ObjectiveTo determine whether inflammatory and hemostasis response in patients hospitalized for pneumonia varies by age and whether these differences explain higher mortality in the elderly.MethodsIn an observational cohort of subjects with community-acquired pneumonia (CAP) recruited from emergency departments (ED) in 28 hospitals, we divided subjects into 5 age groups (<50, 51–64, 65–74, 75–84, and ≥85). We measured circulating levels of inflammatory (TNF, IL-6, and IL-10), hemostasis (D-dimer, Factor IX, thrombin-antithrombin complex, antithrombin and plasminogen-activator inhibitor-1), and cell-surface markers (TLR-2, TLR-4, and HLA-DR) during the first week of hospitalization and at discharge and compared 90-day mortality. We used logistic regression to compare odds ratios (OR) for 90-day mortality between age groups, adjusting for differences in pre-infection factors alone and then additionally adjusting for immune markers.ResultsOf 2,183 subjects, 495, 444, 403, 583, and 258 subjects were <50, 51–64, 65–74, 75–84, and ≥85 years of age, respectively. Large age-related differences were observed in 90-day mortality (0.82% vs. 3.2% vs. 6.4% vs. 12.8% vs. 13.6%, p<0.01). No age-related differences in inflammatory and cell surface markers occurred during the first week. Older subjects had higher pro-coagulant markers on ED presentation and over first week (p≤0.03), but these differences were modest (1.0–1.7-fold differences). Odds of death for older adults changed minimally in models incorporating differences in hemostasis and inflammatory markers (for subjects ≥85 compared to those <50, OR = 4.36, when adjusted for pre-infection factors and OR = 3.49 when additionally adjusted for hemostasis markers). At discharge, despite clinical recovery as evidenced by normal vital signs in >85% subjects, older subjects had modestly increased hemostasis markers and IL-6 levels (p<0.01).ConclusionsModest age-related increases in coagulation response occur during hospitalization for CAP; however these differences do not explain the large differences in mortality. Despite clinical recovery, immune resolution may be delayed in older adults at discharge.

Although the palliative care workers at HAU have views on spirituality and spiritual care that have much in common with the palliative care literature from North America and Europe, they also face more specific challenges. These include providing spiritual care in a resource-poor setting to patients undergoing severe economic hardship, and providing spiritual care to those with traditional African religious beliefs.

Background A tetravalent live attenuated dengue vaccine, Dengvaxia, sensitised naïve recipients to severe dengue illness upon a subsequent natural dengue infection and is suspected to be due to antibody-dependent enhancement (ADE). ADE has also been implicated in the severe neurological outcomes of Zika virus (ZIKV) infection. It has become evident that cross-reactive antibodies targeting the viral pre-membrane protein and fusion-loop epitope are ADE-competent. A pre-clinical tetravalent dengue sub-unit vaccine candidate, DSV4, eliminates these ADE-competent epitopes. Methods We compared protective efficacy and ADE-competence of murine polyclonal antibodies induced by DSV4, Dengvaxia and an ‘in house’ tetravalent mixture of all four laboratory DENV strains, TV DENV, using established mouse models. Findings DSV4-induced antibodies, known to be predominantly type-specific, provided significant protection against lethal DENV challenge, but did not promote ADE of either DENV or ZIKV infection in vivo . Antibodies elicited by Dengvaxia and TV DENV, which are predominantly cross-reactive, not only failed to offer protection against lethal DENV challenge, but also promoted ADE of both DENV and ZIKV infection in vivo . Interpretation Protective efficacy against DENV infection may be linked to the induction of neutralising antibodies which are type-specific rather than cross-reactive. Whole virus-based dengue vaccines may be associated with ADE risk, despite their potent virus-neutralising capacity. Vaccines designed to eliminate ADE-competent epitopes may help eliminate/minimise ADE risk. Funding This study was supported partly by ICGEB, India, the National Biopharma Mission, DBT, Government of India, Sun Pharmaceutical Industries Limited, India, and NIAID, NIH, USA.

To develop a safe and efficacious heat-stable rotavirus vaccine, new lyophilized formulations were developed using rotavirus serotypes constituting RotaTeq®. A series of formulation compositions, differing in buffering agents, bulking agents, cryoprotectants, amino acids and divalent cations, were screened for their ability to provide stability to rotavirus serotypes during lyophilization and when stored under elevated temperatures for extended periods. Lead formulations and lyophilization cycles were further optimized. Stability profiles of thus optimized formulations showed their ability to retain the potency of rotavirus for > 36 months at 5°C, 20 months at 37°C, and 7 months at 45°C. The heat-stable lyophilized rotavirus formulations developed met the all critical quality attributes for appearance, heat-stability during storage, moisture content as well as pH, viability and stability after reconstitution and has great potential to be used as vaccine candidates for improving access in low-income countries.