Technologies for strengthening immunization coverage in India: a systematic review.

Background: Immunization coverage varies across India in different settings, geographic areas and populations. Technologies for improving immunization access can reduce disparities in coverage. This systematic review, which follows PRISMA guidelines, aims to examine the technologies for strengthening immunization coverage in India. Methods: Studies published between January 1, 2011 and July 31, 2021 were searched in Medline (through PubMed), Cochrane Library and Google Scholar. All observational and experimental studies, except qualitative studies, were included. Studies published in the English language and related to technologies for strengthening immunization, conducted on children, pregnant women, adults, elderly, healthcare personnel, caregivers and vulnerable populations across all Indian settings were included. Non-English articles, protocols, commentaries, letters, abstracts, correspondence, opinion articles, modelling, narrative and systematic reviews were excluded. Two reviewers screened studies independently, extracted data in a standardized sheet and appraised the study quality using the Mixed Methods Appraisal Tool. The primary outcome was technologies that improved immunization coverage. The protocol is registered with OSF (https://osf.io/r42gm). Findings: 6592 titles and abstracts were screened, and data extracted from 23 India-specific studies. Quality of 22/23 studies was average or above. Technologies identified included reminder systems, capacity building, community engagement and wearable technologies. Automated incentivised mobile phone reminders, immunization due-list, computerized data tracking, community mobilization and campaigns improved vaccine coverage, although effectiveness of some varied viz., reminder systems, and across states. Newer technologies included the Jyotigram Yojana, Digital Near-field Communication Pendants, "Reaching Every District" Programme and the "My Village My Home" tool. Interpretation: Technologies for improving immunization systems, capacity building and community engagement were effective. Newer technologies on vaccine delivery, mapping and cold chain logistics were not evaluated in India or were ineffective. There were limited studies in populations other than children and pregnant women. Future work is needed to evaluate the effectiveness of identified technologies across diverse settings. Funding: No funding was received for preparing this manuscript.

Building the evidence for hepatitis B vaccination programs for students and researchers working with biological samples in Indian Institutes of Higher Education.

BACKGROUND: Individuals working with biological samples in Indian universities are at risk for occupational exposure to hepatitis B virus (HBV) and may not be vaccinated. AIM: We documented the need for HBV vaccination in students and others, developed an institutional HBV vaccination program, delivered HBV vaccines, and then assessed the determinants of vaccine uptake. METHODS: Over a year, we conducted a prospective cohort study documenting the need for HBV vaccination in people working with biological materials in a major Indian institution, developed a HBV vaccination program, delivered HBV vaccines, and assessed determinants of vaccine uptake. In August 2018, a needs assessment determined exposure to blood, body fluids, and other potentially infectious material in the research setting, followed in September by a cross-sectional survey on HBV vaccination status. Institutional approval for vaccination followed in October, and vaccine clinics began in February 2019. In September, a follow-up survey investigated determinants of vaccine uptake. RESULTS: A total of 185 people participated in the baseline HBV vaccination status survey. Only 26% of students, staff, and faculty were fully vaccinated for HBV. Over 70% of the target group came forward for vaccination and >90% completed all doses. Getting vaccinated with peers strongly influenced vaccine uptake, as did availability of free vaccine, onsite clinics, and reminders. CONCLUSION: HBV vaccination programs for individuals at occupational risk are needed in Indian academic institutions beyond medical schools as part of institutional biosafety programs.

Association of nasopharyngeal viruses and pathogenic bacteria in children and their parents with and without HIV.

BACKGROUND: Bacteria and respiratory viruses co-occur in the nasopharynx, and their interactions may impact pathogenesis of invasive disease. Associations of viruses and bacteria in the nasopharynx may be affected by HIV. METHODS: We conducted a nested case-control study from a larger cohort study of banked nasopharyngeal swabs from families with and without HIV in West Bengal India, to look at the association of viruses and bacteria in the nasopharynx of parents and children when they are asymptomatic. Quantitative polymerase chain reaction for 4 bacteria and 21 respiratory viruses was run on 92 random nasopharyngeal swabs from children--49 from children living with HIV (CLH) and 43 from HIV uninfected children (HUC)-- and 77 swabs from their parents (44 parents of CLH and 33 parents of HUC). RESULTS: Bacteria was found in 67% of children, viruses in 45%, and both in 27% of child samples. Staphylococcus aureus (53%) was the most common bacteria, followed by Streptococcus pneumoniae (pneumococcus) (37%) in children and parents (53, 20%). Regardless of HIV status, viruses were detected in higher numbers (44%) in children than their parents (30%) (p = 0.049), particularly rhinovirus (p = 0.02). Human rhinovirus was the most frequently found virus in both CLH and HUC. Children with adenovirus were at six times increased risk of also having pneumococcus (Odds ratio OR 6, 95% CI 1.12-31.9) regardless of HIV status. In addition, the presence of rhinovirus in children was associated with increased pneumococcal density (Regression coeff 4.5, 1.14-7.9). In CLH the presence of rhinovirus increased the risk of pneumococcal colonization by nearly sixteen times (OR 15.6, 1.66-146.4), and, pneumococcus and S. aureus dual colonization by nearly nine times (OR 8.7). CONCLUSIONS: Children more frequently carried viruses regardless of HIV status. In CLH the presence of rhinovirus, the most frequently detected virus, significantly increased co-colonization with pneumococcus and S. aureus.

Determinants of vaccine uptake in HIV-affected families from West Bengal.

Children living with Human Immunodeficiency virus (HIV; CLH) have special vaccine needs. Determinants of household-level uptake of vaccines need to be examined in high-risk families with CLH. We previously conducted a study on the impact of Haemophilus influenzae type b conjugate vaccine and pneumococcal conjugate vaccine (PCV-13) in 125 HIV-affected families and 47 HIV-unaffected families in West Bengal. We then interviewed 99 of these 172 families who had participated in the study to understand the household-level factors that determine vaccine uptake. Sixty-four of the 99 families had one or more CLH. Within these 64 families, 30% of CLH had missed vaccines under the universal immunization program (UIP), compared to only 6% of HIV-uninfected children (HUC) (p = .001). Maternal HIV positivity in a family increased risk of missing UIP vaccines nearly five times (4.82, p = .001). Almost all families accessed UIP vaccines at local primary vaccination centers, but 14% of families experienced stigma due to HIV and avoided getting one or more vaccine doses. In contrast, in our study, 100% of HIV-affected families actively sought PCV-13 and HibCV, despite having to travel. Factors that influenced uptake included awareness generation and activation by an outreach worker and availability of vaccines on pick-up days for anti-retroviral therapy. Eighty-six percent of families strongly recommended PCV-13 to other families. To conclude, while we found that CLH have barriers to getting vaccinations, a program designed to take into consideration the obstacles that HIV-affected families face showed a high rate of vaccine uptake.

Proteomics in idiopathic pulmonary fibrosis: the quest for biomarkers.

Idiopathic pulmonary fibrosis (IPF) is a debilitating chronic progressive and fibrosing lung disease that culminates in the destruction of alveolar integrity and dismal prognosis. Its etiology is unknown and pathophysiology remains unclear. While great advances have been made in elucidating the pathogenesis mechanism, considerable gaps related to information on pathogenetic pathways and key protein targets involved in the clinical course of the disease exist. These issues need to be addressed for better clinical management of this highly challenging disease. Omics approach has revolutionized the entire area of disease understanding and holds promise in its translation to clinical biomarker discovery. This review outlines the contribution of proteomics towards identification of important biomarkers in IPF in terms of their clinical utility, i.e. prognosis, differential diagnosis, disease progression and treatment monitoring. The major dysregulated pathways associated with IPF are also discussed. Based on numerous proteomics studies on human and animal models, it is proposed that IPF pathogenesis involves complex interactions of several pathways such as oxidative stress, endoplasmic reticulum stress, unfolded protein response, coagulation system, inflammation, abnormal wounding, fibroblast proliferation, fibrogenesis and deposition of extracellular matrix. These pathways and their key path-changing mediators need further validation in large well-planned multi-centric trials at various geographical locations for successful development of clinical biomarkers of this confounding disease.

Impact of pneumococcal conjugate vaccine on the carriage density of Streptococcus pneumoniae and Staphylococcus aureus in children living with HIV: a nested case-control study.

Nasopharyngeal colonization density of Streptococcus pneumoniae (pneumococcus) is associated with disease severity and transmission. Little is known about the density of pneumococcal carriage in children with HIV (CLH). Pneumococcal vaccines may impact the density of pneumococcus and competing microbes within the nasopharynx. We examined the impact of one dose of PCV13 on carriage density of pneumococcus and Staphylococcus aureus, in CLH, HIV-uninfected children (HUC), and their unvaccinated parents. We conducted a pilot-nested case-control study, within a larger prospective cohort study, on the impact of PCV13, in families in West Bengal India. Quantitative real-time PCR was run on 147 nasopharyngeal swabs from 27 CLH and 23 HUC, and their parents, before and after PCV13 immunization. CLH had higher median pneumococcal carriage density, compared to HUC: 6.28 × 108 copies/mL vs. 2.11 × 105 copies/mL (p = .005). Following one dose of PCV13, pneumococcal densities dropped in both groups, with an increase in S. aureus carriage to 80% from 48% in CLH, and to 60% in HUC from 25%. While limited in sample size, this pilot study shows that CLH carried higher densities of pneumococcus. PCV13 was associated with a decrease in pneumococcal density and a temporal increase in S. aureus carriage regardless of HIV status.

Streptococcus pneumoniae Acquisition and Carriage in Vaccine Naïve Indian Children with HIV and their Parents: A Longitudinal Household Study.

OBJECTIVES: To investigate the difference in pneumococcal carriage, acquisition, antibiotic resistance profiles and serotype distribution, in human immunodeficiency virus (HIV) affected and unaffected families. METHODS: A prospective cohort study was conducted in children with and without HIV in West Bengal from March 2012 through August 2014, prior to 13-valent pneumococcal conjugate vaccine (PCV-13) immunization. One thousand four hundred forty one nasopharyngeal swabs were collected and cultured at five-time points from children and their parents for pneumococcal culture, and serotyping by Quellung method. RESULTS: One hundred twenty five HIV infected children and their parents, and 47 HIV uninfected children and their parents participated. Two hundred forty pneumococcal isolates were found. In children under 6 y, the point prevalence of colonization was 31% in children living with HIV (CLH) and 32% in HIV uninfected children (HUC), p = 0.6. The most common vaccine type (VT) serotypes were 6A, 6B and 19A. All isolates from parents and 71% from children in the HIV uninfected cohort were PCV-13 representative, compared to 33% of isolates from CLH and their parents. Acquisition rate in children was 1.77 times that of parents (OR = 1.77, 95%CI: 1.18-2.65). The HIV status of child or parent did not affect acquisition. Isolates from CLH were more frequently resistant to multiple antibiotics (p = 0.02). CONCLUSIONS: While the rate of pneumococcal carriage and acquisition did not differ between CLH and HUC, HIV affected families had exposure to a wider range of serotypes including non-vaccine type serotypes and antibiotic resistant serotypes, than HIV unaffected families.

Increased household exposure to respiratory pathogens in HIV exposed uninfected children due to maternal HIV.

Little is known about household exposures to respiratory pathogens in HIV-exposed uninfected children (HEU) in Indian families. This case series investigates the nasopharyngeal carriage of Streptococcus pneumoniae, Staphylococcus aureus, and respiratory viruses at multiple points in three mother child pairs: (1) an HIV-infected child and mother, (2) an HEU child and HIV-infected mother, and (3) an HIV-unexposed uninfected (HUU) child and mother. Nasopharyngeal carriage densities of Streptococcus pneumoniae and Staphylococcus aureus were higher in mothers and children living in HIV-affected households, regardless of the child's HIV status. Maternal HIV and ART status impact these household exposures.

New insights into therapeutic activity and anticancer properties of curcumin.

Natural compounds obtained from plants are capable of garnering considerable attention from the scientific community, primarily due to their ability to check and prevent the onset and progress of cancer. These natural compounds are primarily used due to their nontoxic nature and the fewer side effects they cause compared to chemotherapeutic drugs. Furthermore, such natural products perform even better when given as an adjuvant along with traditional chemotherapeutic drugs, thereby enhancing the potential of chemotherapeutics and simultaneously reducing their undesired side effects. Curcumin, a naturally occurring polyphenol compound found in the plant Curcuma longa, is used as an Indian spice. It regulates not only the various pathways of the immune system, cell cycle checkpoints, apoptosis, and antioxidant response but also numerous intracellular targets, including pathways and protein molecules controlling tumor progression. Many recent studies conducted by major research groups around the globe suggest the use of curcumin as a chemopreventive adjuvant molecule to maximize and minimize the desired effects and side effects of chemotherapeutic drugs. However, low bioavailability of a curcumin molecule is the primary challenge encountered in adjuvant therapy. This review explores different therapeutic interactions of curcumin along with its targeted pathways and molecules that are involved in the regulation of onset and progression of different types of cancers, cancer treatment, and the strategies to overcome bioavailability issues and new targets of curcumin in the ever-growing field of cancer.

Serum metabolomics of Indian women with polycystic ovary syndrome using 1H NMR coupled with a pattern recognition approach.

Polycystic ovary syndrome (PCOS) is one of the most commonly occurring metabolic and endocrinological disorders affecting women of reproductive age. Metabolomics is an emerging field that holds promise in understanding disease pathophysiology. Recently, a few metabolomics based studies have been attempted in PCOS patients; however, none of them have included patients from the Indian population. The main objective of this study was to investigate the serum metabolomic profile of Indian women with PCOS and compare them with controls. Proton nuclear magnetic resonance (1H NMR) was used to first identify the differentially expressed metabolites among women with PCOS from the Eastern region of India during the discovery phase and further validated in a separate cohort of PCOS and control subjects. Multivariate analysis of the binned spectra indicated 16 dysregulated bins in the sera of these women with PCOS. Out of these 16 bins, 13 identified bins corresponded to 12 metabolites including 8 amino acids and 4 energy metabolites. Amongst the amino acids, alanine, valine, leucine and threonine and amongst the energy metabolites, lactate and acetate were observed to be significantly up-regulated in women with PCOS when compared with controls. The remaining 4 amino acids, l-glutamine, proline, glutamate and histidine were down-regulated along with 2 energy metabolites: glucose and 3-hydroxybutyric acid. Our findings showed dysregulations in the expression of different metabolites in the serum of women with PCOS suggesting the involvement of multiple pathways including amino acid metabolism, carbohydrate/lipid metabolism, purine and pyrimidine metabolism and protein synthesis.

Membrane-bound IL-12 and IL-23 serve as potent mucosal adjuvants when co-presented on whole inactivated influenza vaccines.

BACKGROUND: Potent and safe adjuvants are needed to improve the efficacy of parenteral and mucosal vaccines. Cytokines, chemokines and growth factors have all proven to be effective immunomodulatory adjuvants when administered with a variety of antigens. We have previously evaluated the efficacy of membrane-anchored interleukins (IL) such as IL-2 and IL-4 co-presented as Cytokine-bearing Influenza Vaccines (CYT-IVACs) using a mouse model of influenza challenge. FINDINGS: Here, we describe studies evaluating the parenteral and mucosal adjuvanticity of membrane-bound IL-12 and IL-23 CYT-IVACs in young adult mice. Mucosal immunization using IL-12 and IL-23 bearing whole influenza virus vaccine (WIV) was more effective at eliciting virus-specific nasal IgA and reducing viral lung burden following challenge compared to control WIV vaccinated animals. Both IL-12 and IL-23 bearing WIV elicited the highest anti-viral IgA levels in serum and nasal washes. CONCLUSIONS: This study highlights for the first time the mucosal adjuvant potential of IL-12 and IL-23 CYT-IVAC formulations in eliciting mucosal immune responses and reducing viral lung burden. The co-presentation of immunomodulators in direct context with viral antigen in whole inactivated viral vaccines may provide a means to significantly lower the dose of vaccine required for protection.

Tailored vaccines targeting the elderly using whole inactivated influenza vaccines bearing cytokine immunomodulators.

Influenza and its complications disproportionately affect the elderly, leading to high morbidity and mortality in this ever-increasing population. Despite widespread vaccination efforts, the current influenza vaccines are less effective in the elderly; hence newer vaccine strategies are needed to improve their efficacy in this age group. We have previously shown that co-presentation of cytokines on the surface of inactivated influenza virus particles affords better protection from lethal homotypic viral challenge in young adult mice than conventional non-adjuvanted whole inactivated vaccine. Here, we determined the efficacy of these vaccine formulations in Balb/c mice "aged" to 17 months ("aged mice") along with the addition of a membrane-bound interleukin-12 (IL-12) vaccine formulation. Our investigations found that a single low-dose intramuscular vaccination with inactivated whole influenza vaccine co-presenting IL-12 was sufficient to provide enhanced protection from subsequent influenza challenge as compared with non-adjuvanted whole inactivated vaccine. Our results indicate that incorporation of cytokines such as IL-12 in a membrane-bound formulation in whole inactivated vaccine may provide a means to lower the vaccine dose while eliciting enhanced protective responses in the elderly, an age group that responds poorly to current vaccination regimens.

Reducing maternal mortality among Afghan refugees in Pakistan.

OBJECTIVE: The International Rescue Committee (IRC) strove to reduce maternal mortality among Afghan refugees in Hangu district of Pakistan by improving access to emergency obstetric care (EmOC), community knowledge of danger signs of pregnancy, and the use of health information. METHODS: IRC established EmOC centers, trained community members on safe motherhood, linked primary health care with education on danger signs of pregnancy and the importance of skilled attendance, and improved the health information system. RESULTS: The maternal mortality ratio among Afghan refugees in the area improved from 291 per 100000 live births in 2000 to 102 per 100000 live births in 2004. The proportion of refugee births attended by skilled staff increased from 5% in 1996 to 67% in 2007. Complete prenatal care coverage increased from 49% in 2000 to 90% in 2006, and postnatal coverage more than trebled from 27% in 2000 to 85% in 2006. CONCLUSION: Improved services, community involvement and education, good coordination, and effective systems succeeded in reducing maternal mortality in a traditionally conservative environment.