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1.
BMC Genomics ; 18(1): 324, 2017 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-28438140

RESUMEN

BACKGROUND: Genomic characterization of rotavirus (RoV) has not been adopted at large-scale due to the complexity of obtaining sequences for all 11 segments, particularly when feces are used as starting material. METHODS: To overcome these limitations, we developed a novel RoV capture and genome sequencing method combining commercial enzyme immunoassay plates and a set of routinely used reagents. RESULTS: Our approach had a 100% success rate, producing >90% genome coverage for diverse RoV present in fecal samples (Ct < 30). CONCLUSIONS: This method provides a novel, reproducible and comparatively simple approach for genomic RoV characterization and could be scaled-up for use in global RoV surveillance systems. TRIAL REGISTRATION (PROSPECTIVELY REGISTERED): Current Controlled Trials ISRCTN88101063 . Date of registration: 14/06/2012.


Asunto(s)
Heces/virología , Genómica/métodos , Genotipo , Virus Reordenados/genética , Rotavirus/genética , Análisis de Secuencia de ARN/métodos , ADN Complementario/genética , Genoma Viral/genética , Humanos , Filogenia , Virus Reordenados/fisiología , Rotavirus/fisiología , Carga Viral
2.
Am J Respir Cell Mol Biol ; 52(3): 342-8, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25078322

RESUMEN

CD43, a surface glycoprotein, regulates Mycobacterium tuberculosis macrophage binding, replication, and proinflammatory cytokine induction in a murine model. We hypothesized that single-nucleotide polymorphisms (SNPs) in the CD43 gene region are associated with human tuberculosis (TB) susceptibility. We performed a case-population study in discovery (352 TB cases and 382 control subjects) and validation cohorts (339 TB cases and 376 control subjects). We examined whether 11 haplotype-tagging SNPs in the CD43 gene region were associated with tuberculous meningitis (TBM) and pulmonary TB (PTB) in Vietnam. Three SNPs from the CD43 gene region were associated with TB susceptibility with a genotypic model. The association fit a recessive genetic model and was greater for TBM than for PTB (for TBM: rs4788172, odds ratio [OR], 1.64; 95% confidence interval [CI], 1.04-2.59, rs17842268 [OR, 2.20; 95% CI, 1.29-3.76, and rs12596308 [OR, 2.38; 95% CI, 1.47-3.89]). Among TBM cases, rs17842268 was associated with decreased survival (hazard ratio, 2.7; 95% CI, 1.1-6.5; P = 0.011). In addition, rs12596308 and rs17842268 were associated with focal neurologic deficit at TBM presentation. Our data suggest that CD43 polymorphisms are associated with TB susceptibility, disease manifestations, and worse outcomes. To our knowledge, this is the first report that links CD43 genetic variants with susceptibility and outcome from a disease.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Leucosialina/genética , Polimorfismo de Nucleótido Simple/genética , Tuberculosis Meníngea/genética , Tuberculosis Pulmonar/genética , Estudios de Casos y Controles , Haplotipos/genética , Humanos , Mycobacterium tuberculosis
3.
Microbiol Spectr ; 11(6): e0256223, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37971428

RESUMEN

IMPORTANCE: Drug-resistant tuberculosis (TB) infection is a growing and potent concern, and combating it will be necessary to achieve the WHO's goal of a 95% reduction in TB deaths by 2035. While prior studies have explored the evolution and spread of drug resistance, we still lack a clear understanding of the fitness costs (if any) imposed by resistance-conferring mutations and the role that Mtb genetic lineage plays in determining the likelihood of resistance evolution. This study offers insight into these questions by assessing the dynamics of resistance evolution in a high-burden Southeast Asian setting with a diverse lineage composition. It demonstrates that there are clear lineage-specific differences in the dynamics of resistance acquisition and transmission and shows that different lineages evolve resistance via characteristic mutational pathways.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Beijing , Vietnam/epidemiología , Genotipo , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Farmacorresistencia Bacteriana Múltiple/genética , Mutación
4.
Clin Infect Dis ; 51(9): e65-8, 2010 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-20887205

RESUMEN

AIDS‐associated Cryptococcus neoformans and Penicillium marneffei coinfection has not been adequately studied and poses unique therapeutic challenges in resource‐limited settings. Itraconazole poorly penetrates the central nervous system, whereas fluconazole has poor activity against P. marneffei. We prospectively report management of 1 patient and retrospectively review 7 coinfection cases from Vietnam.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Antifúngicos/farmacocinética , Antifúngicos/uso terapéutico , Cryptococcus neoformans/aislamiento & purificación , Micosis/diagnóstico , Micosis/tratamiento farmacológico , Penicillium/aislamiento & purificación , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Adulto , Cryptococcus neoformans/efectos de los fármacos , Países en Desarrollo , Diagnóstico Diferencial , Fluconazol/farmacocinética , Fluconazol/uso terapéutico , Humanos , Itraconazol/farmacocinética , Itraconazol/uso terapéutico , Masculino , Micosis/microbiología , Penicillium/efectos de los fármacos , Estudios Prospectivos , Estudios Retrospectivos , Vietnam
5.
Clin Infect Dis ; 50(5): 679-85, 2010 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-20105074

RESUMEN

BACKGROUND: World Health Organization treatment guidelines recommend that adults with severe malaria be admitted to an intensive care unit (ICU). However, ICU facilities are limited in the resource-poor settings where most malaria occurs. Identification of patients at greater risk of complications may facilitate their triage and resource allocation. METHODS: With use of data from a trial conducted in Southeast Asia (n=868), a logistic regression model was built to identify independent predictors of mortality among adults with severe malaria. A scoring system based on this model was tested in the original dataset and then validated in 2 series from Bangladesh (n=188) and Vietnam (n=292). RESULTS: Acidosis (base deficit) and cerebral malaria (measured as Glasgow Coma Score) were the main independent predictors of outcome. The 5-point Coma Acidosis Malaria (CAM) score was simply derived from these 2 variables. Mortality increased steadily with increasing score. A CAM score <2 predicted survival with a positive predictive value (PPV) of 95.8% (95% confidence interval [CI], 93%- 97.7%). Of the 14 of 331 patients who died with a CAM score <2, 11 (79%) had renal failure and death occurred late after hospital admission (median, 108 h; range, 40-360 h). Substitution of plasma bicarbonate as the measure of acidosis only slightly reduced the prognostic value of the model. Use of respiratory rate was inferior, but a score <2 still predicted survival with a PPV of 92.2% (95% CI, 89.1%-94.7%). CONCLUSIONS: Patients with a CAM score <2 at hospital admission may be safely treated in a general ward, provided that renal function can be monitored.


Asunto(s)
Malaria/diagnóstico , Malaria/patología , Índice de Severidad de la Enfermedad , Acidosis/patología , Adulto , Bangladesh , Coma/patología , Femenino , Humanos , Malaria/mortalidad , Masculino , Pronóstico , Vietnam
6.
Pediatr Infect Dis J ; 37(1): 35-42, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28787388

RESUMEN

BACKGROUND: Probiotics are the most frequently prescribed treatment for children hospitalized with diarrhea in Vietnam. We were uncertain of the benefits of probiotics for the treatment of acute watery diarrhea in Vietnamese children. METHODS: We conducted a double-blind, placebo-controlled, randomized trial of children hospitalized with acute watery diarrhea in Vietnam. Children meeting the inclusion criteria (acute watery diarrhea) were randomized to receive either 2 daily oral doses of 2 × 10 CFUs of a local probiotic containing Lactobacillus acidophilus or placebo for 5 days as an adjunct to standard of care. The primary end point was time from the first dose of study medication to the start of the first 24-hour period without diarrhea. Secondary outcomes included the total duration of diarrhea and hospitalization, daily stool frequency, treatment failure, daily fecal concentrations of rotavirus and norovirus, and Lactobacillus colonization. RESULTS: One hundred and fifty children were randomized into each study group. The median time from the first dose of study medication to the start of the first 24-hour diarrhea-free period was 43 hours (interquartile range, 15-66 hours) in the placebo group and 35 hours (interquartile range, 20-68 hours) in the probiotic group (acceleration factor 1.09 [95% confidence interval, 0.78-1.51]; P = 0.62). There was also no evidence that probiotic treatment was efficacious in any of the predefined subgroups nor significantly associated with any secondary end point. CONCLUSIONS: This was a large double-blind, placebo-controlled trial in which the probiotic underwent longitudinal quality control. We found under these conditions that L. acidophilus was not beneficial in treating children with acute watery diarrhea.


Asunto(s)
Diarrea/terapia , Lactobacillus acidophilus , Probióticos/uso terapéutico , Preescolar , Diarrea/epidemiología , Diarrea/virología , Método Doble Ciego , Femenino , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Rotavirus , Infecciones por Rotavirus , Vietnam , Carga Viral
7.
Trials ; 17(1): 279, 2016 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-27266697

RESUMEN

BACKGROUND: Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam. METHODS/DESIGN: This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events. DISCUSSION: In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015.


Asunto(s)
Albendazol/efectos adversos , Antihelmínticos/efectos adversos , Diarrea/epidemiología , Helmintiasis/prevención & control , Infecciones Oportunistas/epidemiología , Adolescente , Factores de Edad , Albendazol/administración & dosificación , Antihelmínticos/administración & dosificación , Niño , Protocolos Clínicos , Diarrea/diagnóstico , Diarrea/microbiología , Diarrea/virología , Método Doble Ciego , Esquema de Medicación , Femenino , Helmintiasis/diagnóstico , Helmintiasis/epidemiología , Helmintiasis/parasitología , Humanos , Incidencia , Masculino , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/virología , Prevalencia , Proyectos de Investigación , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Vietnam/epidemiología
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