Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children.

Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered 'elite influenza controllers'.

Reverse genetics based H5N2 vaccine provides clinical protection against H5N1, H5N8 and H9N2 avian influenza infection in chickens.

The current study aimed to develop broadly protective vaccines for avian influenza. In an earlier study, HA stalk (universal flu vaccine) was found to be broadly protective against different subtypes of influenza virus in mice. Hence, we were interested to know its breadth of protective efficacy either alone or combined with inactivated rgH5N2 (clade 2.3.2.1a) vaccine against challenge viruses of homologous H5N1, heterologous H5N8 (clade 2.3.4.4) and heterosubtypic H9N2 virus in specific pathogen-free chickens. The rgH5N2 vaccine alone or in combination with HA stalk elicited sufficient pre-challenge immunity in the form of haemagglutination inhibiting (HI) antibodies and neutralizing antibodies (MNT) against H5N1, H5N8, and H9N2 in chickens. The rgH5N2 vaccine alone or in combination with HA stalk also attenuated the shedding of H5N1, H5N8 and H9N2 in chickens and protected against the lethal challenge of H5N1 or H5N8. In contrast, all HA stalk immunised chickens died upon H5N1 or H5N8 challenge and H9N2 challenged chickens survived. Our study suggests that the rgH5N2 vaccine can provide clinical protection against H5N1, H5N8 and can attenuate the viral shedding of H9N2 in chickens.

Outcome Predictors in Scrub Typhus Requiring Ventilator and Vasopressor Support.

BACKGROUND: Age and serum creatinine are known to be predictors of mortality in scrub typhus patients admitted in intensive care unit. This study aimed to explore the factors predicting mortality in patients with scrub typhus requiring both ventilator and vasopressor support in our set up. METHODS: A retrospective analysis of 43 patients with scrub typhus (ELISA IgM positive, optical density ?0.5) admitted in Medical Intensive Care unit of Chitwan Medical College Teaching Hospital between April 2016 to September 2017 was performed considering recovery or death (poor outcome) as outcome measurement. Potential variables (p<0.25) from bivariate analysis were used to perform a multivariate logistic regression analysis (p<0.10) to predict mortality. RESULTS: The mortality rate was 56% (24/43). Acute respiratory distress syndrome and shock were observed in all 43 patients. The median (IQR) duration of ventilation use and vasopressor use was 53(101) hours and 48(79.5) hours, respectively. On bivariate analysis, an independent and statistically significant association of mortality with age in years (p=0.039), number of vasopressor use (p<0.001) and serum creatinine more than 1.4 mg/dl (p=0.012) was observed and on multivariate regression analysis, these variables were also the predictors of mortality (age in years: p=0.011, ?=0.115, OR=1.211, 95% CI=1.027-1.225; number of vasopressor use: p=0.009, ?=3.705, OR=40.647, 95% CI=2.532-652.425; serum creatinine more than 1.4 mg/dl: p=0.046, ?=-2.205, OR=0.110, 95% CI=0.013-0.961) Conclusions: In scrub typhus with ARDS and septic shock, increasing age and serum creatinine, and requiring more than one vasopressor to maintain blood pressure are at increased risk of mortality.

Identifying the factors associated with depressive symptoms among postpartum mothers in Kathmandu, Nepal.

PURPOSE: This study aimed to identify the factors associated with depressive symptoms among postpartum mothers in Kathmandu, Nepal. METHOD: A hospital-based cross-sectional study that included 346 postpartum mothers at 4-14 weeks after delivery was carried out. Validated Nepalese version of Edinburgh Postnatal Depression Scale with cut-off value of ≥12 was used to screen depressive symptoms and structured questionnaires were used to identify the associated factors. Possible factors associated with depressive symptoms were identified by logistic regression analysis. RESULT: The mean age of the mothers was 22.75 (SD = 4.51). The prevalence of depressive symptoms among postpartum mothers was 17.1% (95% CI = 15.07-19.12). No significant association existed between postpartum depressive symptoms and socio demographic and economic characteristics. In multivariate analysis, risk factors for postpartum depressive symptoms were identified as follows: women without adequate rest during pregnancy (aOR = 4.023, 95% CI = 1.294-12.501), abortion history (aOR = 3.25, 95% CI = 1.208-9.065), poor relationship with husband (aOR = 1.67, 95% CI = 1.073-8.384), marital dissatisfaction (aOR = 4.053, 95% CI = 2.281-12.819) and stressful life events (aOR = 3.89, 95% CI = 1.504-9.810). CONCLUSIONS: This study aids to draw attention on the incorporation of routine screening for basic support and intervention for identified risk factors in postpartum period. Policies can be formulated to encourage postpartum women to obtain adequate rest during pregnancy, support women with poor partner relationship, reduce marital dissatisfaction, help women adjust with stressful life events, and prevent and manage abortion appropriately. These policies may reduce harmful consequences of postpartum depressive symptoms for women, newborn and their family.

Biofilm and metallo beta-lactamase production among the strains of Pseudomonas aeruginosa and Acinetobacter spp. at a Tertiary Care Hospital in Kathmandu, Nepal.

INTRODUCTION: Pseudomonas aeruginosa and Acinetobacter spp. are found to be associated with biofilm and metallo-ß-lactamase production and are the common causes of serious infections mainly in hospitalized patients. So, the main aims of this study were to determine the rates of biofilm production and metallo beta-lactamase production (MBL) among the strains of Pseudomonas aeruginosa and Acinetobacter spp. isolated from hospitalized patients. METHODS: A total of 85 P. aeruginosa isolates and 50 Acinetobacter spp. isolates isolated from different clinical specimens from patients admitted to Shree Birendra Hospital, Kathmandu, Nepal from July 2013 to May 2014 were included in this study. The bacterial isolates were identified with the help of biochemical tests. Modified Kirby-Bauer disc diffusion technique was used for antimicrobial susceptibility testing. Combined disc diffusion technique was used for the detection of MBL production, while Congo red agar method and tube adherence method were used for detection of biofilm production. RESULTS: Around 16.4% of P. aeruginosa isolates and 22% of the strains of Acinetobacter spp. were metallo ß-lactamase producers. Out of 85 P. aeruginosa isolates, 23 (27.05%) were biofilm producers according to tube adherence test while, only 13 (15.29%) were biofilm producers as per Congo red agar method. Similarly, out of 50 Acinetobacter spp. 7 (14%) isolates were biofilm producers on the basis of tube adherence test, while only 5 (10%) were positive for biofilm production by Congo red agar method. Highest rates of susceptibility of P. aeruginosa as well as Acinetobacter spp. were seen toward colistin. CONCLUSION: In our study, biofilm production and metallo beta-lactamase production were observed among Pseudomonas aeruginosa and Acinetobacter spp. However, no statistically significant association could be established between biofilm production and metallo beta-lactamase production.

Validating the Edinburgh Postnatal Depression Scale as a screening tool for postpartum depression in Kathmandu, Nepal.

BACKGROUND: Edinburgh Postnatal Depression Scale (EPDS) is considered well accepted screening tool for postpartum depression (PPD). The objective of the study was to validate the EPDS as a screening tool for postpartum depression in Kathmandu, Nepal. METHODS: A hospital based cross sectional study using EPDS was conducted among 346 mothers between 4 and 14 weeks of postpartum period. All the participants were examined by psychiatrist for possible clinical PPD diagnosis using International Classification of Disease tenth revision (ICD-10). Sensitivity, specificity, positive predictive value and negative predictive value were calculated for validation of EPDS. The best cut off point for Nepalese version of EPDS was identified and area of the receiver operating characteristics curve was calculated. RESULTS: The overall prevalence of PPD was 17.1 %.The sensitivity, specificity, positive predictive value and negative predictive value of the Nepalese version EPDS was found to be 92, 95.6, 77 and 99.3 % respectively. The best cut-off point of EPDS for screening of PPD was found to be 12/13 and the area of the curve was 0.98 (95 % CI 0.970-0.994, p = 0.001). CONCLUSIONS: The prevalence of PPD is not that far from the previous studies of Nepal. Nepali version of EPDS was acceptable and the study demonstrates good validity, thus EPDS can be used as valid screening tool for PPD for early detection, prompt treatment and to prevent possible consequences.