Immune profile and responses of a novel dengue DNA vaccine encoding an EDIII-NS1 consensus design based on Indo-African sequences.

The ongoing COVID-19 pandemic highlights the need to tackle viral variants, expand the number of antigens, and assess diverse delivery systems for vaccines against emerging viruses. In the present study, a DNA vaccine candidate was generated by combining in tandem envelope protein domain III (EDIII) of dengue virus serotypes 1-4 and a dengue virus (DENV)-2 non-structural protein 1 (NS1) protein-coding region. Each domain was designed as a serotype-specific consensus coding sequence derived from different genotypes based on the whole genome sequencing of clinical isolates in India and complemented with data from Africa. This sequence was further optimized for protein expression. In silico structural analysis of the EDIII consensus sequence revealed that epitopes are structurally conserved and immunogenic. The vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. Assaying intracellular interferon (IFN)-γ staining, immunoglobulin IgG2(a/c)/IgG1 ratios, and immune gene profiling suggests a strong Th1-dominant immune response. Finally, the passive transfer of immune sera protected AG129 mice challenged with a virulent, non-mouse-adapted DENV-2 strain. Our findings collectively suggest an alternative strategy for dengue vaccine design by offering a novel vaccine candidate with a possible broad-spectrum protection and a successful clinical translation either as a stand alone or in a mix and match strategy.

Antimicrobial resistance (AMR) at the community level: An urban and rural case study from Karnataka.

CONTEXT: The emergence of antimicrobial resistance (AMR) is a major public health crisis in India and globally. While national guidelines exist, the sources of data which form the basis of these guidelines are limited to a few well-established tertiary care centres. There is inadequate literature on AMR and antibiotic mismatch from India at community level and even less literature on AMR patterns from rural India. AIMS: The aims of this study were as follows: 1) to describe the patterns of AMR at an urban tertiary care hospital and a rural 100 bedded hospital; 2) to compare and contrast the AMR patterns noted with published ICMR guidelines; 3) to examine the issue of AMR and antibiotic mismatch; and 4) to identify local factors influencing drug-bug mismatch at the local level. SETTINGS AND DESIGN: The data were obtained from two independently conceived projects (Site 1: Urban tertiary care hospital, Site 2: Rural 100-bedded hospital). METHODS AND MATERIALS: Local antibiograms were made, and the antibiotic resistance patterns were compared between the urban and rural sites and with data published in the 2017 ICMR national guideline for AMR. STATISTICAL ANALYSIS USED: Descriptive statistics including means and medians were used. RESULTS: Our data reveal: a) a significant mismatch between sensitivity patterns and antibiotics prescribed; b) The national guidelines fail to capture the local picture of AMR, highlighting the need for local data; and c) challenges with data collection/retrieval, access and accuracy of diagnostic tools, administrative issues, and lack of local expertise limit antimicrobial stewardship efforts. CONCLUSIONS: Our study finds the burden of AMR high in both rural and urban sites, reinforcing that AMR burden cannot be ignored in rural settings. It also highlights that national data obtained from tertiary care settings fail to capture the local picture, highlighting the need for local data. Mechanisms of linking rural practices, primary health centres, and small hospitals with a common microbiology laboratory and shared data platforms will facilitate antibiotic stewardship at the community level.

The community health impasse: What can family physicians learn about integration of social determinants of health from the challenges, diversity, and worldview of primary healthcare practices located in Southern India?

CONTEXT: As social position rises, health improves. Alma Ata set the stage for community-oriented primary care (COPC), and family medicine is perfectly positioned to integrate Social Determinants of Health. India presents a unique environment for innovations in family medicine. AIMS: This study aimed to (1) assess the ability of different primary care practices to address the social determinants of health (SDoH); (2) identify key obstacles and supports; and (3) provide practical insights to family physicians and other primary care providers (PCPs) for the integration of SDoH and clinical primary care. SETTINGS AND DESIGN: A diverse sample of primary healthcare practices were selected in southern India for investigation. Data collection involved observation and informal interviews. METHODS AND MATERIAL: The researchers used general observation and informal interviews to collect data. Investigators used a basic interview guide to structure conversations and formal journal entries were recorded immediately following each visit. STATISTICAL ANALYSIS USED: Thematic analysis was conducted with NVIVO software to categorize major themes. RESULTS: Seventeen primary healthcare practices were observed; eleven were formally enrolled for interviews. Four inputs and three outputs of socially oriented primary care practices were identified. The inputs include leadership style, appropriate staffing, funding structures, and patient panels. Social interventions, community contact, and treasuring community empowerment were the major outputs. CONCLUSIONS: Community health lies at the heart of strengthening primary healthcare. Establishing practices that bridge the gap between clinical primary care and SDoH initiatives need to be prioritized. This study fosters agency for family physicians and PCPs to engage with local communities and lead the path toward this integration.

Reasons for obstetric referrals from community facilities to a tertiary obstetric facility: A study from Southern Karnataka.

CONTEXT: Pregnancy-related preventable morbidity and mortality remain high in India. Safe delivery services should focus on improving neonatal and maternal outcomes while also enabling a positive childbirth experience. However, high rates of intrapartum obstetric referrals are common. OBJECTIVE: To describe the timing and the reasons for obstetric referrals to a public tertiary care hospital in Bangalore and characteristics of the referring facilities. METHODS: We interviewed 320 women who delivered at the tertiary care hospital within a one-month time frame prior to the interview and who originally planned to deliver elsewhere. RESULTS: Ninety four percent of women in the study reported that the decision to transfer to the tertiary hospital was made after the onset of labour. Referrals were made for medical as well as non-medical reasons. About a third (35%) had to take loans to cover the expenses of childbirth. CONCLUSIONS: Referrals frequently occurred after the onset of labour. Our data imply that improving obstetric referral protocols will improve the birth experience and reduce the burden on tertiary care facilities and on the women themselves.

Managing a case of acute calculous cholecystitis at home: Highlighting the role of family physicians in providing home-based care.

Laparoscopic cholecystectomy is the generally recommended management of acute calculous cholecystitis. It is important for family physicians to be taken into consideration that for some patients the surgical risk-benefit profile favors conservative management. Here, we highlight the possibility of safe, home-based, conservative management of acute calculous cholecystitis in a patient-centered and evidence-based manner by a team of family physicians with backup support of their specialist referral network. We use this case to highlight the value of family physicians providing home-based care.