RESUMEN
BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of the phagocytic cells, which results in absent or diminished levels of microbicidal reactive oxygen species. The disease occurs due to germline mutations in the genes encoding the five subunits of NADPH oxidase complex. The present study is a pilot study to understand the clinical and genetic aspects of CGD in Sri Lanka. METHODS: Clinical records of thirteen CGD patients were analysed and compared with similar studies performed in different countries and regions to identify patterns in demographics, clinical manifestations and infectious agents. Genomic DNA and cDNA were analysed in eight patients to identify mutations in CYBB and NCF1 genes, thereby to ascertain the potential X-linked and autosomal recessive (AR) CGD patients. RESULTS: The onset of symptoms in the patient cohort was very early (mean 4.6 months) compared to 20 months in India and 23.9 months in Latin America. Similarly, the age at diagnosis was lower (mean 1.6 years after birth) compared to other studies; 4.5 years in India and 6.1 years in Europe. Pulmonary manifestations were the most common (85%), followed by skin/subcutaneous infections (77%) and lymphadenopathy (62%). The death rate of local patients (38%) was higher than other countries (India 35%, Europe 20%). Majority (77%) were treated for tuberculosis at some point in life. Genetic analysis confirmed six out of eight patients as X-linked CGD cases with mutations in CYBB gene. A novel splice site mutation was identified in P-07 at position c.141+6 which resulted in the deletion of entire exon 2. Two siblings (P-05 and P-06) from consanguineous parents, were identified with AR-CGD based on the homozygous GT deletion mutation in NCF1 gene. CONCLUSIONS: The clinical presentation, manifestations and genetic subtypes in the local cohort, appear to be comparable with global trends. Mycobacterial infections should be investigated and treated with more prominence. Effective treatment options are required to control the high mortality rate.
RESUMEN
After multiple discrete introductions of influenza A(H1N1)pdm09 virus into Sri Lanka, the virus was transmitted among humans, then swine. The spread of virus between geographically distant swine farms is consistent with virus dispersal associated with a vehicle used for swine transportation, although this remains unproven.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Infecciones por Orthomyxoviridae/veterinaria , Enfermedades de los Porcinos/epidemiología , Animales , Humanos , Gripe Humana/virología , Datos de Secuencia Molecular , Infecciones por Orthomyxoviridae/epidemiología , Infecciones por Orthomyxoviridae/virología , Filogenia , Filogeografía , ARN Viral , Sri Lanka/epidemiología , Porcinos , Enfermedades de los Porcinos/virologíaAsunto(s)
Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Orthomyxoviridae/clasificación , Orthomyxoviridae/inmunología , Formación de Anticuerpos , Antígenos Virales/inmunología , Congresos como Asunto , Industria Farmacéutica/legislación & jurisprudencia , Industria Farmacéutica/normas , Monitoreo Epidemiológico , Pruebas de Inhibición de Hemaglutinación , Humanos , Programas de Inmunización , Gripe Humana/epidemiología , Cooperación Internacional , Pruebas de Neutralización , Orthomyxoviridae/aislamiento & purificación , Suiza , Organización Mundial de la SaludRESUMEN
To study influenza viruses in pigs in Sri Lanka, we examined samples from pigs at slaughterhouses. Influenza (H3N2) and A(H1N1)pdm09 viruses were prevalent during 2004-2005 and 2009-2012, respectively. Genetic and epidemiologic analyses of human and swine influenza viruses indicated 2 events of A(H1N1)pdm09 virus spillover from humans to pigs.
Asunto(s)
Infecciones por Orthomyxoviridae/veterinaria , Infecciones del Sistema Respiratorio/veterinaria , Enfermedades de los Porcinos/virología , Mataderos , Animales , Línea Celular , Embrión de Pollo , Perros , Humanos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Infecciones por Orthomyxoviridae/epidemiología , Infecciones por Orthomyxoviridae/virología , Filogenia , Prevalencia , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Estudios Seroepidemiológicos , Sri Lanka/epidemiología , Sus scrofa/virología , Porcinos/virología , Enfermedades de los Porcinos/epidemiologíaRESUMEN
Despite greater than 99% of influenza A viruses circulating in the Asia-Pacific region being resistant to the adamantane antiviral drugs in 2011, the large majority of influenza A (>97%) and B strains (â¼99%) remained susceptible to the neuraminidase inhibitors oseltamivir and zanamivir. However, compared to the first year of the 2009 pandemic, cases of oseltamivir-resistant A(H1N1)pdm09 viruses with the H275Y neuraminidase mutation increased in 2011, primarily due to an outbreak of oseltamivir-resistant viruses that occurred in Newcastle, as reported in Hurt et al. (2011c, 2012a), where the majority of the resistant viruses were from community patients not being treated with oseltamivir. A small number of influenza B viruses with reduced oseltamivir or zanamivir susceptibility were also detected. The increased detection of neuraminidase inhibitor resistant strains circulating in the community and the detection of novel variants with reduced susceptibility are reminders that monitoring of influenza viruses is important to ensure that antiviral treatment guidelines remain appropriate.
