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1.
Science ; 361(6404): 810-813, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-30026316

RESUMO

RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system.


Assuntos
Artrite/genética , Doenças Inflamatórias Intestinais/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Imunodeficiência Combinada Severa/genética , Alelos , Artrite/imunologia , Citocinas/metabolismo , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Doenças Inflamatórias Intestinais/imunologia , Linfopenia/genética , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Linhagem , Imunodeficiência Combinada Severa/imunologia
2.
PLoS One ; 13(5): e0197662, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29799873

RESUMO

Prevalence and molecular epidemiology studies for hepatitis B (HBV) and C (HCV) virus are scarce in Warao Amerindians from Venezuela, where an epidemic of human immunodeficiency virus type 1 (HIV-1) has recently been documented. To carry out a molecular epidemiology analysis of hepatitis B (HBV) and C (HCV) virus in Warao individuals from the Delta Amacuro State of Venezuela. A total of 548 sera were tested for serological and molecular markers for HBV and HCV. The prevalence of active infection (presence of HBV surface antigen, HBsAg), exposure to HBV (presence of Antibody to HBV core antigen, anti-HBc) and anti-HCV, was 1.8%, 13% and 0% respectively. HBV exposure was significantly lower in men below 18 years old and also lower than rates previously reported in other Amerindian communities from Venezuela. Thirty one percent (31%, 25/80) of individuals without evidence of HBV infection exhibited anti-HBs titer ≥ 10U.I / ml, being significantly more frequent in individuals younger than 20 years. A higher HBV exposure was observed among HIV-1 positive individuals (33% vs 11%, p <0.005). A high prevalence of occult HBV infection was also observed (5.6%, 11/195). Phylogenetic analysis of S gene and complete HBV genomes showed that F3 is the only circulating subgenotype, different from the F2 subgenotype found in 1991 in this population. These results suggest a recent introduction of subgenotype F3, with a low divergence among the isolates. These results highlight the importance of molecular epidemiology studies for viral control, and support the effectiveness of vaccination in reducing transmission of HBV.

4.
AIDS Res Hum Retroviruses ; 31(12): 1265-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26414846

RESUMO

We previously reported a high prevalence of HIV-1 infection in Warao Amerindians from Venezuela due to the rapid spread of a single B subtype strain. In this study we evaluated the coreceptor use of the HIV-1 strains infecting this Amerindian community. Sequences of the HIV-1 V3 loop from 56 plasma samples were genotyped for coreceptor use. An extremely high frequency of CXCR4 strains was found among HIV-1-infecting Waraos (47/49, 96%), compared to HIV-1 strains infecting the non-Amerindian Venezuelan population (35/79, 44%, p < 0.00001). Evolutionary analysis showed that a significant number of infections occurred between 1 and 12 months before collection and that a great proportion (50-70%) of HIV-1 transmissions occurred within the very early phase of infection (≤12 months). This is consistent with an initial infection dominated by an X4 strain or a very rapid selection of X4 variants after infection. This Amerindian population also exhibits the highest prevalence of tuberculosis in Venezuela, being synergistically bad prognostic factors for the evolution of morbidity and mortality in this vulnerable population.


Assuntos
Epidemias , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Receptores CXCR4/metabolismo , Receptores de HIV/metabolismo , Feminino , Genótipo , Proteína gp120 do Envelope de HIV/genética , HIV-1/isolamento & purificação , HIV-1/fisiologia , Humanos , Índios Centro-Americanos , Masculino , Plasma/virologia , Análise de Sequência de DNA , Venezuela/epidemiologia
5.
Nat Genet ; 47(5): 523-527, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25774636

RESUMO

Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10(-11) for rs4733781; P = 1.0 × 10(-10) for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis-infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Células Dendríticas/fisiologia , Tuberculose Pulmonar/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Estudos de Casos e Controles , Movimento Celular , Células Cultivadas , Feminino , Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Transporte Proteico
6.
Invest. clín ; 55(4): 332-351, dic. 2014. ilus, tab
Artigo em Inglês | LILACS | ID: lil-783088

RESUMO

Sucre municipality is a large, densely populated marginal area in the eastern part of Caracas, Venezuela that consistently has more cases of tuberculosis than other municipalities in the country. To identify the neighborhoods in the municipality with the highest prevalence of tuberculosis, and determine whether the Mycobacterium tuberculosis strain distribution in this municipality is different from that previously found in the western part of Caracas and the rest of Venezuela, we collected data on all tuberculosis cases in the municipality diagnosed in 2005-6. We performed two separate molecular epidemiological studies, spoligotyping 44 strains in a first study, and spoligotyping 131 strains, followed by MIRU-VNTR 15 on 21 clustered isolates in the second. With spoligotyping, the most common patterns were Shared International Type SIT17 (21%); SIT42 (15%); SIT93 (11%); SIT20 (7%); SIT53 (6%), a distribution similar to other parts of Venezuela, except that SIT42 and SIT20 were more common. MIRU-VNTR 15 showed that six of seven SIT17 strains examined belonged to a large cluster previously found circulating in Venezuela, but all of the SIT42 strains were related to a cluster centered in the neighborhoods of Unión and Maca, with a MIRU-VNTR pattern not previously seen in Venezuela. It appears that a large percentage of the tuberculosis in the Sucre municipality is caused by the active transmission of two strain families centered within distinct neighborhoods, one reflecting communication with the rest of the country, and the other suggesting the insular, isolated nature of some sectors.


El municipio Sucre es un área densamente poblada del este de Caracas, Venezuela, con más casos de tuberculosis que otros municipios del país. Para establecer las áreas en el municipio Sucre con la mas alta prevalencia de tuberculosis y determinar sí la distribución de cepas de Mycobacterium tuberculosis es diferente de las encontradas previamente en el Oeste de Caracas y el resto de Venezuela, se recolectaron los datos de todos los casos diagnosticados de tuberculosis en el municipio en el 2005-6. Además, se aplicaron dos estudios de epidemiología molecular, el primero con 44 aislados en 2006 y el segundo con 131 aislados del 2006 al 2011, todos caracterizados por spoligotyping. Fue aplicada la técnica MIRU VNTR15 sobre 21 aislados agrupados. Con spoligotyping, los patrones encontrados fueron SIT17 (21%); SIT42 (15%); SIT93 (11%); SIT20 (7%); SIT53 (6%), presentando una distribución similar en otras partes de Venezuela, con la diferencia de que el SIT42 y el SIT20 fueron comunes en el municipio. MIRU VNTR15 mostró que seis de las siete cepas SIT17 pertenecían a un gran grupo encontrado previamente en Venezuela, mientras las cepas SIT42, estaban relacionados a un grupo concentrado en los Barrios Unión y Maca, con un patrón MIRU VNTR no visto previamente en Venezuela. Los resultados indicarían que un gran porcentaje de tuberculosis en el municipio Sucre es causada por transmisión activa de dos familias, una reflejando comunicación con el resto del país, y otra sugiriendo que es un aislado propio de algunos Barrios del municipio.


Assuntos
Humanos , Mycobacterium tuberculosis/classificação , Tuberculose/microbiologia , Técnicas de Tipagem Bacteriana , Análise por Conglomerados , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Projetos Piloto , Reação em Cadeia da Polimerase/métodos , Características de Residência , Estudos Retrospectivos , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Tuberculose/epidemiologia , População Urbana , Venezuela/epidemiologia
7.
BMC Infect Dis ; 14: 383, 2014 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-25012075

RESUMO

BACKGROUND: Interferon-gamma release assays have emerged as a more specific alternative to the tuberculin skin test (TST) for detection of tuberculosis (TB) infection, especially in Bacille Calmette-Guérin (BCG) vaccinated people. We determined the prevalence of Mycobacterium tuberculosis infection by TST and QuantiFERON®-TB Gold In-Tube (QFT-GIT) and assessed agreement between the two test methods and factors associated with positivity in either test in Warao Amerindian children in Venezuela. Furthermore, progression to active TB disease was evaluated for up to 12 months. METHODS: 163 HIV-negative childhood household contacts under 16 years of age were enrolled for TST, QFT-GIT and chest X-ray (CXR). Follow-up was performed at six and 12 months. Factors associated with TST and QFT-GIT positivity were studied using generalized estimation equations logistic regression models. RESULTS: At baseline, the proportion of TST positive children was similar to the proportion of children with a positive QFT-GIT (47% vs. 42%, p = 0.12). Overall concordance between QFT-GIT and TST was substantial (kappa 0.76, 95% CI 0.46-1.06). Previous BCG vaccination was not associated with significantly increased positivity in either test (OR 0.68, 95% CI 0.32-1.5 for TST and OR 0.51, 95% CI 0.14-1.9 for QFT-GIT). Eleven children were diagnosed with active TB at baseline. QFT-GIT had a higher sensitivity for active TB (88%, 95% CI 47-98%) than TST (55%, 95% CI 24-83%) while specificities were similar (respectively 58% and 55%). Five initially asymptomatic childhood contacts progressed to active TB disease during follow-up. CONCLUSION: Replacement of TST by the QFT-GIT for detection of M. tuberculosis infection is not recommended in this resource-constrained setting as test results showed substantial concordance and TST positivity was not affected by previous BCG vaccination. The QFT-GIT had a higher sensitivity than the TST for the detection of TB disease. However, the value of the QFT-GIT as an adjunct in diagnosing TB disease is limited by a high variability in QFT-GIT results over time.


Assuntos
Testes de Liberação de Interferon-gama/métodos , Teste Tuberculínico/métodos , Tuberculose Pulmonar/diagnóstico , Adolescente , Criança , Bem-Estar da Criança , Pré-Escolar , Busca de Comunicante , Feminino , Humanos , Lactente , Masculino , Mycobacterium tuberculosis , Grupos Populacionais/estatística & dados numéricos , Valor Preditivo dos Testes , Kit de Reagentes para Diagnóstico , Tuberculose Pulmonar/epidemiologia , Venezuela
8.
J Infect Dev Ctries ; 8(2): 176-83, 2014 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-24518627

RESUMO

INTRODUCTION: Extraordinarily high tuberculosis (TB) prevalence rates have been reported in Venezuelan Amerindians. Amerindian populations often live in geographically isolated villages where they receive little medical attention and live under precarious sanitary conditions. TB prevalence varies by ethnicity and geographic location and is generally higher in Amerindians than in non-indigenous (Creole) people. METHODOLOGY: Between January 1, 1998 and December 31, 2009, the tuberculin skin test (TST) was administered during field operations to 9,538 Amerindian and Creole people between 0 and 94 years of age living in Venezuela. In 6,979 individuals (73%), Bacille Calmette-Guérin (BCG) vaccination status, age, and ethnicity were recorded. Univariate and multivariate analyses were performed to determine the influence of previous BCG vaccination, age, and ethnicity on TST outcomes. RESULTS: Age, ethnicity, and the number of BCG vaccinations administered each had a significant influence on TST outcomes (p < 0.001). The influence of BCG vaccination on TST outcomes varied by ethnicity and was only significant in children aged between 0 and 3 years. CONCLUSIONS: The utility of TST in the diagnosis of TB infection in high TB burden settings with widespread BCG vaccination should be evaluated locally and individually as this depends on ethnicity, age, and the number of BCG vaccinations administered. In Venezuelan children 4 years of age and older, the TST remains a useful tool for the detection of TB infection, independent of BCG vaccination status.


Assuntos
Teste Tuberculínico/métodos , Tuberculose/diagnóstico , Tuberculose/etnologia , Adolescente , Vacina BCG/administração & dosagem , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Humanos , Lactente , Modelos Lineares , Modelos Logísticos , Análise Multivariada , Mycobacterium bovis/imunologia , Prevalência , Fatores Socioeconômicos , Resultado do Tratamento , Vacinação , Venezuela/epidemiologia
9.
Invest Clin ; 55(4): 332-51, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25558753

RESUMO

Sucre municipality is a large, densely populated marginal area in the eastern part of Caracas, Venezuela that consistently has more cases of tuberculosis than other municipalities in the country. To identify the neighborhoods in the municipality with the highest prevalence of tuberculosis, and determine whether the Mycobacterium tuberculosis strain distribution in this municipality is different from that previously found in the western part of Caracas and the rest of Venezuela, we collected data on all tuberculosis cases in the municipality diagnosed in 2005-6. We performed two separate molecular epidemiological studies, spoligotyping 44 strains in a first study, and spoligotyping 131 strains, followed by MIRU-VNTR 15 on 21 clustered isolates in the second. With spoligotyping, the most common patterns were Shared International Type SIT17 (21%); SIT42 (15%); SIT93 (11%); SIT20 (7%); SIT53 (6%), a distribution similar to other parts of Venezuela, except that SIT42 and SIT20 were more common. MIRU-VNTR 15 showed that six of seven SIT17 strains examined belonged to a large cluster previously found circulating in Venezuela, but all of the SIT42 strains were related to a cluster centered in the neighborhoods of Unión and Maca, with a MIRU-VNTR pattern not previously seen in Venezuela. It appears that a large percentage of the tuberculosis in the Sucre municipality is caused by the active transmission of two strain families centered within distinct neighborhoods, one reflecting communication with the rest of the country, and the other suggesting the insular, isolated nature of some sectors.


Assuntos
Mycobacterium tuberculosis/classificação , Tuberculose/microbiologia , Técnicas de Tipagem Bacteriana , Análise por Conglomerados , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Projetos Piloto , Reação em Cadeia da Polimerase/métodos , Características de Residência , Estudos Retrospectivos , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Tuberculose/epidemiologia , População Urbana , Venezuela/epidemiologia
10.
Science ; 342(6160): 866-71, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24136356

RESUMO

Genetic mutations cause primary immunodeficiencies (PIDs) that predispose to infections. Here, we describe activated PI3K-δ syndrome (APDS), a PID associated with a dominant gain-of-function mutation in which lysine replaced glutamic acid at residue 1021 (E1021K) in the p110δ protein, the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ), encoded by the PIK3CD gene. We found E1021K in 17 patients from seven unrelated families, but not among 3346 healthy subjects. APDS was characterized by recurrent respiratory infections, progressive airway damage, lymphopenia, increased circulating transitional B cells, increased immunoglobulin M, and reduced immunoglobulin G2 levels in serum and impaired vaccine responses. The E1021K mutation enhanced membrane association and kinase activity of p110δ. Patient-derived lymphocytes had increased levels of phosphatidylinositol 3,4,5-trisphosphate and phosphorylated AKT protein and were prone to activation-induced cell death. Selective p110δ inhibitors IC87114 and GS-1101 reduced the activity of the mutant enzyme in vitro, which suggested a therapeutic approach for patients with APDS.


Assuntos
Predisposição Genética para Doença , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/patologia , Fosfatidilinositol 3-Quinases/genética , Infecções Respiratórias/genética , Infecções Respiratórias/patologia , Classe I de Fosfatidilinositol 3-Quinases , Humanos , Síndromes de Imunodeficiência/imunologia , Linfócitos/imunologia , Mutação , Linhagem , Fosfatos de Fosfatidilinositol/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Infecções Respiratórias/imunologia
11.
BMC Genomics ; 14: 74, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23375113

RESUMO

BACKGROUND: Tuberculosis (TB) continues to cause a high toll of disease and death among children worldwide. The diagnosis of childhood TB is challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. Whereas scientific and clinical research efforts to develop novel diagnostic tools have focused on TB in adults, childhood TB has been relatively neglected. Blood transcriptional profiling has improved our understanding of disease pathogenesis of adult TB and may offer future leads for diagnosis and treatment. No studies applying gene expression profiling of children with TB have been published so far. RESULTS: We identified a 116-gene signature set that showed an average prediction error of 11% for TB vs. latent TB infection (LTBI) and for TB vs. LTBI vs. healthy controls (HC) in our dataset. A minimal gene set of only 9 genes showed the same prediction error of 11% for TB vs. LTBI in our dataset. Furthermore, this minimal set showed a significant discriminatory value for TB vs. LTBI for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. In order to identify a robust representative gene set that would perform well in populations of different genetic backgrounds, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to classify 78% of the TB cases correctly with no LTBI subjects wrongly classified as TB (100% specificity). CONCLUSIONS: Our data justify the further exploration of our signature set as biomarkers for potential childhood TB diagnosis. We show that, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts.


Assuntos
Perfilação da Expressão Gênica , Índios Norte-Americanos/genética , Tuberculose/etnologia , Tuberculose/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genômica , Humanos , Lactente , Masculino , Reprodutibilidade dos Testes
12.
AIDS ; 27(11): 1783-91, 2013 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-23435304

RESUMO

OBJECTIVES: We previously reported HIV-1 infection in Warao Amerindians from Venezuela. The aim of this study was to evaluate the extent and the dynamic of HIV-1 dissemination in eight Warao communities. DESIGN AND SETTING: HIV-1 infection was evaluated in 576 Warao Amerindians from the Orinoco Delta. Partial HIV-1 pol sequences were analyzed to reconstruct the spatiotemporal and demographic dynamics of the epidemic. RESULTS: HIV-1 antibodies were present in 9.55% of Warao Amerindians, ranging from 0 to 22%. A significantly higher prevalence was found in men (15.6%) compared with women (2.6%), reaching up to 35% in men from one community. All but one isolates were classified as subtype B. Warao's HIV-1 subtype-B epidemic resulted from a single viral introduction at around the early 2000s. After an initial phase of slow growth, the subtype B started to spread at a fast rate (0.8/year) following two major routes of migration within the communities. CONCLUSION: A dramatic high prevalence was documented in almost all the communities of Warao Amerindians from the Orinoco Delta tested for HIV-1 infection. This epidemic resulted from the dissemination of a single HIV-1 subtype B founder strain introduced about 10 years ago and its size is probably doubling every year, creating a situation that can be devastating for this vulnerable Amerindian group.


Assuntos
Epidemias , Infecções por HIV/epidemiologia , HIV-1/classificação , HIV-1/isolamento & purificação , Índios Sul-Americanos , Adolescente , Adulto , Criança , Análise por Conglomerados , Feminino , Genótipo , Infecções por HIV/virologia , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Dados de Sequência Molecular , Filogeografia , Prevalência , Análise de Sequência de DNA , Venezuela/epidemiologia , Adulto Jovem , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
13.
PLoS One ; 7(7): e40626, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22808212

RESUMO

BACKGROUND: The Venezuelan Amerindians were, until recently, free of human immunodeficiency virus (HIV) infection. However, in 2007, HIV-1 infection was detected for the first time in the Warao Amerindian population living in the Eastern part of Venezuela, in the delta of the Orinoco river. The aim of this study was to analyze the genetic diversity of the HIV-1 circulating in this population. METHODOLOGY/PRINCIPAL FINDINGS: The pol genomic region was sequenced for 16 HIV-1 isolates and for some of them, sequences from env, vif and nef genomic regions were obtained. All HIV-1 isolates were classified as subtype B, with exception of one that was classified as subtype C. The 15 subtype B isolates exhibited a high degree of genetic similarity and formed a highly supported monophyletic cluster in each genomic region analyzed. Evolutionary analyses of the pol genomic region indicated that the date of the most recent common ancestor of the Waraos subtype B clade dates back to the late 1990s. CONCLUSIONS/SIGNIFICANCE: At least two independent introductions of HIV-1 have occurred in the Warao Amerindians from Venezuela. The HIV-1 subtype B was successfully established and got disseminated in the community, while no evidence of local dissemination of the HIV-1 subtype C was detected in this study. These results warrant further surveys to evaluate the burden of this disease, which can be particularly devastating in this Amerindian population, with a high prevalence of tuberculosis, hepatitis B, among other infectious diseases, and with limited access to primary health care.


Assuntos
HIV-1/fisiologia , Índios Sul-Americanos , Espécies Introduzidas , Teorema de Bayes , Genes Virais/genética , Geografia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Funções Verossimilhança , Dados de Sequência Molecular , Filogenia , Características de Residência , Fatores de Tempo , Venezuela
14.
J Infect Dev Ctries ; 5(11): 781-5, 2011 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22112731

RESUMO

INTRODUCTION: Guidelines recommend storing tuberculin purified protein derivative (PPD) refrigerated. However, especially in developing countries, maintaining the product refrigerated under field conditions can be difficult, limiting its use. Here we determine the effect of prolonged exposure to high temperatures on the potency of human, bovine and avian tuberculin PPD. METHODOLOGY: Human, bovine and avian tuberculin PPD were stored for several weeks exposed to temperatures ranging from 37º to 100ºC. The potency was evaluated in vivo, in sensitized or naturally infected animals. RESULTS: Most test situations didn't affect the biological activity of the tuberculin PPDs and only very long and extreme incubations (several days at 100 °C) compromised the potency. CONCLUSIONS: Tuberculin PPD is very stable and can be stored or transported for long periods without refrigeration. 


Assuntos
Técnicas de Laboratório Clínico/normas , Tuberculina/química , Tuberculina/farmacologia , Animais , Aves , Bovinos , Estabilidade de Medicamentos , Armazenamento de Medicamentos/métodos , Cobaias , Humanos , Estabilidade Proteica , Temperatura Ambiente , Fatores de Tempo
15.
Tuberculosis (Edinb) ; 88(5): 490-4, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18514577

RESUMO

While the gold standard for molecular epidemiological studies on tuberculosis is changing towards MIRU-VNTR typing because this technique generates easily analyzed numerical results, it is less labor intensive and has a discriminative power comparable to that of IS6110-based RFLP, especially when 24 loci are analyzed; more extensive and representative validation studies are needed to confirm this. In this study we genotyped 41 Mycobacterium tuberculosis isolates, about 40% of the total case load of the study year, from the Warao people, an indigenous population who live in a geographically isolated area in Venezuela and have a high TB incidence of 450/100,000. IS6110-based RFLP analysis on these isolates indicates that 78% of the strains are in clusters, suggesting a very high transmission rate. We show that both the 15-locus MIRU-VNTR combined with spoligotyping, as well as the 24-locus MIRU-VNTR typing have sufficient discrimination power (an HGI of 0.93 and 0.95, respectively) to replace IS6110-based RFLP (HGI=0.93) and thus are useful tools to study the molecular epidemiology of tuberculosis in this high TB incidence population.


Assuntos
Índios Sul-Americanos , Repetições Minissatélites/genética , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/epidemiologia , Impressões Digitais de DNA , Genótipo , Humanos , Dados de Sequência Molecular , Tuberculose Pulmonar/etnologia , Venezuela/epidemiologia
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