ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Influenza A Virus, H1N1 Subtype/classification , Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human/epidemiology , Orthomyxoviridae Infections/veterinary , Swine Diseases/epidemiology , Animals , Humans , Influenza, Human/virology , Molecular Sequence Data , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/virology , Phylogeny , Phylogeography , RNA, Viral , Sri Lanka/epidemiology , Swine , Swine Diseases/virologySubject(s)
Influenza Vaccines/immunology , Influenza, Human/prevention & control , Orthomyxoviridae/classification , Orthomyxoviridae/immunology , Antibody Formation , Antigens, Viral/immunology , Congresses as Topic , Drug Industry/legislation & jurisprudence , Drug Industry/standards , Epidemiological Monitoring , Hemagglutination Inhibition Tests , Humans , Immunization Programs , Influenza, Human/epidemiology , International Cooperation , Neutralization Tests , Orthomyxoviridae/isolation & purification , Switzerland , World Health OrganizationABSTRACT
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.
Subject(s)
Orthomyxoviridae Infections/veterinary , Respiratory Tract Infections/veterinary , Swine Diseases/virology , Abattoirs , Animals , Cell Line , Chick Embryo , Dogs , Humans , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza A Virus, H3N2 Subtype/isolation & purification , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/virology , Phylogeny , Prevalence , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Seroepidemiologic Studies , Sri Lanka/epidemiology , Sus scrofa/virology , Swine/virology , Swine Diseases/epidemiologyABSTRACT
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.
