RESUMO
Cefiderocol, a novel siderophore cephalosporin, demonstrates promising in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenemase-producing strains. Nonetheless, only a few reports are available regarding the acquisition of resistance in clinical settings, primarily due to its recent usage. This study aimed to investigate cefiderocol resistance using an in vitro resistance development model to gain insights into the underlying molecular resistance mechanisms. Cefiderocol susceptible reference strains (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) and a clinical Acinetobacter baumannii complex isolate were exposed to increasing cefiderocol concentrations using a high-throughput resistance development model. Cefiderocol susceptibility testing was performed using broth microdilution. Whole-genome sequencing was employed to identify newly acquired resistance mutations. Our in vitro resistance development model led to several clones of strains exhibiting cefiderocol resistance, with MIC values 8-fold to 512-fold higher than initial levels. In total, we found 42 different mutations in 26 genes, of which 35 could be described for the first time. Putative loss-of-function mutations were detected in the envZ, tonB, and cirA genes in 13 out of 17 isolates, leading to a decrease in cefiderocol influx. Other potential resistance mechanisms included multidrug efflux pumps (baeS, czcS, nalC), antibiotic-inactivating enzymes (ampR, dacB), and target mutations in penicillin-binding-protein genes (mrcB). This study reveals new insights into underlying molecular resistance mechanisms against cefiderocol. While mutations leading to reduced influx via iron transporters was the most frequent resistance mechanism, we also detected several other novel resistance mutations causing cefiderocol resistance.
RESUMO
Personal protective equipment and adherence to disinfection protocols are essential to prevent nosocomial severe acute respiratory syndrome coronavirus (SARS-CoV-2) transmission. Here, we evaluated infection control measures in a prospective longitudinal single-center study at the Vienna General Hospital, the biggest tertiary care center in Austria, with a structurally planned low SARS-CoV-2 exposure. SARS-CoV-2-specific antibodies were assessed by Abbott ARCHITECT chemiluminescent assay (CLIA) in 599 health care workers (HCWs) at the start of the SARS-CoV-2 epidemic in early April and two months later. Neutralization assay confirmed CLIA-positive samples. A structured questionnaire was completed at both visits assessing demographic parameters, family situation, travel history, occupational coronavirus disease 2019 (COVID-19) exposure, and personal protective equipment handling. At the first visit, 6 of 599 participants (1%) tested positive for SARS-CoV-2-specific antibodies. The seroprevalence increased to 1.5% (8/553) at the second visit and did not differ depending on the working environment. Unprotected SARS-CoV-2 exposure (p = 0.003), positively tested family members (p = 0.04), and travel history (p = 0.09) were more frequently reported by positively tested HCWs. Odds for COVID-19 related symptoms were highest for congestion or runny nose (p = 0.002) and altered taste or smell (p < 0.001). In conclusion, prevention strategies proved feasible in reducing the risk of transmission of SARS-CoV-2 from patients and among HCWs in a low incidence hospital, not exceeding the one described in the general population.
Assuntos
COVID-19 , Áustria , Pessoal de Saúde , Humanos , Incidência , Controle de Infecções , Estudos Prospectivos , SARS-CoV-2 , Estudos Soroepidemiológicos , Centros de Atenção TerciáriaRESUMO
Respiratory syncytial virus (RSV) testing is generally available in most care centres, but it is rarely performed because clinicians' seldom suspect RSV to be the underlying pathogen in adults with respiratory disease. Here, we evaluate the impact of broad combined influenza/RSV testing on the clinical practice. Overall, 103 patients were tested positively for RSV. Our study indicates that positively tested patients were mostly of advanced age and suffered from chronic diseases. Mortality was significant in our cohort and higher in patients with advanced age. Further, we report a significant increase in detected RSV cases but also in detection rate. Together, these findings suggest that implementation of a combined influenza/RSV testing led to a significant increase in detection rate, supported clinicians establishing the correct diagnosis and allowed a safe and controlled handling of RSV patients.
Assuntos
Infecções por Vírus Respiratório Sincicial/mortalidade , Vírus Sinciciais Respiratórios , Adulto , Idoso , Áustria/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/diagnóstico , Estudos RetrospectivosRESUMO
To update information on the epidemiological situation and national capacity for detection, surveillance and containment of carbapenem-resistant Acinetobacter baumannii (CRAb) in Europe, we performed a survey in 37 countries. Nine countries reported regional or inter-regional spread and seven an endemic situation. Laboratories with a reference function, surveillance systems, and a national containment plan for CRAb existed in 30, 23 and eight countries, respectively. A pan-European molecular survey would provide in-depth understanding of the CRAb epidemiology.
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Infecções por Acinetobacter , Acinetobacter baumannii , Carbapenêmicos , Farmacorresistência Bacteriana , Laboratórios , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/efeitos dos fármacos , Carbapenêmicos/farmacologia , Europa (Continente)/epidemiologia , Humanos , Laboratórios/organização & administraçãoRESUMO
BACKGROUND: Human toxocariasis occurs worldwide and is caused by nematodes of the species of the genus Toxocara. Infection occurs by the ingestion of eggs and is usually asymptomatic or oligosymptomatic. However, severe manifestations occur. The burden of disease and its public health impact remain ill-defined. The aim of this review was to summarize all available data on the seroprevalence of toxocariasis on the African continent and factors associated with seropositivity. METHODS: Twenty-seven original papers published between 1991 and 2017 were identified that provided data suitable for this review. Case-control studies were included and the seroprevalence in the (healthy) control group was used as a surrogate parameter. RESULTS: Antibodies against Toxocara spp. were found to be frequent in most populations and regions in Africa with the exception of two publications, one from the Democratic Republic of the Congo and one from Djibouti, where all participants were seronegative. The highest proportion of participants with antibodies was found on the island of La Réunion with 359 out 387 study participants being positive (92.8%). Factors associated with seropositivity were reported across studies, including-among others-older age, contact with soil via geophagia, agricultural activity or playing with soil, contact with animals, especially dogs, and low socio-economic status, defined as absence of water supply or poor housing. Three Egyptian studies found male gender to be associated with toxocariasis, whereas in La Réunion females were at increased risk. CONCLUSIONS: Exposure to toxocariasis seems to be very frequent and common in large parts of the African continent. However, no data are available for most countries. The public health impact of human toxocariasis and the frequency of severe manifestations remain unclear.
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Toxocara , Toxocaríase/epidemiologia , África/epidemiologia , Animais , Humanos , Fatores de Risco , Estudos Soroepidemiológicos , Toxocara/imunologia , Toxocaríase/etiologiaRESUMO
Analysis of sequencing data for 143 blaNDM-1- and blaOXA-48-positive Klebsiella pneumoniae isolates from 13 European national collections and the public domain resulted in the identification of 15 previously undetected multi-country transmission clusters. For 10 clusters, cases had prior travel/hospitalisation history in countries outside of the European Union including Egypt, Iran, Morocco, Russia, Serbia, Tunisia and Turkey. These findings highlight the benefit of European whole genome sequencing-based surveillance and data sharing for control of antimicrobial resistance.
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Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Surtos de Doenças , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Sequenciamento Completo do Genoma/métodos , beta-Lactamases/genética , Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Carbapenêmicos/uso terapêutico , Emigração e Imigração , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana/métodosRESUMO
Between January 2018 and May 2019, 349 cases of Candida auris were reported in the European Union/European Economic Area*, 257 (73.6%) colonisations, 84 (24.1%) bloodstream infections, seven (2.0%) other infections and one case of unknown infection/colonisation status (0.3%). Most cases (97.1%, n = 339) were reported from Spain or the United Kingdom, but also for the first time in Greece, the Netherlands and Poland. Laboratory capacity and preparedness has improved since January 2018.
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Candida/isolamento & purificação , Candidíase/diagnóstico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Surtos de Doenças , Farmacorresistência Fúngica Múltipla , Europa (Continente)/epidemiologia , União Europeia , Humanos , Controle de Infecções , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: [18 F]-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (FDG-PET/CT) imaging provides important information about the size and metabolic activity of lesions caused by Echinococcus multilocularis and is therefore recommended for the initial assessment and follow-up of human alveolar echinococcosis (AE). The introduction of positron emission tomography/magnetic resonance imaging (PET/MRI) into clinical practice in affluent health care systems provides an alternative dual imaging modality, which has not yet been evaluated for AE. OBJECTIVE: Here, we describe the initial clinical experience with comparative PET/CT and PET/MR imaging in four human AE patients at an Austrian reference centre. RESULTS: PET/MR imaging showed comparable diagnostic capacity for liver lesions attributable to E. multilocularis infection, with a discrepancy only in the assessment of calcifications in one patient. Effective doses of radiation were 30.4-31 mSV for PET/CT, which were reduced in PET/MRI to the exposure of 18 F-FDG only (4.9-5.5 mSv). CONCLUSIONS: PET/MRI provides comparable diagnostic information for AE management. The reduction in radiation exposure compared to PET/CT may be of particular importance for children and young patients not amenable for curative surgery requiring repeated long-term follow-up with dual imaging modalities. Further studies are warranted to prospectively evaluate the potential of PET/MRI in the management of AE.
DONNÉES DE BASE: L'imagerie par la tomographie par émission de positrons au [18F]-2-fluoro-2-désoxy-D-glucose (18F-FDG)/tomodensitométrie (TEP/TDM) fournit des informations importantes sur la taille et l'activité métabolique des lésions causées par Echinococcus multilocularis et est donc recommandée pour l'évaluation initiale et le suivi de l'échinococcose alvéolaire (EA) humaine. L'introduction de la tomographie par émission de positons/imagerie par résonance magnétique (TEP/IRM) dans la pratique clinique des systèmes de soins de santé aisés offre une alternative de modalité d'imagerie double, qui n'a pas encore été évaluée pour l'EA. OBJECTIF: Nous décrivons ici l'expérience clinique initiale comparant les imageries TEP/TDM et TEP/IRM chez quatre patients humains atteints d'EA dans un centre de référence autrichien. RÉSULTATS: L'imagerie TEP/IRM a montré une capacité de diagnostic comparable pour les lésions hépatiques imputables à une infection à E. multilocularis, avec une divergence uniquement lors de l'évaluation des calcifications chez un patient. Les doses efficaces de rayonnement étaient de 30,4 à 31 mSV pour la TEP/TDM, qui ont été réduites dans la TEP/IRM à une exposition au 18 F-FDG uniquement (4,9 à 5,5 mSv). CONCLUSIONS: La TEP/IRM fournit des informations de diagnostic comparables pour la prise en charge de l'EA. La réduction de l'exposition aux rayonnements comparée à la TEP/TDM pourrait avoir une importance particulière pour les enfants et les jeunes patients ne pouvant pas subir de chirurgie curative nécessitant un suivi répété à long terme avec des modalités de double imagerie. Des études supplémentaires sont nécessaires pour évaluer de manière prospective le potentiel de la TEP/IRM dans la prise en charge de l'EA.
Assuntos
Equinococose/diagnóstico por imagem , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Idoso , Animais , Áustria , Feminino , Fluordesoxiglucose F18 , Humanos , Fígado/parasitologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Cystic echinococcosis (CE) is a globally occurring zoonosis, whereas alveolar echinococcosis (AE) is endemic only in certain parts of the Northern Hemisphere. The socioeconomic impact of human echinococcosis has been shown to be considerable in highly endemic regions. However, detailed data on direct healthcare-related costs associated with CE and AE are scarce for high income countries. The aim of this study was to evaluate direct costs of human disease caused by CE and AE in Austria. METHODS: Clinical data from a registry maintained at a national reference center for echinococcosis at the Medical University of Vienna were obtained for the years 2012-2014. These data were used in conjunction with epidemiological data from Austria's national disease reporting system and diagnostic reference laboratory for echinococcosis to assess nationwide costs attributable to CE and AE. RESULTS: In Austria, total modelled direct costs were 486,598 (95%CI 341,825 - 631,372) per year for CE, and 683,824 (95%CI 469,161 - 898,486) for AE. Median costs per patient with AE from diagnosis until the end of a 10-year follow-up period were 30,832 (25th- 75th percentile: 23,197 - 31,220) and 62,777 (25th- 75th percentile: 60,806 - 67,867) for inoperable and operable patients, respectively. Median costs per patients with CE from diagnosis until end of follow-up after 10 years were 16,253 (25th- 75th percentile: 8,555 - 24,832) and 1,786 (25th- 75th percentile: 736 - 2,146) for patients with active and inactive cyst stages, respectively. The first year after inclusion was the most cost-intense year in the observed period, with hospitalizations and albendazole therapy the main contributors to direct costs. CONCLUSIONS: This study provides detailed information on direct healthcare-related costs associated with CE and AE in Austria, which may reflect trends for other high-income countries. Surgery and albendazole therapy, due to surprisingly high drug prices, were identified as important cost-drivers. These data will be important for cost-effectiveness analyses of possible prevention programs.
Assuntos
Equinococose/economia , Custos de Cuidados de Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria , Criança , Países Desenvolvidos , Equinococose/tratamento farmacológico , Equinococose/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Invasive pneumococcal disease (IPD) is associated with high morbidity and mortality, with immunocompromised patients (ICPs) at particular risk. Therefore, guidelines recommend pneumococcal vaccination for these patients. However, guidelines are scarcely underpinned with references to incidence studies of IPD in this population. This, potentially results in unawareness of the importance of vaccination and low vaccination rates. The objective of this systematic review and meta-analysis was to assess the incidence of IPD in ICPs. METHODS: We systematically searched PubMed and Embase to identify studies in English published before December 6th, 2017 that included terms related to 'incidence', 'rate', 'pneumococcal', 'pneumoniae', 'meningitis', 'septicemia', or 'bacteremia'. We focused on patients with HIV, transplantation and chronic inflammatory diseases. RESULTS: We included 45 studies in the systematic review reporting an incidence or rate of IPD, defined as isolation of Streptococcus pneumoniae from a normally sterile site. Random effects meta-analysis of 38 studies showed a pooled IPD incidence of 331/100,000 person years in patients with HIV in the late-antiretroviral treatment era in non-African countries, and 318/100,000 in African countries; 696 and 812/100,000 in patients who underwent an autologous or allogeneic stem cell transplantation, respectively; 465/100,000 in patients with a solid organ transplantation; and 65/100,000 in patients with chronic inflammatory diseases. In healthy control cohorts, the pooled incidence was 10/100,000. DISCUSSION: ICPs are at increased risk of contracting IPD, especially those with HIV, and those who underwent transplantation. Based on our findings, we recommend pneumococcal vaccination in immunocompromised patients. PROSPERO REGISTRATION: ID: CRD42016048438.
Assuntos
Hospedeiro Imunocomprometido , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Adulto , África/epidemiologia , Criança , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Humanos , Incidência , Masculino , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/administração & dosagem , Fatores de Risco , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/isolamento & purificação , Transplante/efeitos adversos , VacinaçãoRESUMO
Cystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval stage of the Echinococcus granulosus sensu lato (s.l.) complex. Although the disease is known to be highly prevalent in certain parts of North and East Africa, data on CE, both in humans and definitive hosts, are extremely scarce for Central Africa. The present study assessed the epidemiology of CE in humans and dogs in rural Gabon. An ultrasound and serologic survey was conducted in volunteers from rural villages in Gabon. A two-step approach was used for serological testing with an indirect hemagglutination assay as a screening test and Western Blot as a confirmatory test. Fecal dog samples were analyzed microscopically, and polymerase chain reaction (PCR) amplification of nad1 and cox1 genes was performed when taeniid eggs were visible. Regional hospitals and the national reference center for parasitology in Gabon were contacted for information about previous cases of CE. Randomly selected communities were invited to participate. Three hundred and forty-eight human volunteers from these communities were screened. No suspected cases of CE were detected. Definitive host screening was performed from 128 fecal samples from representative subregions, but no eggs from E. granulosus s.l. were found. No documented cases of echinococcosis were reported from the local health-care institutions and the national diagnostic reference center in Gabon. Cystic echinococcosis seems to be very rare or absent in Gabon. The reason for this lack of evidence for echinococcosis is unknown, but the absence of livestock may play a major role.
Assuntos
Equinococose/epidemiologia , Adulto , Idoso , Animais , Estudos Transversais , DNA de Helmintos/análise , Cães , Equinococose/transmissão , Echinococcus granulosus/fisiologia , Monitoramento Epidemiológico , Fezes/parasitologia , Feminino , Gabão/epidemiologia , Testes de Hemaglutinação , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , População Rural , Zoonoses/epidemiologia , Zoonoses/transmissãoRESUMO
Malaria is among the major threats to global health with the main burden of disease being in rural areas of developing countries where accurate diagnosis based on non-invasive samples is in high demand. We here present a novel molecular assay for detection of malaria parasites based on technology that may be adapted for low-resource settings. Moreover, we demonstrate the exploitation of this assay for detection of malaria in saliva. The setup relies on pump-free microfluidics enabled extraction combined with a DNA sensor substrate that is converted to a single-stranded DNA circle specifically by topoisomerase I expressed by the malaria causing Plasmodium parasite. Subsequent rolling circle amplification of the generated DNA circle in the presence of biotin conjugated deoxynucleotides resulted in long tandem repeat products that was visualized colorimetrically upon binding of horse radish peroxidase (HRP) and addition of 3,3',5,5'-Tetramethylbenzidine that was converted to a blue colored product by HRP. The assay was directly quantitative, specific for Plasmodium parasites, and allowed detection of Plasmodium infection in a single drop of saliva from 35 out of 35 infected individuals tested. The results could be determined directly by the naked eye and documented by quantifying the color intensity using a standard paper scanner.
Assuntos
DNA Topoisomerases Tipo I/metabolismo , DNA/química , Malária Falciparum , Plasmodium falciparum/enzimologia , Proteínas de Protozoários/metabolismo , Saliva/metabolismo , Biomarcadores/metabolismo , Colorimetria/métodos , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/enzimologiaRESUMO
Background: Fosmidomycin-piperaquine is being developed as nonartemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance. Methods: The study was a phase 2, single-arm, proof-of-concept study of the efficacy, tolerability, and safety of fosmidomycin-piperaquine for the treatment of uncomplicated Plasmodium falciparum monoinfection in Gabon. Adults and children of both sexes with initial parasite counts between 1000 and 150000/µL received oral treatment with fosmidomycin (twice daily doses of 30 mg/kg) and piperaquine (once daily dose of 16 mg/kg) for 3 days and followed-up for 63 days. The primary efficacy endpoint was the per-protocol polymerase chain reaction (PCR)-corrected day 28 adequate clinical and parasitological response (ACPR). Results: One hundred patients were enrolled. The PCR-corrected day 28 ACPR rate was 83/83, or 100% (95% confidence interval, 96-100). Fourteen patients had asexual parasitaemia between day 28 and day 63; all were typed by PCR as new infections. Fosmidomycin-piperaquine therapy led to rapid parasite clearance (median, 36 hours; interquartile range [IQR], 6-60) and fever clearance time (median, 12 hours; IQR, 6-48). The electrocardiogram assessments showed 2 patients with prolonged QT interval >500 msec following study drug administration. The majority of adverse events affected the gastrointestinal and respiratory tracts and were transient and mild to moderate in severity. Conclusions: This is the first report of the use of the combination fosmidomycin-piperaquine. The combination appeared to have high efficacy and be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval. Clinical Trials Registration. NCT02198807.
Assuntos
Antimaláricos/uso terapêutico , Fosfomicina/análogos & derivados , Malária Falciparum/tratamento farmacológico , Quinolinas/uso terapêutico , Adolescente , Adulto , Fatores Etários , Artemisininas , Criança , Pré-Escolar , Terapia Combinada , Quimioterapia Combinada , Feminino , Fosfomicina/uso terapêutico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Reação em Cadeia da Polimerase , Estudo de Prova de Conceito , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Toxocariasis is a globally distributed zoonosis. The most important definitive hosts are dogs, whereas humans serve as paratenic hosts. Transmission to humans occurs by accidental ingestion of eggs, e.g. by consumption of contaminated fruits or vegetables. Although exposure to Toxocara is usually considered as relatively benign, it is implicated in a range of neurological, ophthalmologic and other organ-specific conditions, some of them with grave consequences. This review provides an overview on the epidemiology, presentation and risk factors of exposure to Toxocara in Africa. METHODS: A systematic search was performed for studies published after January 1st, 1990, in English, French, Portuguese, Spanish, Dutch or German. The review was prepared according to PRISMA guidelines. Studies on toxocariasis in human populations and contamination in human environments were included. RESULTS: Sixty-five papers were included. Antibodies against Toxocara spp. in humans were found to be very common across Africa. Severe manifestations have been reported mainly from North Africa. Environmental contamination including soil, vegetables and fruits sold on markets was demonstrated in various locations in Africa. CONCLUSIONS: Exposure to Toxocara is prevalent across the African continent. However, the complication frequency, the impact of the condition on the individual and the public health relevance of this zoonosis, and the economic impact have never been systematically evaluated.
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Toxocara , Toxocaríase/epidemiologia , Toxocaríase/transmissão , África/epidemiologia , Animais , Meio Ambiente , Parasitologia de Alimentos , Humanos , Prevalência , Fatores de Risco , Toxocaríase/patologiaRESUMO
BACKGROUND: The recent West African Ebola virus disease (EVD) outbreak had catastrophic impact on populations, health care systems and economies of the affected countries. Somatic symptoms have been reported to persist long beyond the acute infection. This review was conducted to provide an overview on neuro- and socio-psychological long-term sequelae of EVD survivors. METHODS: Utilizing Pubmed and PsycInfo databases, a systematic review prepared according to PRISMA guidelines. Only studies reporting quantitative data on neuropsychological sequelae three weeks or later after discharge from the Ebola-treating unit were included. Pooled proportions of common outcomes were calculated. RESULTS: In total, 224 papers were identified, of which 10 were included. Depression, insomnia, fatigue, anxiety and post-traumatic stress were common sequelae in EVD survivors. However, data from high-quality studies were scarce. CONCLUSIONS: EVD survivors have been thought to commonly face neuropsychological long-term sequelae. Methodological drawbacks and heterogeneity of current studies limit conclusions of the impact and magnitude of such sequelae. We advocate the preparation of a prospective, controlled cohort study protocol in preparation for a future outbreak.
Assuntos
Depressão , Surtos de Doenças/estatística & dados numéricos , Ebolavirus , Doença pelo Vírus Ebola , Sobreviventes , Depressão/epidemiologia , Depressão/etiologia , Fadiga/epidemiologia , Fadiga/etiologia , Doença pelo Vírus Ebola/complicações , Doença pelo Vírus Ebola/epidemiologia , Humanos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/etiologia , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricosRESUMO
Toxocara spp. are zoonotic parasites with global distribution infecting humans by incidental ingestions of eggs shed in feces of dogs or cats. High seroprevalences have been reported from several regions of Africa, however data from the Central African region remain limited. Although several clinical entities caused by larvae of Toxocara spp. have been described, the public heath impact of this infection has so far often been neglected. This study was conducted to estimate the prevalence in a rural central African population. The population based study was performed in volunteers in a rural region of Gabon. A two-step testing approach was applied using an ELISA as screening test and a Western Blot (immunoblot) as confirmatory assay. Basic demographic data and risk factors were collected and compared between seropositive and negative participants. In total, 199 out of 332 serum samples were tested positive for Toxocara spp. antibodies (59.9%). After standardization for age to the overall Gabonese population seroprevalence was 53.6% (95% CI 48.2-59.0%). There was a trend towards higher seroprevalence in participants with agricultural activity. Seroprevalence of antibodies against Toxocara spp. is high in this rural population in Gabon. These results are comparable with previous reports from other sub-regions of Africa and add to our understanding of the epidemiology of toxocariasis in Africa. Given the high prevalence of toxocariasis in tropical regions, it may be speculated that clinically relevant presentations (e.g. visceral or ocular larva migrans syndrome) may occur in considerable numbers. A formal assessment of the burden of disease and the public health impact of human toxocariasis is therefore warranted.
Assuntos
Anticorpos Anti-Helmínticos/sangue , Toxocara/isolamento & purificação , Toxocaríase/epidemiologia , Adolescente , Adulto , Idoso , Animais , Western Blotting , Gatos , Estudos Transversais , Cães , Ensaio de Imunoadsorção Enzimática , Feminino , Gabão/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Pública , População Rural , Estudos Soroepidemiológicos , Adulto JovemRESUMO
Cystic echinococcosis (CE) is a widespread zoonosis caused by the species complex Echinococcus granulosus. Albendazole (ABZ)-the first-line anthelminthic drug for medical treatment of CE-is metabolized in vivo to the active derivative ABZ-sulphoxide (ABZ-SO). Target-site ABZ-SO concentrations in the hydatid cyst mediate the anthelminthic effect in CE. Primary outcome of this systematic review of individual patient data was the intra-cystic ABZ-SO concentration stratified by cyst size, location, calcification status and use of praziquantel. Studies reporting intra-cystic ABZ-SO concentrations in humans were identified by a systematic search. A pooled analysis of individual patient data was performed to assess intra-cystic concentrations. Pharmacokinetic data of 121 individual cysts were analysed. There was no correlation between plasma and intra-cystic ABZ-SO concentrations (rho = -0.03, p = 0.76). Intra-cystic drug concentrations were also not associated with sex and treatment duration. Use of praziquantel in combination with ABZ was associated with higher plasma (median 540 vs. 240 µg/L; p = 0.04) but not intra-cystic ABZ-SO concentrations (median 220 vs. 199 µg/L; p = 0.36). Relative drug concentrations in hepatic cysts were higher than in other cysts (0.8 vs. 0.4; p = 0.05). Intra-cystic concentrations were higher in calcified than non-calcified cysts (median 897 vs. 245 µg/L; p = 0.03). There was a trend towards higher intra-cystic concentrations in smaller sized cysts (ß = -17.2 µg/L/cm; 95th CI, -35.9 to 1.6; p = 0.07). This study demonstrates that mean intra-cystic drug concentrations are similar to plasma concentrations on a population level. However, in individual patients plasma concentrations are not directly predictive for intra-cystic concentrations. The use of booster drugs was not associated with higher intra-cystic ABZ-SO concentrations in this analysis.
Assuntos
Albendazol/análogos & derivados , Anti-Helmínticos/metabolismo , Equinococose/metabolismo , Echinococcus granulosus/metabolismo , Albendazol/metabolismo , Albendazol/uso terapêutico , Animais , Anti-Helmínticos/uso terapêutico , Cistos/metabolismo , Equinococose/tratamento farmacológico , Echinococcus granulosus/efeitos dos fármacos , Humanos , Praziquantel/farmacologiaRESUMO
BACKGROUND: Cerebral malaria remains a medical emergency with high mortality. Hypo-perfusion due to obstructed blood vessels in the brain is thought to play a key role in the pathophysiology of cerebral malaria leading to neurological impairment, long-term neuro-cognitive sequelae and, potentially, death. Due to the rapid reversibility of vascular obstruction caused by sequestered Plasmodium falciparum, it is hypothesized that mild medical hypothermia--a standard intervention for other medical emergencies--may improve clinical outcome. This preclinical in vitro study was performed to assess the impact of mild hypothermia on parasite growth and the intrinsic activity of anti-malarials drugs. METHODS: Three laboratory-adapted clones and two clinical isolates were used for growth assays and standardized drug sensitivity assessments using the standard HRP2 assay. All assays were performed in parallel under normothermic (37 °C), mild hypothermic (32 °C), and hyperthermic (41 °C) conditions. RESULTS: Parasite growth was higher under standard temperature condition than under hypo- or hyperthermia (growth ratio 0.85; IQR 0.25-1.06 and 0.09; IQR 0.05-0.32, respectively). Chloroquine and mefloquine had comparable in vitro activity under mild hypothermic conditions (ratios for IC50 at 37 °C/32 °C: 0.88; 95% CI 0.25-1.50 and 0.86; 95% CI 0.36-1.36, respectively) whereas dihydroartemisinin was more active under mild hypothermic conditions (ratio for IC50 at 37 °C/32 °C: 0.27; 95% CI 0.19-0.27). Hyperthermia led by itself to almost complete growth inhibition and precluded further testing of the activity of anti-malarial drugs. CONCLUSION: This preclinical evaluation demonstrates that mild medical hypothermia inhibits in vitro growth of P. falciparum and enhances the pharmacodynamic activity of artemisinin derivatives. Based on these preclinical pharmacodynamic data, the further clinical development of mild medical hypothermia as adjunctive treatment to parenteral artesunate for cerebral malaria is warranted.
Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Cloroquina/farmacologia , Temperatura Baixa , Mefloquina/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/efeitos da radiação , Testes de Sensibilidade Parasitária , Plasmodium falciparum/crescimento & desenvolvimentoRESUMO
OBJECTIVES: On the background of a high prevalence of HHV-8 infection in pre-pubertal Central African children, this study investigated the potential for in utero transmission of HHV-8. PATIENTS: Gabonese pregnant women were invited to provide peripheral and cord blood samples for serological and PCR diagnostics of HHV-8 infection at delivery for this cross-sectional survey. RESULTS: Out of 344 participants 120 (35%, 95% CI: 30-40%) were serologically positive for HHV-8. 31% (95% CI: 22-40%) of cord blood samples of seropositive women had detectable IgG antibodies. Among all seropositive participants HHV-8 was detected by PCR in one maternal peripheral blood sample at delivery (1%, 95% CI: 0.2-7%) and in none of cord blood samples. There was no association between demographic characteristics and infection status. Similarly, there was no difference in risk for premature delivery, low birth weight, and maternal anaemia in HHV-8 seropositive women. DISCUSSION: These data suggest a high seroprevalence of HHV-8 infection in pregnant women, however viraemia at delivery does not commonly occur in Central Africa. Based on these observations it may be speculated that infection of children may occur more commonly either antepartum or later on in infancy and childhood.