RESUMO
INTRODUCTION: Norovirus outbreaks frequently occur in communities and institutional settings acquiring a particular significance in armed forces where prompt reporting is critical. Here we describe the epidemiological, clinical and laboratorial investigation of a multicentre gastroenteritis outbreak that was detected simultaneously in three Portuguese army units with a common food supplier, Lisbon region, between 5 and 6 December 2017. METHODS: Questionnaires were distributed to all soldiers stationed in the three affected army units, and stool specimens were collected from soldiers with acute gastrointestinal illness. Stool specimens were tested for common enteropathogenic bacteria by standard methods and screened for a panel of enteric viruses using a multiplex real-time PCR assay. Food samples were also collected for microbiological analysis. Positive stool specimens for norovirus were further genotyped. RESULTS: The three simultaneous acute gastroenteritis outbreaks affected a 31 (3.5%) soldiers from a total of 874 stationed at the three units and lasted for 2 days. No secondary cases were reported. Stool specimens (N=11) were negative for all studied enteropathogenic agents but tested positive for norovirus. The recombinant norovirus GII.P16-GII.4 Sydney was identified in all positive samples with 100% identity. CONCLUSIONS: The results are suggestive of a common source of infection plausibly related to the food supplying chain. Although centralisation of food supplying in the army has economic advantages, it may contribute to the multifocal occurrence of outbreaks. A rapid intervention is key in the mitigation of outbreak consequences and in reducing secondary transmission.
Assuntos
Surtos de Doenças/estatística & dados numéricos , Instalações Militares/estatística & dados numéricos , Militares/estatística & dados numéricos , Infecções por Caliciviridae/epidemiologia , Fezes/virologia , Qualidade dos Alimentos , Gastroenterite/epidemiologia , Gastroenterite/virologia , Humanos , Norovirus/efeitos dos fármacos , Norovirus/patogenicidade , Portugal/epidemiologia , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Gastrointestinal infections are among the most common foodborne and waterborne diseases in military populations, with direct implications in operational efficiency and force readiness. Through the surveillance system of reportable acute gastrointestinal illness in the Portuguese Army, four norovirus outbreaks were identified between October 2015 and October 2017 in mainland Portugal and the Azores archipelago. The present study documents the epidemiological, clinical and laboratory investigations of these norovirus outbreaks. METHODS: Cases were investigated and epidemiological questionnaires were distributed to all soldiers in each military setting where the outbreaks occurred. Stool samples from soldiers with acute gastroenteritis illness were collected and screened for common enteropathogenic agents. Food and water samples served on the settings were also collected for microbiological investigation. Norovirus-positive samples were further characterised by sequence analysis using a public automated genotyping tool. RESULTS: The four outbreaks affected a total of 99 soldiers among the 618 stationed on base units and in a military exercise. A total of 27 soldiers provided a stool sample, of which 20 were positive for norovirus by real-time PCR. Phylogenetic analysis showed that the noroviruses involved were all genogroup II, namely GII.17, GII.Pe-GII.4 Sydney 2012, GII.P2-GII.2 and GII.P16-GII.2. Of note, 30 soldiers had to receive treatment at the military hospital due to severity of symptoms. CONCLUSION: In this short, two-year surveillance period, a total of four norovirus gastroenteritis outbreaks were detected in the Portuguese Army which caused a considerable morbidity, showing once again the impact of norovirus on Army effectiveness and force readiness.
Assuntos
Infecções por Caliciviridae/epidemiologia , Gastroenterite/virologia , Militares/estatística & dados numéricos , Norovirus , Surtos de Doenças , Fezes/virologia , Gastroenterite/epidemiologia , Genótipo , Humanos , Norovirus/genética , Vigilância da População , Portugal/epidemiologiaRESUMO
AIMS: The aim of this study was to evaluate the occurrence, diversity and resistance to antibiotics of Arcobacter sp. in a dairy plant samples. METHODS AND RESULTS: A total of 75 samples from dairy plant surfaces and materials and several food products collected in different steps of the cheese production process were analysed by culture, under aerobic and microaerobic atmospheric conditions, and by enrichment molecular detection. Isolates were identified and genotyped by ERIC-PCR, and their susceptibility to nine antibiotics was evaluated by agar dilution. Global prevalence of Arcobacter sp. was 42·7%, where 20 of the 42 food samples analysed were positive for A. butzleri by both culture and molecular detection, one for A. marinus by culture and one for A. cryaerophilus by molecular detection only; 10 of the 30 analysed materials and plant surfaces were positive for A. butzleri. All A. butzleri isolates were resistant to nalidixic acid and showed high resistance rates to ampicillin (56·2%) and cefotaxime (97·9%), being all strains susceptible to gentamicin and erythromycin. CONCLUSIONS: Contamination of dairy plant environment with A. butzleri and its progression along cheese production process were observed, however, the cheese ripening process may have a relevant role in the reduction of the contamination. SIGNIFICANCE AND IMPACT OF THE STUDY: This study showed the presence of Arcobacter sp. in a dairy plant, displaying its high prevalence and genetic diversity and highlighting its high resistance rates. The data obtained could contribute to further acknowledge the Arcobacter food contamination as a potential health hazard.
Assuntos
Arcobacter/efeitos dos fármacos , Variação Genética , Animais , Antibacterianos/farmacologia , Arcobacter/genética , Arcobacter/isolamento & purificação , Queijo , Indústria de Laticínios , Resistência Microbiana a Medicamentos/genética , Contaminação de Alimentos/análise , Microbiologia de Alimentos , Genótipo , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare, genetically heterogeneous, autosomal recessive disorder. Patients suffer from recurrent infections caused by reduced levels or absence of serum immunoglobulins. Genetically, 4 subtypes of ICF syndrome have been identified to date: ICF1 (DNMT3B mutations), ICF2 (ZBTB24 mutations), ICF3 (CDCA7 mutations), and ICF4 (HELLS mutations). AIM: To study the mutation spectrum in ICF syndrome. MATERIALS AND METHODS: Genetic studies were performed in peripheral blood lymphocyte DNA from suspected ICF patients and family members. RESULTS: We describe 7 ICF1 patients and 6 novel missense mutations in DNMT3B, affecting highly conserved residues in the catalytic domain. We also describe 5 new ICF2 patients, one of them carrying a homozygous deletion of the complete ZBTB24 locus. In a meta-analysis of all published ICF cases, we observed a gender bias in ICF2 with 79% male patients. DISCUSSION: The biallelic deletion of ZBTB24 provides strong support for the hypothesis that most ICF2 patients suffer from a ZBTB24 loss of function mechanism and confirms that complete absence of ZBTB24 is compatible with human life. This is in contrast to the observed early embryonic lethality in mice lacking functional Zbtb24. The observed gender bias seems to be restricted to ICF2 as it is not observed in the ICF1 cohort. CONCLUSION: Our study expands the mutation spectrum in ICF syndrome and supports that DNMT3B and ZBTB24 are the most common disease genes.
Assuntos
Centrômero/genética , DNA (Citosina-5-)-Metiltransferases/genética , Síndromes de Imunodeficiência/genética , Proteínas Repressoras/genética , Adolescente , Adulto , Animais , Centrômero/patologia , Criança , Pré-Escolar , DNA Helicases/genética , Metilação de DNA/genética , Face/anormalidades , Face/fisiopatologia , Feminino , Predisposição Genética para Doença , Humanos , Síndromes de Imunodeficiência/fisiopatologia , Masculino , Camundongos , Mutação de Sentido Incorreto , Proteínas Nucleares/genética , Sexismo , Adulto Jovem , DNA Metiltransferase 3BRESUMO
Clostridium difficile infection (CDI) represents a great healthcare burden in developed countries. The emergence of the epidemic PCR ribotype (RT) 027 and its acquired fluoroquinolones resistance have accentuated the need for an active surveillance of CDI. Here we report the first countrywide study of CDI in Portugal with the characterization of 498 C. difficile clinical isolates from 20 hospitals in four regions in Portugal regarding RT, virulence factors and antimicrobial susceptibility. We identified 96 RTs with marked variations between and within regions, as only six RTs appeared in all four regions. RT027 was the most frequent RT overall (18.5%) and among healthcare facility-associated isolates (19.6%), while RT014 was the most common among community-associated isolates (12%). The north showed a high RT diversity among isolates and a low moxifloxacin (MXF) resistance rate (11.9%), being the only region in which RT027 was not predominant. In contrast, the isolates from the centre presented the highest RT027 frequency, and 53.4% were resistant to MXF. Overall, MXF resistance (33.2%) was associated (p <0.001) with the presence of binary toxin genes and mutations in tcdC regardless of the RT. Both traits appeared in almost 30% of the strains. RT027 showed a reduced susceptibility to metronidazole (p <0.01), and RT126 had higher minimum inhibitory concentrations to vancomycin (p = 0.03) compared to other RTs. The present study highlights an unusual heterogeneity of RTs in Portugal, with a high frequency of hypervirulent RTs and the emergence of virulence factors in non-027 RTs, emphasizing the need for a surveillance system for CDI in Portugal.
Assuntos
Clostridioides difficile/classificação , Clostridioides difficile/genética , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/microbiologia , Idoso , Antibacterianos/farmacologia , Biodiversidade , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/isolamento & purificação , Farmacorresistência Bacteriana , Feminino , Genes Bacterianos , Geografia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Vigilância da População , Portugal/epidemiologia , Fatores de Virulência/genéticaRESUMO
Prophages of Helicobacter pylori, a bacterium known to co-evolve in the stomach of its human host, were recently identified. However, their role in the diversity of H. pylori strains is unknown. We demonstrate here and for the first time that the diversity of the prophage genes offers the ability to distinguish between European populations, and that H. pylori prophages and their host bacteria share a complex evolutionary history. By comparing the phylogenetic trees of two prophage genes (integrase and holin) and the multilocus sequence typing (MLST)-based data obtained for seven housekeeping genes, we observed that the majority of the strains belong to the same phylogeographic group in both trees. Furthermore, we found that the Bayesian analysis of the population structure of the prophage genes identified two H. pylori European populations, hpNEurope and hpSWEurope, while the MLST sequences identified one European population, hpEurope. The population structure analysis of H. pylori prophages was even more discriminative than the traditional MLST-based method for the European population. Prophages are new players to be considered not only to show the diversity of H. pylori strains but also to more sharply define human populations.
Assuntos
Variação Genética , Helicobacter pylori/virologia , Prófagos/genética , Europa (Continente) , Evolução Molecular , Genes Virais , Genoma Bacteriano , Helicobacter pylori/genética , Humanos , Tipagem de Sequências Multilocus , FilogeografiaRESUMO
This report presents the results of the national surveillance system of diarrhea etiology of the National Institute of Health of Portugal concerning norovirus (NoV) during a two-year period, May 2011-2013. Of the total 580 stool samples collected from patients hospitalized for acute diarrhea in 13 Hospitals of Portugal, 67 (11.6%) tested positive for NoV. From May 2011 to March 2012 the GII.4 variant New Orleans 2009 was the most predominant strain having been replaced by the new GII.4 variant Sydney 2012 since then till the end of the survey. To our knowledge this is the first study showing the circulation of GII.4 as the norovirus strain most commonly associated to gastroenteritis and the first to report the replacement of GII.4 New Orleans by GII.4 Sydney 2012 variant in Portugal.
Assuntos
Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Diarreia/epidemiologia , Diarreia/virologia , Variação Genética , Norovirus/genética , Vigilância da População , Infecções por Caliciviridae/história , Diarreia/história , Genótipo , História do Século XXI , Hospitalização , Humanos , Norovirus/classificação , Norovirus/isolamento & purificação , Portugal/epidemiologiaRESUMO
Dientamoeba fragilis is an inhabitant of human gastrointestinal tract with a worldwide distribution. The first description considered this protozoan a rare and harmless commensal, since then it has struggled to gain recognition as a pathogen. Commercial multiplex real-time PCR was used to detect D. fragilis in fecal samples from hospitalized children (⩽18 years) with acute gastrointestinal disease, admitted to two hospitals of Lisbon area, with different demographic characteristics. A total of 176 children were studied, 103 (58·5%) male, 144 (81·8%) children between 0 and 5 years and 32 (18·2%) above 6 years old. The overall protozoa frequency considering the four tested microorganisms were 8·5% (15/176), and the most frequently found protozoan was D. fragilis, 6·3% (11/176). Dientamoeba fragilis frequency was higher among older children (21·9%), than younger children (2·8%), and greater in boys (6·8%) than in girls (5·5%). All positive children presented with diarrhoea associated with vomiting, fever and abdominal pain. Infection was associated with the age of children (P < 0·001), school attendance (P = 0·002) and consumption of certain foods (P = 0·014), e.g. cakes with crème and ham. The frequency of diantamoebiasis found in a cohort of hospitalized Portuguese children, with acute gastrointestinal disease, could be considered a very high value when compared with the protozoan frequency normally associated with this pathology.
Assuntos
Dientamoeba/isolamento & purificação , Dientamebíase/epidemiologia , Gastroenterite/epidemiologia , Dor Abdominal , Doença Aguda , Adolescente , Animais , Criança , Pré-Escolar , Estudos de Coortes , Diarreia , Dientamoeba/genética , Dientamebíase/parasitologia , Fezes/parasitologia , Feminino , Gastroenterite/parasitologia , Trato Gastrointestinal/parasitologia , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase Multiplex , Portugal/epidemiologiaAssuntos
Angioedemas Hereditários/terapia , Adolescente , Adulto , Idoso , Angioedemas Hereditários/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , América Latina , Masculino , Pessoa de Meia-IdadeRESUMO
Antibodies are an essential component of the adaptative immune response and hold long-term memory of the immunological experiences throughout life. Antibody defects represent approximately half of the well-known primary immunodeficiencies requiring immunoglobulin replacement therapy. In this article, the authors review the current indications and therapeutic protocols in the Latin American environment. Immunoglobulin replacement therapy has been a safe procedure that induces dramatic positive changes in the clinical outcome of patients who carry antibody defects.
Assuntos
Imunização Passiva/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/terapia , Guias como Assunto , Humanos , Síndromes de Imunodeficiência/imunologia , América LatinaRESUMO
Beaches worldwide provide recreational opportunities to hundreds of millions of people and serve as important components of coastal economies. Beach water is often monitored for microbiological quality to detect the presence of indicators of human sewage contamination so as to prevent public health outbreaks associated with water contact. However, growing evidence suggests that beach sand can harbor microbes harmful to human health, often in concentrations greater than the beach water. Currently, there are no standards for monitoring, sampling, analyzing, or managing beach sand quality. In addition to indicator microbes, growing evidence has identified pathogenic bacteria, viruses, and fungi in a variety of beach sands worldwide. The public health threat associated with these populations through direct and indirect contact is unknown because so little research has been conducted relating to health outcomes associated with sand quality. In this manuscript, we present the consensus findings of a workshop of experts convened in Lisbon, Portugal to discuss the current state of knowledge on beach sand microbiological quality and to develop suggestions for standardizing the evaluation of sand at coastal beaches. The expert group at the "Microareias 2012" workshop recommends that 1) beach sand should be screened for a variety of pathogens harmful to human health, and sand monitoring should then be initiated alongside regular water monitoring; 2) sampling and analysis protocols should be standardized to allow proper comparisons among beach locations; and 3) further studies are needed to estimate human health risk with exposure to contaminated beach sand. Much of the manuscript is focused on research specific to Portugal, but similar results have been found elsewhere, and the findings have worldwide implications.
Assuntos
Praias , Monitoramento Ambiental/métodos , Sedimentos Geológicos/microbiologia , Água do Mar/microbiologia , Monitoramento Ambiental/normas , Política Ambiental , Política de Saúde , Humanos , Portugal , Saúde Pública , Medição de Risco , Microbiologia da ÁguaRESUMO
AIMS: To understand whether the variability found in the proteome of Helicobacter pylori relates to the genomic methylation, virulence and associated gastric disease. METHODS AND RESULTS: We applied the Minimum-Common-Restriction-Modification (MCRM) algorithm to genomic methylation data of 30 Portuguese H. pylori strains, obtained by genome sensitivity to Type II restriction enzymes' digestion. All the generated dendrograms presented three clusters with no association with gastric disease. Comparative analysis of two-dimensional gel electrophoresis (2DE) maps obtained for total protein extracts of 10 of these strains, representative of the three main clusters, revealed that among 70 matched protein spots (in a universe of 300), 16 were differently abundant (P < 0·05) among clusters. Of these, 13 proteins appear to be related to the cagA genotype or gastric disease. The abundance of three protein species, DnaK, GlnA and HylB, appeared to be dictated by the methylation status of their gene promoter. CONCLUSIONS: Variations in the proteome profile of strains with common geographic origin appear to be related to differences in cagA genotype or gastric disease, rather than to clusters organized according to strain genomic methylation. SIGNIFICANCE AND IMPACT OF THE STUDY: The simultaneous study of the genomic methylation and proteome is important to correlate epigenetic modifications with gene expression and pathogen virulence.
Assuntos
Proteínas de Bactérias/análise , Metilação de DNA , Helicobacter pylori/genética , Proteoma/genética , Proteínas de Bactérias/genética , Análise por Conglomerados , Genoma Bacteriano , Genômica , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Humanos , Regiões Promotoras Genéticas , Proteoma/análise , Gastropatias/microbiologia , Virulência/genéticaRESUMO
El síndrome de Deleción 22q11.2 afecta el aparato cardiovascular, la inmunidad, las funciones endocrinológicas, la cavidad oral, el desarrollo neurocognitivo, con un fenotipo particular debido a una anomalía cromosómica. Objetivo: evaluar las características clínicas y citogenéticas de pacientes atendidos en forma multidisciplinaria, a través de un estudio observacional, descriptivo, transversal e interdisciplinario de una cohorte en seguimiento. Se diagnosticaron 194 pacientes con microdeleción 22q11.2, M 95/ F 99, con un rango etario: 0 a 192m (4días-16 a) y una mediana: 23m, el signo más constante fue la facies característica que se observó en un 100%, el 72,5% presentó malformación cardiovascular, 74,7% mostró defectos en su cavidad oral y el 30,5% hipoacusias. La mayoría de los pacientes evidenciaron compromiso de su neurodesarrollo en forma global, con retraso y trastorno de lenguaje. Se detectaron alteraciones en la inmunidad en el 64,31% con disminución de los linfocitos T, hipocalcemia en 36,8% y defectos urológicos en un 14,7%. Entre los diagnósticos citogenéticos se observó además dos pacientes con traslocaciones cromosómicos de novo que involucraban la microdeleción y un paciente con la deleción en mosaico. Los estudios parentales evidenciaron un 10% de casos heredados. La población estudiada mostró una clínica y frecuencia de anomalías similar a la referida en la bibliografía a excepción de los trastornos auditivos y urológicos que se vieron con menor frecuencia mientras que la prevalencia de alteraciones neurocognitivas fue mayor. La complejidad y variabilidad del síndrome requiere un manejo multidisciplinario.
22q11.2 deletion syndrome may affect the cardiovascular and immune systems, endocrine functions, the oral cavity, and neurocognitive development with a peculiar phenotype due to the chromosomal anomaly. Objective: To evaluate the clinical and cytogenetic features of patients followed-up by a multidisciplinary team in an observational, descriptive, cross-sectional and interdisciplinary cohort study. We diagnosed 194 patients with a 22q11.2 microdeletion, M 95/ F 99, with an age range of 0 to 192 months (4 days-16 years) and a me-dian age of 23 months. Characteristic facies was observed in 100% of the patients, cardiovascular malformation in 72.5%, oral cavity abnormalities in 74.7%, and hearing loss in 30.5%. The majority of the patients showed global impairment of neurological development, such as developmental delay and language disorders. Alterations in the immune system with a low T-lymphocyte count were found in 64.31% of the patients, hypocalcemia in 36.8%, and urinary abnormalities in 14.7%. Among the cytogenetic diagnoses, two patients were found to have de novo chromosome translocations involving the microdeletion and one patient had a mosaic deletion. Stud-ies in parents showed that the disease was inherited in 10% of the cases. Clinical findings and rate of anomalies in the study population were similar to those reported in the litera-ture, except for hearing loss and urinary disorders that were less frequently found, while the prevalence of neurocognitive impairment was higher. The complexity and variability of the syndrome warrants a multidisciplinay approach.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Aberrações Cromossômicas , Deleção Cromossômica , /genética , Argentina , Equipe de Assistência ao PacienteRESUMO
Primary immunodeficiency diseases (PIDD) are associated with significant morbidity and mortality and result in a significant public health burden. This is in part due to the lack of appropriate diagnosis and treatment of these patients. It is critical that governments become aware of this problem and provide necessary resources to reduce this impact on health care systems. Leading physicians in their respective countries must be supported by their own governments in order to implement tools and provide education and thus improve the diagnosis and treatment of PIDD. The Latin American Society of Primary Immunodeficiencies (LASID) has initiated a large number of activities aimed at achieving these goals, including the establishment of a PIDD registry, development of educational programmes and guidelines, and the introduction of a PIDD fellowship programme. These initiatives are positively impacting the identification and appropriate treatment of patients with PIDD in Latin America. Nevertheless, much remains to be done to ensure that every person with PIDD receives proper therapy.
Assuntos
Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Congressos como Assunto , Humanos , América Latina , Sociedades MédicasRESUMO
Early diagnosis and appropriate therapy are essential for the best prognosis and quality of life in patients with primary immunodeficiency diseases (PIDDs). Experts from several Latin American countries have been meeting on a regular basis as part of an ongoing effort to improve the diagnosis and treatment of PIDD in this region. Three programmes are in development that will expand education and training and improve access to testing facilities throughout Latin America. These programmes are: an educational outreach programme (The L-Project); an immunology fellowship programme; and the establishment of a laboratory network to expand access to testing facilities. This report provides the status of these programmes based on the most recent discussions and describes the next steps toward full implementation of these programmes.
Assuntos
Comitês Consultivos , Hispânico ou Latino , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia , Sistema de Registros , Alergia e Imunologia/educação , Bolsas de Estudo , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/epidemiologia , Testes Imunológicos/normas , América Latina , Educação de Pacientes como Assunto , Guias de Prática Clínica como Assunto , Estados UnidosRESUMO
Experts from six Latin American countries met to discuss critical issues and needs in the diagnosis and management of primary immunodeficiency diseases (PIDD). The diagnosis of PIDD is generally made following referral to an immunology centre located in a major city, but many paediatricians and general practitioners are not sufficiently trained to suspect PIDD in the first place. Access to laboratory testing is generally limited, and only some screening tests are typically covered by government health programmes. Specialised diagnostic tests are generally not reimbursed. Access to treatment varies by country reflecting differences in healthcare systems and reimbursement policies. An online PIDD Registry Programme for Latin America has been available since 2009, which will provide information about PIDD epidemiology in the region. Additional collaboration across countries appears feasible in at least two areas: a laboratory network to facilitate the diagnosis of PIDD, and educational programmes to improve PIDD awareness. In total, these collaborations should make it possible to advance the diagnosis and management of PIDD in Latin America.
Assuntos
Gerenciamento Clínico , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Alergia e Imunologia/educação , Conhecimentos, Atitudes e Prática em Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Imunoglobulinas Intravenosas/economia , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/economia , Cobertura do Seguro , Reembolso de Seguro de Saúde , América Latina , Sistema de RegistrosRESUMO
Mutations in IFNGR1, IFNGR2, IL12RB1, IL12B, STAT1 and NEMO result in a common clinical phenotype known as Mendelian Susceptibility to Mycobacterial Diseases (MSMD). Interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency is the most common genetic etiology for MSMD. Known mutations affecting IL12RB1 are recessively inherited and are associated with null response to both IL-12 and IL-23. Mutation IL12RB1 1623_1624delinsTT was originally described in 5 families from European origin (2 from Germany; 1 from Cyprus, France and Belgium). Interestingly, this same mutation was found in an unexpectedly high prevalence among IL-12Rbeta1 deficient patients in Argentina: 5-out-of-6 individuals born to unrelated families carried this particular change. To determine whether mutation 1623_1624delinsTT represents a DNA mutational hotspot or a founder effect, 34 polymorphic markers internal or proximal to IL12RB1 were studied in the Argentinean and the Belgian patients. A common haplotype spanning 1.45-3.51Mb was shared by all chromosomes carrying mutation 1623_1624delinsTT, and was not detected on 100 control chromosomes. Applying a modified likelihood-based method the age of the most recent common ancestor carrying mutation 1623_1624delinsTT was estimated in 475 years (95% CI, 175-1275), which is the time when the Spaniards initiated the colonization of the Americas. Mutation 1623_1624delinsTT represents the first founder effect described on IL-12Rbeta1, the most frequently affected gene in MSMD, and affecting patients with European ancestors. The reason(s) behind the persistency of this mutation across multiple generations, its relative high prevalence, and any potential selective advantage are yet to be established.
Assuntos
Efeito Fundador , Predisposição Genética para Doença , Infecções por Mycobacterium/genética , Receptores de Interleucina-12/genética , Animais , Argentina , Vacina BCG/administração & dosagem , Vacina BCG/efeitos adversos , Humanos , Desequilíbrio de Ligação , Modelos Genéticos , Mutação , Mycobacterium bovis/isolamento & purificação , População Branca/genéticaAssuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Rejeição de Enxerto/terapia , Imunodeficiência Combinada Severa/terapia , Saúde da Família , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Lactente , Masculino , Reoperação , Condicionamento Pré-Transplante/métodosRESUMO
Herein, we describe a combination of clinical, microbiologic, and histopathologic findings significantly associated with osteomyelitis in chronic granulomatous disease. When present, these features should raise the suspicion of underlying chronic granulomatous disease. In patients with these findings, anti-infective prophylactic measures aiming to cover highly prevalent microorganisms, as well as aggressive therapeutic measures, should be strongly encouraged.
Assuntos
Antibacterianos/uso terapêutico , Quimioprevenção , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/microbiologia , Osteomielite/microbiologia , Osteomielite/patologia , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergilose/patologia , Aspergilose/fisiopatologia , Aspergillus/isolamento & purificação , Osso e Ossos/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Doença Granulomatosa Crônica/patologia , Doença Granulomatosa Crônica/fisiopatologia , Humanos , Lactente , Micoses/tratamento farmacológico , Micoses/microbiologia , Micoses/patologia , Micoses/fisiopatologia , Osteomielite/tratamento farmacológico , Osteomielite/fisiopatologia , Penicillium/isolamento & purificação , Infecções por Serratia/tratamento farmacológico , Infecções por Serratia/microbiologia , Infecções por Serratia/patologia , Infecções por Serratia/fisiopatologia , Serratia marcescens/isolamento & purificaçãoRESUMO
Inmunoglobulina G Endovenosa UNC is a 5% liquid Argentine intravenous immunoglobulin obtained from South American donors. This prospective trial was designed to evaluate if the product meets the minimal efficacy requirement of the US Food and Drug Administration of <1 serious infection/subject/year as well as its safety in pediatric patients with Primary Immunodeficiency Diseases. Thirty patients under the age of 18, with well-defined Primary Immunodeficiency Diseases received Inmunoglobulina G Endovenosa UNC (330-700 mg/kg every 3-4 weeks) for 6 months. Vital signs, laboratory abnormalities, adverse events and viral tests were assessed to evaluate safety. Two serious infections occurred (pneumonia and bacteriemia). The estimated infection rate was 0.114 serious infection/subject/year (95% CI, 0.003-0.2277). Minor adverse events occurred in 5.5% of infusions; fever and headache were the most common. Neither severe adverse events, nor abnormal laboratory values were observed. All viral assessments were negative. Inmunoglobulina G Endovenosa UNC meets the minimal efficacy requirement of the US Food and Drug Administration for pediatric Primary Immunodeficiency Diseases patients and showed efficacy and safety data comparable with other data published.