Childhood allergic diseases across geographical regions of Kandy and Anuradhapura districts of Sri Lanka; where do the rates stand among other regions: experience from Global asthma network Phase 1 study.

BACKGROUND: Asthma, allergic rhinitis and eczema have been identified as the most prevalent childhood allergic diseases. However, the prevalence of these allergic diseases can vary in different regions within a country and in the world. METHODS: The objective of the study was to estimate the prevalence of asthma, allergic rhinitis and eczema in schoolchildren in the Kandy and Anuradhapura districts of Sri Lanka. This was a multicentre cross sectional study carried out among children of age 6-7 years and 13-14 years attending state schools fulfilling the entry criteria of the Global Asthma Network Phase 1 study methodology. RESULTS: A total of 3673 children of 6-7 years and 4658 children of 13-14 years were recruited. The prevalence of current asthma, allergic rhinitis and eczema were 12% (CI 10.44-13.75), 15.7% (CI 13.94-17.64) and 9.7% (CI 8.30-11.31) among 6-7 years age group and 15.3% (CI 13.66-17.09), 30.5% (CI 28.86-32.74) and 7.3% (CI 6.15-8.65) respectively among the 13-14 age group in Kandy district. The reported prevalence rates of the disease conditions were 9.9% (CI 8.72-11.22), 10.1% (CI 8.90-11.44) and 5.9% (CI 4.98-6.98) among 6-7 years age group and 14.9% (CI 13.67-16.22), 22.5% (CI 21.04-24.03) and 1.8% (CI 1.38-2.34) in the 13-14 years age group in Anuradhapura district. When comparing these prevalence rates, there is relatively a higher prevalence of childhood allergic diseases in Kandy district. This difference is statistically significant in all three allergic disease conditions (P < 0.001). CONCLUSION: Prevalence of allergic diseases in Anuradhapura is closer to reported data in the previous studies. There is relatively higher prevalence of childhood allergic diseases among children in Kandy district.

MERS-CoV ORF4b employs an unusual binding mechanism to target IMPα and block innate immunity.

The MERS coronavirus (MERS-CoV) is a highly pathogenic, emerging virus that produces accessory proteins to antagonize the host innate immune response. The MERS-CoV ORF4b protein has been shown to bind preferentially to the nuclear import adapter IMPα3 in infected cells, thereby inhibiting NF-κB-dependent innate immune responses. Here, we report high-resolution structures of ORF4b bound to two distinct IMPα family members. Each exhibit highly similar binding mechanisms that, in both cases, lack a prototypical Lys bound at their P2 site. Mutations within the NLS region dramatically alter the mechanism of binding, which reverts to the canonical P2 Lys binding mechanism. Mutational studies confirm that the novel binding mechanism is important for its nuclear import, IMPα interaction, and inhibition of innate immune signaling pathways. In parallel, we determined structures of the nuclear binding domain of NF-κB component p50 bound to both IMPα2 and α3, demonstrating that p50 overlaps with the ORF4b binding sites, suggesting a basis for inhibition. Our results provide a detailed structural basis that explains how a virus can target the IMPα nuclear import adapter to impair immunity, and illustrate how small mutations in ORF4b, like those found in closely related coronaviruses such as HKU5, change the IMPα binding mechanism.

Colonization with selected antibiotic resistant bacteria among a cohort of Sri Lankan university students.

BACKGROUND: Antibiotic Resistance is an imminent global public health threat. Antibiotic resistance emerged in healthcare settings and has now moved on to the community settings. This study was conducted to identify the rates of asymptomatic colonization with selected antibiotic resistant organisms, (Methicillin Resistant Staphylococcus aureus (MRSA), Extended Spectrum Beta Lactamase (ESBL) producing Escherichia coli and Klebsiella spp and carbapenem resistant E.coli and Klebsiella spp) - among a group of university students in Sri Lanka. Identification of genetic determinants of MRSA and ESBL was an additional objective of the study. METHODS: A self - collected nasal swab and a peri-rectal swab collected after passing stools were obtained. Routine microbiological methods were used for the isolation S.aureus from the nasal swab and E.coli and Klebsiella species from the peri-rectal swab. Antibiotic sensitivity testing was performed as recommended by clinical and laboratory standard institute (CLSI). Three (3) genes that are responsible for ESBL production; blaCTX-M, blaSHV, and blaTEM were tested using previously described primers and PCR procedures. Identification of MecA and PVL genes attributed to MRSA was also done with PCR. RESULTS: A total of 322 participants between 21 and 28 years were recruited representing 5 different faculties of study. Seventy one (22.0%) were colonized with S.aureus and 14 among them with MRSA, making the MRSA colonization rate of 4.3%. Forty five (15%) of the participants were colonized with an ESBL producing E.coli or Klebsiella spp. No one was colonized with carbapenem resistant E.coli or Klebsiella species. Of the 45 ESBL producers the commonest genetic determinant identified was blaCTX-M (n = 36), while 16 isolates had blaTEM and 7 had blaSHV. Similarly, of the 14 isolates identified as MRSA, 3 (21.4%) were found to be PVL positive while 11 (78.6%) were MecA positive. CONCLUSIONS: A high rate of colonization with ESBL producing E.coli and Klebsiella species was noted in our study group.

Pneumococcal colonization among healthy and hospitalized vaccine-naive Sri Lankan children.

BACKGROUND: Streptococcus pneumoniae continues to cause mortality and morbidity despite availability of effective vaccines. Pneumococcal colonization is considered a pre-requisite for disease. Identifying the serotypes circulating in a given locale is important for surveillance purposes as well as for assessing the need for vaccination. Aim of the present study was to identify nasopharyngeal pneumococcal colonization rates in healthy children and children with respiratory tract infections in central Sri Lanka. METHOD: A total of 450 nasopharyngeal swabs (NPS) of children aged between 2 months and 2 years were collected from two groups; healthy children and children hospitalized with respiratory symptoms. NPS samples were processed using conventional laboratory techniques to isolate S. pneumoniae. Antibiotic susceptibility patterns of pneumococcal isolates were identified using CLSI disc diffusion method and minimum inhibitory concentration (MIC) was determined by micro-broth dilution method. RESULTS: Pneumococcal colonization rate among healthy children was 31.8% (143/450) it was 39.8% (179/450) in children hospitalized with respiratory symptoms. MIC for penicillin and cefotaxime ranged between 0.015 to 4 µg/ml and <0.015 to 16 µg/ml respectively. All isolates were susceptible to levofloxacin, vancomycin, linezolid and rifampicin. Erythromycin and tetracycline non-susceptibility rates were >50% in both groups. The predominant serotypes identified were 19F (n = 66, 20.5%), 6B (n = 43, 13.4%), 6A (n = 30, 9.3%), 23F (n = 28, 8.7%) and 14 (n = 20, 6.2%). Among healthy children, presence of school going children at home and the number of household members were significantly associated with pneumococcal colonization while in hospitalized children, pneumococcal colonization was significantly associated with presence of school going children at home. CONCLUSION: Pneumococcal colonization rates were considerably higher in both study cohorts and the commonest serotypes were 19F, 6B, 6A, 23F and 14. Antibiotic resistance rates were also relatively higher among the pneumococcal isolates.

Community acquired paediatric pneumonia; experience from a pneumococcal vaccine- naive population.

BACKGROUND: Childhood pneumonia continues to be a disease that causes severe morbidity and mortality among children mainly in South-East Asia and Africa though it is not so in the developed world. Pneumonia accounts for 16% of all deaths of children under 5 years old in the world, killing nearly one million children in 2015. In Sri Lanka, there were 21,000 reported cases of pneumonia in 2006, 40% were in the age group of less than 4 years. METHODS: This was a retrospective study done on the children aged 1 month to 14 years who were admitted to the Professorial Paediatric unit of Teaching Hospital, Peradeniya between 1st of March 2016 and 30th of July 2017 fulfilling diagnostic criteria for community-acquired pneumonia. Data including diagnosis, clinical details, management details and other relevant data were collected from patient records by using a data collection sheet. RESULTS: In this study, 48% of 127 patients admitted with community-acquired pneumonia had bronchopneumonia. About 2/3 of the patients neededa secondline of intravenous antibiotics while 51/ 127 needed care in the high dependency unit with supplemental oxygen. No mortality was observed in the group. CONCLUSIONS: Community- acquired paediatric pneumonia has a significant associated morbidity but not mortality in the studied population. The need for the second-line treatment with intravenous antibiotics in a significant proportion of patients may indicate a high degree of antibiotic resistance. Introduction of national antibiotic policy will help the cause.