Evaluation of efficacy and safety of intradermal delivery of vaccines through microneedle(s) in human beings: a protocol for a systematic review.

BACKGROUND: Microneedles are defined as micron-sized projections with an insertion length ranging from 20 to 1500 µm and an external diameter up to 300 µm. Medications administered through microneedles diffuse through the deeper layers of the skin, into the systemic circulation, with minimal stimulation of pain-sensitive nerve endings. The rich presence of dendritic cells in the dermis makes microneedle-based vaccine delivery an attractive option. This systematic review will evaluate the efficacy and safety of intradermal delivery of vaccines using microneedles, in human beings. METHODS: We will search the following databases for studies reporting the efficacy and/or safety of intradermal delivery of vaccines using microneedles: Epistemonikos and the Cochrane Library for systematic reviews and MEDLINE (through PubMed), EMBASE, Cochrane CENTRAL, LIVIVO, Web of Science, Scopus and CINAHL databases for primary studies. We will also search grey literature databases and hand search reference lists of relevant studies. We will include randomised and quasi-randomised trials in human beings (any age), using microneedles (any material, length or bore) to deliver vaccines intradermally, wherein outcomes reflecting efficacy, safety, pain responses, participant satisfaction or cost are reported. We will additionally include non-randomised observational studies for long-term safety outcomes that are not reported in trials. Eligibility for inclusion will be independently determined by two reviewers. The risk of bias of the included studies will be assessed using the Cochrane RoB2 Tool (for randomised trials) and Newcastle-Ottawa Scale (for other study designs). Data on efficacy and safety will be pooled through meta-analysis (where feasible). We will explore the heterogeneity amongst randomised trials, using the Higgins and Thompson I2 method. We will undertake sensitivity analysis to explore the impact of study quality and subgroup analysis based on the age of participants, length of microneedle and vaccine dosage. The GRADE approach will be used to estimate the confidence in the evidence. RESULTS: This is a protocol for a systematic review; hence, there are no results at this stage. DISCUSSION: The proposed systematic review will provide evidence on efficacy, safety, pain responses, participant acceptability and cost in human beings (adults and children) for vaccines administered through the intradermal route using microneedles. Since intradermal injections using microneedles are associated with less pain due to their short lengths and narrow bores, we anticipate that delivery of vaccine antigens using this method could be a safe, efficacious and less painful alternative compared with conventional injections using hypodermic needles. The evidence in this review will be useful for policymakers, vaccine manufacturers and healthcare providers to consider this approach for the vaccination of infants and children in routine immunisation programmes. Therefore, we plan to disseminate the review through a peer-reviewed journal publication and will also provide data that cannot be included in the published version to anyone upon reasonable request. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020213608.

Determining the burden of missed opportunities for vaccination among children admitted in healthcare facilities in India: a cross-sectional study.

OBJECTIVES: Children accessing healthcare systems represent a vulnerable population with risk factors for poor health outcomes, including vaccine-preventable diseases. We aimed to quantify missed vaccination opportunities among hospitalised children in India, and identify vaccination barriers perceived by caregivers and healthcare providers. DESIGN: Cross-sectional study. SETTING: Two public-sector tertiary-care hospitals in northern India, during November 2018 and March 2019. PARTICIPANTS: We tracked 263 hospitalised children aged 1-59 months through hospital discharge, to assess vaccination status, and document catch-up vaccinations given during the hospital stay. We interviewed caregivers and healthcare providers to assess their perceptions on vaccination. OUTCOMES: Proportion of hospitalised children considered under-vaccinated for their age; proportion of missed opportunities for vaccination among under-vaccinated children who were eligible for vaccination; and vaccine coverage by antigen. RESULTS: We found that 65.4% (172/263) of hospitalised children were under-vaccinated for their age when they presented to the hospital. Among under-vaccinated children, 61.0% were less than 4 months old, and 55.6% reported prior contact with a health facility for a sick visit. The proportion of under-vaccinated children in hospitals were higher compared with the general population as indicated by regional vaccination coverage data. Among under-vaccinated children who were tracked till discharge, 98.1% (158/161) remained incompletely vaccinated at discharge and were considered 'missed opportunities for vaccination'. Perceived vaccination contraindications that are not part of established contraindications included in national and international guidelines was the most common reason for healthcare providers not to vaccinate children during hospital stay. Among caregivers of under-vaccinated children, 90.1% reported being comfortable having their children vaccinated while they were sick, if recommended by the healthcare provider. CONCLUSION: This pilot study confirmed that hospitalised sick children had substantial missed vaccination opportunities. Addressing these opportunities through concerted actions involving caregivers, healthcare providers and healthcare systems can improve overall vaccination coverage.