METHODOLOGY/PRINCIPAL FINDINGS: We characterized human immune sera collected during two independent outbreaks in Malaysia of the Asian genotype in 2006 and the ECSA genotype in 2008-2010. Neutralizing capacity was analyzed against representative clinical isolates as well as viruses rescued from infectious clones of ECSA and Asian CHIKV. Using whole virus antigen and recombinant E1 and E2 envelope glycoproteins, we further investigated antibody binding sites, epitopes, and antibody titers. Both ECSA and Asian sera demonstrated stronger neutralizing capacity against the ECSA genotype, which corresponded to strong epitope-antibody interaction. ECSA serum targeted conformational epitope sites in the E1-E2 glycoprotein, and E1-E211K, E2-I2T, E2-H5N, E2-G118S and E2-S194G are key amino acids that enhance cross-neutralizing efficacy. As for Asian serum, the antibodies targeting E2 glycoprotein correlated with neutralizing efficacy, and I2T, H5N, G118S and S194G altered and improved the neutralization profile. Rabbit polyclonal antibody against the N-terminal linear neutralizing epitope from the ECSA sequence has reduced binding capacity and neutralization efficacy against Asian CHIKV. These findings imply that the choice of vaccine strain may impact cross-protection against different genotypes.
CONCLUSION/SIGNIFICANCE: Immune serum from humans infected with CHIKV of either ECSA or Asian genotypes showed differences in binding and neutralization characteristics. These findings have implications for the continued outbreaks of co-circulating CHIKV genotypes and effective design of vaccines and diagnostic serological assays.
METHODS: In a randomised double-blind controlled, parallel, multicountry intervention study, 767 healthy children, ages 11 to 29 months, received GUM with scGOS/lcFOS/LCPUFAs (the active group, n = 388), GUM without scGOS/lcFOS/LCPUFAs (the control group, n = 379), or cow's milk (n = 37) for 52 weeks. The primary outcome measure was the number of episodes of upper respiratory tract infections or gastrointestinal infections based on a combination of subject's illness symptoms reported by the parents during the intervention period.
RESULTS: Children in the active group compared with the control group had a decreased risk of developing at least 1 infection (299/388 [77%] vs 313/379 [83%], respectively, relative risk 0.93, 95% confidence interval [CI] 0.87-1.00; logistic regression P = 0.03). There was a trend toward a reduction (P = 0.07) in the total number of infections in the active group, which was significant when confirmed by one of the investigators (268/388 [69%] vs 293/379 [77%], respectively, relative risk 0.89, 95% CI 0.82-0.97; P = 0.004, post hoc). More infectious episodes were observed in the cow's milk group, when compared with both GUM groups (34/37 [92%] vs 612/767 [80%], respectively, relative risk 1.15, 95% CI 1.04-1.28).
CONCLUSIONS: This is the first study in children to show a reduced risk of infection following consumption of GUM supplemented with scGOS/lcFOS/n-3 LCPUFAs. The borderline statistical significance justifies a new study to confirm this finding.
METHODS: The data from a cross-sectional study retrieved from the e-Notifikasi System, a national reporting system for communicable diseases provided by the Disease Control Division, Ministry of Health Malaysia and secondary data of all the typhoid cases were obtained from the public and private hospitals and laboratories in Klang Valley. Descriptive analysis was performed to examine the sociodemographic characteristics, spatial mapping was conducted to examine trends, and the crude incidence rates of confirmed typhoid cases and percentage of reporting coverage were calculated. Significant differences between MDR and non-MDR Salmonella typhi were determined in the patient's sociodemographic characteristics, which were analyzed using χ2 test. P values fever cases were reported in Klang Valley; however, only 265 cases were confirmed by culture tests. The crude incidence rates of confirmed cases were between 0.5 to 0.7 but peaked at 1.42 per 100,000 population in 2015. Most typhoid fever cases were observed among men (55.6%), individuals aged 21 to 30 years (27.6%), Malaysians (86.3%) and individuals of Malay ethnicity (52.1%). The reporting coverage of confirmed cases was 78.9% and non-reporting coverage of unconfirmed typhoid cases was 79.5%. The predictive value positive (PVP) was 89.3, and 7.5% were detected as MDR Salmonella typhi. Statistical significance was found in gender, citizenship and ethnicity regarding MDR Salmonella typhi (p = 0.004, p = 0.008 and p = 0.034, respectively).
CONCLUSIONS: The local transmission of typhoid is still prevalent in the Klang Valley despite rapid urbanization and development in recent years. These findings are essential for policy makers to plan and implement focused and effective preventative activities to curb typhoid infection in urban areas.