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Antibiotic-resistant bacteria are a growing concern for human and animal health. The objective of this study was to determine the antimicrobial resistance and extended-spectrum beta-lactamase genes in Enterobacterales, Pseudomonas spp. and Acinetobacter spp. isolates from the uterus of healthy mares. For this purpose, 21 mares were swabbed for samples, which were later seeded on blood agar and MacConkey agar. The isolates were identified using MALDI-TOF and the antimicrobial susceptibility test was performed using the Kirby-Bauer technique. To characterize the resistance genes, a polymerase chain reaction (PCR) scheme was performed. Of the isolates identified as Gram-negative, 68.8% were Enterobacterales, represented by E. coli, Enterobacter cloacae, Citrobacter spp., and Klebsiella pneumoniae; 28.1% belonged to the genus Acinetobacter spp.; and 3.1% to Pseudomonas aeruginosa. A 9.3% of the isolates were multidrug-resistant (MDR), presenting resistance to antibiotics from three different classes, while 18.8% presented resistance to two or more classes of different antibiotics. The diversity of three genes that code for ESBL (blaTEM, blaCTX-M and blaSHV) was detected in 12.5% of the strains. The most frequent was blaSHV, while blaTEM and blaCTX-M were present in Citrobacter spp. and Klebsiella pneumoniae. These results are an alarm call for veterinarians and their environment and suggest taking measures to prevent the spread of these microorganisms.
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Dermatological diseases of parasitic origin are one of the most frequent in the clinical practice of dogs and cats. Mites such as Sarcoptes scabiei, Otodectes cynotis, Demodex canis, and Cheyletiella spp., commonly affect domestic dogs. However, the impact generated by these mites on populations of wildlife animals and the mechanisms involved in their epidemiological dynamics are still not clear. In recent decades, the migration of populations and their interaction with domestic environments and vice versa have generated a worrying threat due to the transmission of some of these ectoparasites. Some reports have suggested that sarcoptic mange represents an emerging threat to wildlife. Given the outbreaks of greater magnitude and geographical extension. The objective of this review is to contribute to the state of the art of the main mites that cause dermatopathies in members of the Canis lupus familiaris family and other members of the Canidae family. For this, a systematic search was carried out in the Embase and PubMed databases. Infections caused by mites, mainly scabies, continue to be diseases with a worldwide distribution, affecting mammals and humans. Although they are long-standing diseases, the effects that are generated in wild canids are still unknown. A comprehensive evaluation is required to generate guidelines in favor of the conservation of some species of foxes and wolves present in different regions of the world.
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Canidae , Doenças do Gato , Doenças do Cão , Escabiose , Animais , Cães , Humanos , Gatos , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Escabiose/epidemiologia , Escabiose/veterinária , Escabiose/parasitologia , Sarcoptes scabiei , Animais SelvagensRESUMO
Background: External otitis is common in dogs, and one of the main agents involved is Malassezia pachydermatis, a yeast belonging to the otic microbiota. Empirical treatment can fail; therefore, it is essential to know the antifungal susceptibility profile to prescribe appropriate treatment, a fact scarcely reported in Chile. Aim: This study aimed to determine the antifungal sensitivity of M. pachydermatis isolated from the external auditory canal of dogs in central Chile. Methods: Ear swabs from 30 dogs (15 healthy and 15 with external otitis) were used. Samples were subjected to cytology and fungal culture. The antifungal susceptibility was determined according to clinical and laboratory standards institute (CLSI) document M44A-2 using the disk diffusion test from amphotericin B, Caspofungin, fluconazole, nystatin, clotrimazole, and voriconazole were used. Results: The prevalence of M. pachydermatis was 66.7% from 8 healthy dogs and 12 with otitis. While fungal culture was not associated with the patient's clinical condition (p = 0.24), the yeast count by cytology was significantly higher in dogs with otitis (p = 0.003). The strains were sensitive to all antifungals except for Caspofungin, where 55% of the strains were resistant. Conclusion: Malassezia pachydermatis is isolated more frequently in dogs with otitis, and the ear cytological examination is useful to differentiate colonized dogs versus dogs with otitis. In addition, most antifungals in vitro are active against this yeast, except Caspofungin, an antifungal used in human medicine. This situation should be further monitored in epidemiological programs to evaluate the possible impact on Chilean public health.
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Dermatomicoses , Doenças do Cão , Malassezia , Otite Externa , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Caspofungina/uso terapêutico , Chile/epidemiologia , Dermatomicoses/tratamento farmacológico , Dermatomicoses/epidemiologia , Dermatomicoses/veterinária , Doenças do Cão/tratamento farmacológico , Doenças do Cão/epidemiologia , Doenças do Cão/microbiologia , Cães , Otite Externa/tratamento farmacológico , Otite Externa/epidemiologia , Otite Externa/veterinária , Saccharomyces cerevisiaeRESUMO
The close contact between people and their pets has generated the exchange of skin microbiota, accompanied by bacteria that present resistance to antibiotics. Staphylococcus spp., opportunistic pathogens present in the skin and mucosa of mammals, have had their importance recognized in human and veterinary medicine. The objectives of this study were to identify Staphylococcus spp. present in isolates from the nostrils of healthy humans, dogs and cats as well as to determine their phenotype of resistance to methicillin. Strain identification was performed by MALDI-TOF mass spectrometry and antimicrobial susceptibility was determined using a disk diffusion assay for 12 antibiotics. Sixty humans (veterinary and technicians), sixty dogs and sixty cats were sampled; of them, 61.6%, 56.6% and 46.6%, respectively, carried Staphylococcus spp. in their nostrils, and only two people carried two different species of Staphylococcus in the only anatomical site sampled. A methicillin-resistant phenotype was present in 48.7% of the humans, 26.5% of the dogs and 57.1% of the cats, and sampled. These results demonstrate the presence of Staphylococcus spp. strains resistant to methicillin in personnel who work in contact with animals, as well as in dogs and cats that entered the same hospital or veterinary clinic, which alerts us to the potential transfer of these strains to or between people, dogs and/or cats.
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Background: Culture-independent techniques have made it possible to expand the knowledge about the composition of bacterial communities present in the healthy uterus and their role in health and disease, mainly in humans. However, in animals like mares, there is a dearth of information regarding this area. Aim: To narrow this knowledge gap, the objective of this study was to identify and characterize the composition and function of the uterine microbiome of a group of Chilean purebred mares (CPM), an equine breed with the oldest genealogical record in South America and an economical important reproductive industry. Methods: From uterine biopsy samples obtained during estrus, DNA extraction and targeted sequencing were performed to investigate the bacterial diversity and its probable metabolic function. Results: CPM biopsy samples were characterized by having a varied microbial composition, where the four most relatively abundant phyla were Proteobacteria (69.6%), Firmicutes (21.1%), Bacteroidetes (7.8%), and Actinobacteria (1.06%); which made up 99.6% of the total identified phyla. In contrast, Actinobacteria and Fusobacteria were the phyla not identified in all samples. Of a total of 59 genera identified across all samples, Staphylococcus was the most abundant genus with an average relative abundance of 18.88%, followed by Pseudomonas (17.9%), Escherichia/Shigella (10.42%), and Klebsiella (9.92%). Conclusion: These findings contribute to the knowledge of microbes' presence in the uterus, while future studies are required to demonstrate the role of these microorganisms in health and disease.
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Actinobacteria , Microbiota , Útero , Animais , Feminino , Humanos , Actinobacteria/genética , Bactérias/genética , Firmicutes/genética , Cavalos , Redes e Vias Metabólicas , Microbiota/genética , Útero/microbiologiaRESUMO
Abstract In Paraguay, neonatal screening for congenital hypothyroidism (CH) and phenylketonuria (PKU) started in October 1999, in 2005 cystic fibrosis (CF) was selectively incorporated. The National Program for Neonatal Screening has a centralized laboratory that encompasses 1.132 Sample Collecting Sites (SCS) distributed in the 18 Health Regions, with over 80% coverage of live births; the incidence of CH being 1:2.060, HPA/PKU 1:6.328 and CF 1:5.671 newborns. The newborn screening program headed by the Ministry of Public Health and Social Welfare in Paraguay has been consolidated itself as a public health program. This publication describes the historic 20-year process, the strategies and activities carried out as well as the results and achievements, among which it is important to point out the achievement of newborns screening laws that make mandatory to detect, diagnose and treat those affected, as well as the human resources committed to newborn screening.
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BACKGROUND: Paedeatric Zika remains an understudied topic. WHO and the Pan American Health Organization (PAHO) Zika case definitions have not been assessed in children. We aimed to characterise clinical profiles and evaluate the diagnostic performance of the WHO and PAHO case definitions in a large cohort of paediatric Zika cases. METHODS: From January, 2016 to February, 2017, encompassing the major 2016 Zika epidemic, participants in the Pediatric Dengue Cohort Study (PDCS) in Managua, Nicaragua, were encouraged to visit the study health centre at first indication of any illness. PDCS participants were aged 2-14 years, healthy at enrolment, and recruited before the initiation of the present study. Molecular and serological assays were used to test participants exhibiting any of four broad clinical profiles suspected of resulting from a symptomatic Zika virus infection. These clinical profiles were: fever and at least two of headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic manifestations, and leukopenia; fever and at least two of nausea or vomiting, rash, aches and pains, positive tourniquet test, leukopenia, and any dengue warning sign; undifferentiated fever without evident cause, with or without any other clinical finding; and afebrile rash with or without any other clinical finding. We characterised acute clinical findings (signs, symptoms, and complete blood counts) in both Zika cases and non-Zika cases. FINDINGS: We prospectively followed a cohort of about 3700 children, of which 1110 were deemed eligible for inclusion. Four participants with laboratory-confirmed Zika (three co-infections with dengue virus, one missing complete blood count data) and two participants who were non-Zika cases (missing complete blood count data) were excluded from analysis. We analysed 556 laboratory-confirmed Zika and 548 non-Zika cases. The WHO case definition captured 176 confirmed Zika cases, and the PAHO definition 109 confirmed Zika cases, who presented with the most clinical findings and a dengue-like clinical profile. The remaining two thirds of Zika cases, principally characterised by undifferentiated fever or afebrile rash, were missed. Among Zika cases, rash (n=440)-particularly generalised erythematous rash (n=334)-fever (n=333), leukopenia (n=217), and headache (n=203) were most common and peaked within 3 days of illness onset. The most common Zika presentation over the first week of illness was rash only (n=80). The sensitivity of Zika case definitions increased across paediatric age (from 11·3% to 56·1% for the WHO case definition and from 6·0% to 36·6% for the PAHO case definition), as the prevalence of most clinical findings (particularly arthralgia) increased with age, irrespective of previous dengue virus infection. Consequently, Zika manifested differently across paediatric age; older Zika cases presented with a dengue-like clinical profile while younger Zika cases presented with undifferentiated fever or afebrile rash. INTERPRETATION: We provide the most thorough description of paediatric Zika to date. Most paediatric Zika cases go undetected under the WHO and PAHO case definitions, suggesting that current standards for Zika case ascertainment require revision. Zika manifests with mild but differing clinical profiles across paediatric age, presenting major challenges to diagnosis, surveillance, and efforts to control future Zika epidemics. FUNDING: US National Institutes of Health.
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Regras de Decisão Clínica , Infecção por Zika virus/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Técnicas de Diagnóstico Molecular , Nicarágua , Estudos Prospectivos , Sensibilidade e Especificidade , Testes Sorológicos , Infecção por Zika virus/diagnósticoRESUMO
Health research on tourism has expanded over the past two decades, focusing on understanding how the social, economic, and political configuration of tourism zones might contribute to health vulnerabilities among the diverse populations that interact in these areas. While there are few studies of HIV and drug use interactions in the region, research has indicated that these two outcomes are often interwoven in tourism zones, potentially producing 'syndemics' of HIV infection and problematic drug use. One framework that has been used in public health research on tourism is one that we refer to as touristic escapism or situational disinhibition that may be heightened for some tourists while on vacation, potentially leading to the abandonment of normative constraints on behaviour and contributing to health risks such as unprotected sex or binge drinking. In this article, we draw upon tourism theory and ethnographic research with male tourism workers employed in two popular tourist areas of the Dominican Republic to explore whether touristic escapism offers insights in understanding health vulnerabilities within tourism spaces.
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Infecções por HIV , Determinantes Sociais da Saúde , Viagem , Antropologia Cultural , República Dominicana , Emprego , Humanos , Masculino , Populações VulneráveisRESUMO
Introducción: Fibrosis quística (FQ) patología genética, autosómica recesiva por mutaciones en el gen de la proteína reguladora de la conductancia transmembrana (CFTR cystic fibrosis transmembrane regulator). En una enfermedad multisistémica, afecta el aparato respiratorio, sistema digestivo, glándulas sudoríparas y conducto deferente. En Paraguay la detección, diagnóstico y tratamiento es obligatoria y gratuita para todo recién nacidos (RN). El tamizaje neonatal es realizado a través del dosaje de la tripsinainmuno reactiva (TIR) y la confirmación diagnóstica con el test del sudor. Objetivo: Reportar la incidencia de la FQ en la población de RN de Paraguay. Es un Materiales y Métodos: trabajo descriptivo, retrospectivo de corte trasversal, donde se analizaron los datos del Programa Nacional de Detección Neonatal (PNDN), de enero del 2015 a diciembre del 2017, para el análisis de la base de datos se utilizó una planilla Excel. Resultados: En el 2015 un 91% (79.093/87.181) de las muestras ingresadas al Programa reunieron los criterios (edad y calidad de la muestra) para el estudio de la TIR, arrojando una incidencia de 1 en 6.591 RN. Para el 2016, esto correspondió a un 97% (83.525/86.094) con una incidencia de 1 en 4.176 RN y por último en el 2017, se tuvo un 97% (87.075/90.037) con una incidencia de 1 en 5.112 RN. Conclusión: La incidencia de la FQ en la población de recién nacidos del Paraguay, en los tres años que abarca este estudio, no presentan entre sí diferencias significativas, tampoco con las reportadas para la población hispánica.
Introduction: Cystic fibrosis (CF), is an autosomal recessive genetic pathology that is caused by mutations in the transmembrane conductance regulatory protein (CFTR cystic fibrosis transmembrane regulator) gene. As a multisystem disease, it affects the respiratory system, digestive system, sweat glands and vas deferens. In Paraguay, detection, diagnosis and treatment is mandatory and free for all newborns (NB). Neonatal screening is performed by the immunoreactive trypsinogen assay (IRT) and diagnostic confirmation is performed by the sweat test. Objective: To report the incidence of CF in the NB population of Paraguay. Materials and Methods: This was a descriptive, retrospective, cross-sectional study, where data from the National Neonatal Screening Program (NNSP) were analyzed, from January 2015 to December 2017. To analyze the database, we used an Excel spreadsheet. Results: In 2015, 91% (79,093 / 87,181) of the samples sent to the Program met the criteria (age and sample quality) for the IRT study, with an incidence of 1 in 6,591 NB. In 2016, 97% (83,525 / 86,094) met criteria, with an incidence of 1 in 4,176 NB, while in 2017, 97% (87,075 / 90,037) met criteria, with an incidence of 1 in 5,112 NB. Conclusion: The incidence of CF in the newborn population of Paraguay, during the three years of this study, did not show significant differences between years, nor with those reported for the Hispanic population.
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Dengue virus (DENV) is the most prevalent human vector-borne viral disease. The force of infection (FoI), the rate at which susceptible individuals are infected in a population, is an important metric for infectious disease modeling. Understanding how and why the FoI of DENV changes over time is critical for developing immunization and vector control policies. We used age-stratified seroprevalence data from 12 years of the Pediatric Dengue Cohort Study in Nicaragua to estimate the annual FoI of DENV from 1994 to 2015. Seroprevalence data revealed a change in the rate at which children acquire DENV-specific immunity: in 2004, 50% of children age >4 years were seropositive, but by 2015, 50% seropositivity was reached only by age 11 years. We estimated a spike in the FoI in 1997-1998 and 1998-1999 and a gradual decline thereafter, and children age <4 years experienced a lower FoI. Two hypotheses to explain the change in the FoI were tested: (i) a transition from introduction of specific DENV serotypes to their endemic transmission and (ii) a population demographic transition due to declining birth rates and increasing life expectancy. We used mathematical models to simulate these hypotheses. We show that the initial high FoI can be explained by the introduction of DENV-3 in 1994-1998, and that the overall gradual decline in the FoI can be attributed to demographic shifts. Changes in immunity and demographics strongly impacted DENV transmission in Nicaragua. Population-level measures of transmission intensity are dynamic and thus challenging to use to guide vaccine implementation locally and globally.
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Anticorpos Antivirais/sangue , Vírus da Dengue/isolamento & purificação , Dengue/epidemiologia , Dengue/transmissão , Estudos Soroepidemiológicos , Adolescente , Criança , Pré-Escolar , Dengue/virologia , Feminino , Humanos , Masculino , Nicarágua/epidemiologia , Estudos Prospectivos , Vigilância em Saúde Pública , Fatores de TempoRESUMO
Zika virus (ZIKV) infection recently caused major epidemics in the Americas and is linked to congenital birth defects and Guillain-Barré Syndrome. A pilot study of ZIKV infection in Nicaraguan households was conducted from August 31 to October 21, 2016, in Managua, Nicaragua. We enrolled 33 laboratory-confirmed Zika index cases and their household members (109 contacts) and followed them on days 3-4, 6-7, 9-10, and 21, collecting serum/plasma, urine, and saliva specimens along with clinical, demographic, and socio-economic status information. Collected samples were processed by rRT-PCR to determine viral load (VL) and duration of detectable ZIKV RNA in human bodily fluids. At enrollment, 11 (10%) contacts were ZIKV rRT-PCR-positive and 23 (21%) were positive by IgM antibodies; 3 incident cases were detected during the study period. Twenty of 33 (61%) index households had contacts with ZIKV infection, with an average of 1.9 (range 1-6) positive contacts per household, and in 60% of these households, ≥50% of the members were positive for ZIKV infection. Analysis of clinical information allowed us to estimate the symptomatic to asymptomatic (S:A) ratio of 14:23 (1:1.6) among the contacts, finding 62% of the infections to be asymptomatic. The maximum number of days during which ZIKV RNA was detected was 7 days post-symptom onset in saliva and serum/plasma and 22 days in urine. Overall, VL levels in serum/plasma, saliva, and urine specimens were comparable, with means of 5.6, 5.3 and 4.5 log10 copies/ml respectively, with serum attaining the highest VL peak at 8.1 log10 copies/ml. Detecting ZIKV RNA in saliva over a similar time-period and level as in serum/plasma indicates that saliva could potentially serve as a more accessible diagnostic sample. Finding the majority of infections to be asymptomatic emphasizes the importance of silent ZIKV transmission and helps inform public health interventions in the region and globally.
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Anormalidades Congênitas/etiologia , Síndrome de Guillain-Barré/etiologia , Infecção por Zika virus/epidemiologia , Zika virus/isolamento & purificação , Adolescente , Adulto , Idoso , Doenças Assintomáticas , Criança , Pré-Escolar , Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/virologia , Características da Família , Feminino , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/virologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nicarágua/epidemiologia , Projetos Piloto , RNA Viral/sangue , RNA Viral/urina , Saliva/virologia , Carga Viral , Adulto Jovem , Zika virus/genética , Zika virus/imunologia , Infecção por Zika virus/complicações , Infecção por Zika virus/virologiaRESUMO
Zika virus (ZIKV) is a mosquito-borne flavivirus that is responsible for recent explosive epidemics in the Americas. Notably, ZIKV infection during pregnancy has been found to cause congenital birth defects, including microcephaly, and ZIKV has been associated with Guillain-Barré syndrome in adults. Diagnosis and surveillance of Zika in the Americas have been challenging due to similar clinical manifestations and extensive antibody cross-reactivity with endemic flaviviral diseases, such as dengue. We evaluated four serological and two reverse transcription-PCR (RT-PCR) methods in acute-phase (mean day, 1.8), early-convalescent-phase (mean day, 16.7), and late-convalescent-phase (mean, ~7 months) samples from the same individuals in a long-term pediatric cohort study in Nicaragua. Well-characterized samples from 301 cases of Zika, dengue, or non-Zika, nondengue febrile illnesses were tested. Compared to a composite reference, an in-house IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and the NIAID-Biodefense and Emerging Infections (BEI) MAC-ELISA measuring IgM yielded sensitivities of 94.5% and 70.1% and specificities of 85.6% and 82.8%, respectively. The NS1 blockade-of-binding ELISA measuring anti-ZIKV NS1 antibody levels yielded sensitivities of 85.0% and 96.5% and specificities of 91.4% and 92.6% at early and late convalescence, respectively. An inhibition ELISA detecting total anti-ZIKV antibodies had sensitivity and specificity values of 68.3% and 58.3% for diagnosis and 94.0% and 98.6% for measuring annual infection incidence. Finally, the ZCD and Trioplex real-time RT-PCR assays detecting Zika, chikungunya, and dengue viruses both yielded a sensitivity of 96.1% and specificity of 100%. Together, these assays resolve the urgent need for diagnostic and surveillance tools for countries affected by Zika virus infections.
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Monitoramento Epidemiológico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Testes Sorológicos/normas , Infecção por Zika virus/diagnóstico , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Reações Cruzadas , Dengue/diagnóstico , Dengue/epidemiologia , Vírus da Dengue/genética , Vírus da Dengue/imunologia , Vírus da Dengue/isolamento & purificação , Ensaio de Imunoadsorção Enzimática/normas , Feminino , Humanos , Nicarágua/epidemiologia , Sensibilidade e Especificidade , Zika virus/genética , Zika virus/imunologia , Infecção por Zika virus/epidemiologiaRESUMO
BACKGROUND: Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) cocirculate in Nicaragua. In this study, we sought to compare the quantified viremia and clinical presentation of patients infected with 1 or more of these viruses. METHODS: Acute-phase serum samples from 346 patients with a suspected arboviral illness were tested using a multiplex real-time reverse-transcription polymerase chain reaction for ZIKV, CHIKV, and DENV. Viremia was quantitated for each detected virus, and clinical information from request forms submitted with each sample was recorded. RESULTS: A total of 263 patients tested positive for 1 or more viruses: 192 patients tested positive for a single virus (monoinfections) and 71 patients tested positive for 2 or all 3 viruses (coinfections). Quantifiable viremia was lower in ZIKV infections compared with CHIKV or DENV (mean 4.70 vs 6.42 and 5.84 log10 copies/mL serum, respectively; P < .001 for both comparisons), and for each virus, mean viremia was significantly lower in coinfections than in monoinfections. Compared with patients with CHIKV or DENV, ZIKV patients were more likely to have a rash (P < .001) and less likely to be febrile (P < .05) or require hospitalization (P < .001). Among all patients, hospitalized cases had higher viremia than those who did not require hospitalization (7.1 vs 4.1 log10 copies/mL serum, respectively; P < .001). CONCLUSIONS: ZIKV, CHIKV, and DENV result in similar clinical presentations, and coinfections may be relatively common. Our findings illustrate the need for accurate, multiplex diagnostics for patient care and epidemiologic surveillance.
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Febre de Chikungunya/virologia , Dengue/virologia , Viremia , Infecção por Zika virus/virologia , Adulto , Febre de Chikungunya/complicações , Febre de Chikungunya/fisiopatologia , Coinfecção , Dengue/complicações , Dengue/fisiopatologia , Feminino , Humanos , Masculino , Nicarágua , Viremia/fisiopatologia , Viremia/virologia , Adulto Jovem , Infecção por Zika virus/complicações , Infecção por Zika virus/fisiopatologiaRESUMO
Dengue virus (DENV) is a flavivirus of worldwide importance, with approximately 4 billion people across 128 countries at risk of infection, and up to 390 million infections and 96 million clinically apparent cases estimated annually. Previous in vitro studies have shown that lipids and lipoproteins play a role in modifying virus infectivity. However, the relationship between development of severe dengue and total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, is unclear. We analyzed data from 789 laboratory-confirmed dengue cases and 447 other febrile illnesses (OFI) in a prospective pediatric hospital-based study in Managua, Nicaragua between August 2005 and January 2013, using three different classifications of dengue severity: World Health Organization (WHO) 1997, WHO 2009, and standardized intervention categories. Total serum cholesterol and LDL-C levels decreased over the course of illness and were generally lower with increasing dengue severity, regardless of classification scheme. Greater decreases in LDL-C than HDL-C were observed among dengue-positive patients compared to patients with OFI and among severe dengue compared to mild dengue cases. Furthermore, daily cholesterol levels declined with daily albumin blood levels. To examine the effect of cholesterol at presentation on subsequent risk of development of severe dengue, relative risks and 95% confidence intervals were calculated using multivariable modified Poisson models. We found that lower total serum cholesterol and LDL-C levels at presentation were associated with subsequent risk of developing dengue hemorrhagic fever/dengue shock syndrome using the WHO 1997 dengue severity classification, and thus that the reduction in LDL-C is likely driving the decreases observed in total serum cholesterol levels among dengue-positive patients. Our results suggest that cholesterol blood levels are important correlates of dengue pathophysiology and should be explored as part of a prognostic biomarker panel for severe dengue.
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LDL-Colesterol/sangue , Dengue Grave/epidemiologia , Dengue Grave/patologia , Biomarcadores/sangue , Pré-Escolar , HDL-Colesterol/sangue , Feminino , Humanos , Lactente , Masculino , Nicarágua/epidemiologia , Prognóstico , Estudos Prospectivos , Medição de RiscoRESUMO
BACKGROUND: In January 2005, Rasulov et al. originally published "First experience in the use of bone marrow mesenchymal stem cells (MSCs) for the treatment of a patient with deep skin burns". Here, we present the first ever treated patient with cadaveric bone marrow mesenchymal stem cells (CMSCs) in the history of Medicine. METHODS: A young man, who severely burned 60 % of his total body surface with 30 % of full-thickness burns while working with a grass trimmer that exploded, was involved in the study. MSCs were obtained from the bone marrow of a cadaver donor in a routine procurement procedure of CUCAIBA, the Province of Buenos Aires, Argentina, Ministry of Health, Transplantation Agency, cultured, expanded, and applied on the burned surfaces using a fibrin spray after early escharotomy. RESULTS: So far, our preliminary experience and our early results have been very impressive showing an outstanding safety data as well as some impressive good results in the use of CMSCs. CONCLUSIONS: Based on all this, we think that improvements in the use of stem cells for burns might be possible in the near future and a lot of time as well as many lives could be saved by many other research teams all over the world. CMSCs will probably be a real scientific opportunity in Regenerative Medicine as well as in Transplantation.
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Analogous to observations in RNA viruses such as human immunodeficiency virus, genetic variation associated with intrahost dengue virus (DENV) populations has been postulated to influence viral fitness and disease pathogenesis. Previous attempts to investigate intrahost genetic variation in DENV characterized only a few viral genes or a limited number of full-length genomes. We developed a whole-genome amplification approach coupled with deep sequencing to capture intrahost diversity across the entire coding region of DENV-2. Using this approach, we sequenced DENV-2 genomes from the serum of 22 Nicaraguan individuals with secondary DENV infection and captured â¼75% of the DENV genome in each sample (range, 40 to 98%). We identified and quantified variants using a highly sensitive and specific method and determined that the extent of diversity was considerably lower than previous estimates. Significant differences in intrahost diversity were detected between genes and also between antigenically distinct domains of the Envelope gene. Interestingly, a strong association was discerned between the extent of intrahost diversity in a few genes and viral clade identity. Additionally, the abundance of viral variants within a host, as well as the impact of viral mutations on amino acid encoding and predicted protein function, determined whether intrahost variants were observed at the interhost level in circulating Nicaraguan DENV-2 populations, strongly suggestive of purifying selection across transmission events. Our data illustrate the value of high-coverage genome-wide analysis of intrahost diversity for high-resolution mapping of the relationship between intrahost diversity and clinical, epidemiological, and virological parameters of viral infection.
Assuntos
Vírus da Dengue/classificação , Vírus da Dengue/genética , Dengue/virologia , Variação Genética , Genoma Viral , Adolescente , Criança , Análise por Conglomerados , Estudos de Coortes , Vírus da Dengue/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Dados de Sequência Molecular , Nicarágua , Filogenia , Estudos Prospectivos , RNA Viral/genéticaRESUMO
Dengue is a major public health problem worldwide and continues to increase in incidence. Dengue virus (DENV) infection leads to a range of outcomes, including subclinical infection, undifferentiated febrile illness, Dengue Fever (DF), life-threatening syndromes with fluid loss and hypotensive shock, or other severe manifestations such as bleeding and organ failure. The long-standing World Health Organization (WHO) dengue classification and management scheme was recently revised, replacing DF, Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) with Dengue without Warning Signs, Dengue with Warning Signs (abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing hematocrit with decreasing platelets) and Severe Dengue (SD; dengue with severe plasma leakage, severe bleeding, or organ failure). We evaluated the traditional and revised classification schemes against clinical intervention levels to determine how each captures disease severity using data from five years (2005-2010) of a hospital-based study of pediatric dengue in Managua, Nicaragua. Laboratory-confirmed dengue cases (nâ=â544) were categorized using both classification schemes and by level of care (I-III). Category I was out-patient care, Category II was in-patient care that did not meet criteria for Category III, which included ICU admission, ventilation, administration of inotropic drugs, or organ failure. Sensitivity and specificity to capture Category III care for DHF/DSS were 39.0% and 75.5%, respectively; sensitivity and specificity for SD were 92.1% and 78.5%, respectively. In this data set, DENV-2 was found to be significantly associated with DHF/DSS; however, this association was not observed with the revised classification. Among dengue-confirmed cases, the revised WHO classification for severe dengue appears to have higher sensitivity and specificity to identify cases in need of heightened care, although it is no longer as specific for a particular pathogenic entity as was the traditional schema.
Assuntos
Dengue/diagnóstico , Dengue/patologia , Índice de Gravidade de Doença , Adolescente , Criança , Pré-Escolar , Dengue/complicações , Feminino , Humanos , Lactente , Masculino , Nicarágua , Sensibilidade e Especificidade , Choque/diagnóstico , Choque/patologia , Organização Mundial da SaúdeRESUMO
The four dengue virus serotypes (DENV1-4) cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric dengue in Managua. From August 2009-January 2010, 212 dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 dengue cases were recorded in 2009-10, compared to 13-65 cases in 2004-9. In both studies, significantly more patients experienced "compensated shock" (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse) in 2009-10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p<0.001) and 17% [29/170] vs. 2.2% [4/181] in the cohort study (p<0.001). Signs of poor peripheral perfusion presented significantly earlier (1-2 days) in 2009-10 than in previous years according to Kaplan-Meier survival analysis. In the hospital study, 19.8% of subjects were transferred to intensive care, compared to 7.1% in previous years - similar to the cohort study. DENV-3 predominated in 2008-9, 2009-10, and 2010-11, and full-length sequencing revealed no major genetic changes from 2008-9 to 2010-11. In 2008-9 and 2010-11, typical dengue was observed; only in 2009-10 was unusual presentation noted. Multivariate analysis revealed only "2009-10" as a significant risk factor for Dengue Fever with Compensated Shock. Interestingly, circulation of pandemic influenza A-H1N1 2009 in Managua was shifted such that it overlapped with the dengue epidemic. We hypothesize that prior influenza A H1N1 2009 infection may have modulated subsequent DENV infection, and initial results of an ongoing study suggest increased risk of shock among children with anti-H1N1-2009 antibodies. This study demonstrates that parameters other than serotype, viral genomic sequence, immune status, and sequence of serotypes can play a role in modulating dengue disease outcome.
Assuntos
Vírus da Dengue/classificação , Vírus da Dengue/isolamento & purificação , Dengue/epidemiologia , Dengue/patologia , Surtos de Doenças , Choque/epidemiologia , Adolescente , Criança , Pré-Escolar , Dengue/complicações , Dengue/virologia , Vírus da Dengue/genética , Feminino , Humanos , Lactente , Masculino , Nicarágua/epidemiologia , RNA Viral/genética , Análise de Sequência de DNA , SorotipagemRESUMO
Here we report on 4 hospitalized patients with dengue-influenza virus coinfections. All patients were RT-PCR positive for dengue virus and pandemic influenza A H1N1. Clinical findings at presentation ranged from influenza-like illness to severe dengue. Clinical progression of the infections varied, but all developed dengue symptoms and had interstitial infiltrates. Three cases required intensive care management and 1 case was fatal.