzyme had an apparent M(r) of 220,000 which yielded a single subunit of 87,000 when analysed on SDS-PAGE using silver staining. This appears to be a novel form of the enzyme since a gene family encoding polypeptides around M(r) 40,000 with homology to the fungal enzyme also exists in plants. Using an antibody raised to the native 87 kDa form of the enzyme, this decarboxylase was localised mainly to to cambium and differentiating vascular tissue in tobacco stem, consistent with a role in the provision of UDP-xylose for the synthesis of secondary wall xylan. Further analysis using immunogold electron microscopy localised the 87 kDa UDP-glucuronic acid decarboxylase to the cytosol of developing vascular tissue.


Assuntos
Carboxiliases/metabolismo , Nicotiana/enzimologia , Peptídeos/química , Peptídeos/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Anticorpos/química , Carboxiliases/imunologia , Linhagem Celular Transformada , Cromatografia por Troca Iônica , Técnicas de Cultura , Eletroforese em Gel de Poliacrilamida , Coloide de Ouro , Imuno-Histoquímica/métodos , Microscopia Eletrônica de Varredura/métodos , Peso Molecular , Peptídeos/isolamento & purificação , Proteínas de Plantas/isolamento & purificação , Testes de Precipitina , Coloração e Rotulagem , Nicotiana/citologia , Nicotiana/genética
9.
Plant Mol Biol ; 49(5): 533-44, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12090628

RESUMO

Changes in protein kinase activity have been investigated during the early response of suspension cultured cells of French bean to fungal elicitor. One of the kinases activated has a known target, phenylalanine ammonia-lyase (PAL), which has an important role in plant defence responses, and was purified. Kinase acivity during purification was monitored for both the PAL-derived peptide and syntide-2, which it also phosphorylated. The kinase had an Mr of 55,000 on the basis of gel migration, 45Ca2+ binding, autophosphorylation and phosphorylation of various substrates using in-gel assays. The kinase has been characterised with respect to kinetics and other properties in vitro and appears to be a CDPK. In-gel assays were also used to show that this kinase and a number of other CDPKs of similar Mr showed complex changes in elicitor-treated suspension-cultured cells of French bean. An activation was observed within 10 min and was maintained for up to 4 h. The time course of activation was different from MAP kinase and casein kinase assayed in the same extracts. However, at 5 min after addition of elicitor there is a transient inactivation of the CDPKs before activation. This inactivation can be mimicked by adding forskolin to the cells 30 min before elicitation, which brings about changes in the cellular pH. Forskolin potentiates the oxidative burst when elicitor is subsequently added while the CDPK cannot be activated by elicitor upon forskolin treatment. In contrast, intracellular acidification brought about by forskolin brings about slight activation of MAPkinase.


Assuntos
Phaseolus/genética , Fenilalanina Amônia-Liase/metabolismo , Proteínas de Plantas , Proteínas Quinases/genética , Benzilaminas/farmacologia , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Eletroforese em Gel de Poliacrilamida , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Glucose/farmacologia , Isoquinolinas/farmacologia , Peso Molecular , Phaseolus/citologia , Phaseolus/enzimologia , Fosforilação , Inibidores de Proteínas Quinases , Proteínas Quinases/metabolismo , Especificidade por Substrato , Sulfonamidas/farmacologia
10.
J Exp Bot ; 53(372): 1367-76, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11997382

RESUMO

The oxidative burst, the generation of reactive oxygen species (ROS) in response to microbial pathogen attack, is a ubiquitous early part of the resistance mechanisms of plant cells. It has also become apparent from the study of a number of plant-pathogen interactions and those modelled by elicitor treatment of cultured cells that there may be more than one mechanism operating. However, one mechanism may be dominant in any given species. NADPH oxidases have been implicated in a number of systems and have been cloned and characterized. However, the enzyme system which is the major source of ROS in French bean (Phaseolus vulgaris) cells treated with a cell wall elicitor from Colletotrichum lindemuthianum, appears to be dependent on an exocellular peroxidase. The second component, the extracellular alkalinization, occurs as a result of the Ca(2+) and proton influxes and the K(+) efflux common to most elicitation systems as one of the earliest responses. The third component, the actual reductant/substrate, has remained elusive. The low molecular weight compound composition of apoplastic fluid was compared before and after elicitation. The substrate only becomes available some min after elicitation and can be extracted, so that by comparing the profiles by LC-MS it has been possible to identify possible substrates. The mechanism has proved to be complex and may involve a number of low molecular weight components. Stimulation of H(2)O(2) production was observed with saturated fatty acids such as palmitate and stearate without concomitant oxylipin production. This biochemical evidence is supported by immunolocalization studies on papillae forming at bacterial infection sites that show the peroxidase isoform present at sites of H(2)O(2) production revealed by cerium chloride staining together with the cross-linked wall proteins and callose and callose synthase. The peroxidase has been cloned and expressed in Pichia pastoris and has been shown to catalyse the oxidation reaction with the same kinetics as the purified enzyme. Furthermore, Arabidopsis plants transformed heterologously using the French bean peroxidase in antisense orientation have proved to be highly susceptible to bacterial and fungal pathogens. Thus it is possible that Arabidopsis is another species with the potential to mount an apoplastic oxidative burst and these transformed plant lines may be useful to identify the peroxidase that is responsible.


Assuntos
Doenças das Plantas/microbiologia , Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/microbiologia , Colletotrichum/crescimento & desenvolvimento , Ácidos Graxos/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Oxirredução , Peroxidase/química , Peroxidase/genética , Peroxidase/metabolismo , Phaseolus/genética , Phaseolus/metabolismo , Phaseolus/microbiologia , Plantas/genética , Plantas/microbiologia , Conformação Proteica , Transdução de Sinais
11.
New Phytol ; 151(1): 185-194, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33873377

RESUMO

• Modulators of cAMP, calcium and G proteins were used to treat bean (Phaseolus vulgaris) cells before addition of an elicitor from Colletotrichum lindemuthianum in order to elucidate the early steps of signal transduction leading to the production of the apoplastic oxidative burst. • Hydrogen peroxide production by elicited bean cells was monitored with luminol-or xylenol-orange-based assays. • Pretreatment with forskolin, dibutyryl cAMP or the Ca2+ ionophore A23187 enhanced the production of reactive oxygen species (ROS). The Ca2+ channel blocker, verapamil, and the calmodulin antagonist W7 led to a decreased oxidative burst and cancelled the dibutyryl cAMP effect. The production of ROS was increased by cholera toxin (CTX), an activator of G proteins. • Thus, an increase of cytosolic calcium ([Ca2+ ]cyt ) mediated through an increased level of cAMP is required for ROS production. The data support a role for G proteins and cAMP in extracellular alkalinization and Ca2+ influx, possibly in the provision of a reductant, which with the extracellular peroxidase, are required for the apoplastic oxidative burst.

12.
Artigo em Inglês | MEDLINE | ID: mdl-11414416

RESUMO

A study on the reliability of an enzyme linked immunosorbent assay (ELISA) for the detection of typhoid fever, the ELISA-Ty test, was conducted, comprising 44 children suffering from bacteriologically confirmed typhoid fever based on the finding of a positive blood culture for Salmonella typhi, 44 children with fever caused by diseases other than typhoid fever based on the finding of negative culture of blood, urine and stool for S. typhi, and 120 healthy children as controls. This ELISA-Ty test measures the concentration of IgM and of IgG against S. typhi in serum. This test is an indirect ELISA test, based on a method that makes use of a mixture of OMPs (outer membrane proteins) in equal proportion serving as antigen, obtained from different strains of S. typhi which are prevalent locally, peroxidase goat antihuman IgG or IgM (Sigma) as conjugate and orthophenylenediamine (Sigma) as chromogen of the substrate. The result of the test was obtained through the assessment of the end product, using a micro ELISA reader (Behring) at wave length of 490 nm. The data revealed that the mean absorbent values found in children with typhoid fever, for IgM and IgG, were significantly higher (p < 0.05) when compared to those in children with non-typhoid fever as well as to those found in children of the control group. The results of this study confirm that the ELISA-Ty test has a high reliability for the detection of typhoid fever in children, based on the finding of a degree of diagnostic sensitivity as high as 95.45% and 90.91% for respectively IgM and IgG, a diagnostic specificity as high as 93.33% for IgM as well as for IgG, a high diagnostic efficiency (94.32% for IgM and 92.05% for IgG), a high diagnostic positive predictive value of 93.33% for IgM and 93.02% for IgG, high negative predictive values of 95.35% for IgM and 91.11% for IgG for use under clinical as well as under field conditions.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Febre Tifoide/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Lactente , Masculino , Sensibilidade e Especificidade , Febre Tifoide/enzimologia
13.
Trans R Soc Trop Med Hyg ; 90(4): 409-11, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8882190

RESUMO

In February 1995 we surveyed to chloroquine among patients with Plasmodium vivax malaria at Nias Island, in the Indian Ocean near north-western Sumatra, Indonesa. The subjects, 21 indigenous males and females (6-50 years old) infected with > 40 asexual blood stage parasites of P. vivax per microliter of blood, had mild symptoms or none at all. Seven of these patients had > 100 ng/mL whole blood chloroquine levels before the first supervised dose of chloroquine (3 doses of 10 mg/kg, 10 mg/kg, 5 mg/kg of base given at 24 h intervals). Whole blood chloroquine levels on the last day of dosing confirmed normal absorption (range 413-3248, mean 1141, SD 616 ng/mL). Blood films were examined on days 0, 2, 4, 7, 11, 14, 18, 21 and 28 after initiating therapy. Three patients had recurrent asexual P. vivax parasitaemias between days 14 and 18, despite effective levels of chloroquine in whole blood (> or = 100 ng/mL) at the time of recurrence. Resistance to standard chloroquine therapy by P. vivax appeared in 14% of infections among residents of Nias.


Assuntos
Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Resistência a Medicamentos , Malária Vivax/tratamento farmacológico , Adolescente , Adulto , Antimaláricos/sangue , Criança , Cloroquina/análogos & derivados , Cloroquina/sangue , Feminino , Humanos , Indonésia , Malária Falciparum/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva
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