A social justice perspective on access to human rabies vaccines

Rabies kills tens of thousands of people every year despite being entirely vaccine preventable. Key global health actors have launched a country-driven plan to achieve zero human deaths from dog-mediated rabies by 2030 worldwide. This partnership has recently been strengthened by Gavi, the Vaccine Alliance’s decision to invest in human rabies vaccines for post-exposure prophylaxis (PEP). While nation states are key to rabies elimination, the importance of Gavi's role cannot be understated. Unlike any other actor, Gavi can directly address an otherwise intractable market failure in the inadequate supply of rabies PEP. In this commentary, we employ the Capabilities Approach to identify the barriers to PEP access that lead to this market failure and, as a result, unnecessary deaths and suffering. We show the role that Gavi can play in reducing exposure of PEP supply to market forces as a matter of social justice, and hence redress the inequity underlying human rabies deaths

Rabies vaccine and immunoglobulin supply and logistics: Challenges and opportunities for rabies elimination in Kenya

Prompt provision of post-exposure-prophylaxis (PEP) including vaccines and rabies immunoglobulin (RIG) to persons bitten by suspect rabid dogs is a key strategy to eliminating human deaths from dog-mediated rabies in Kenya by 2030. We assessed the availability, forecasting and supply chain logistics for rabies PEP in Kenya, compared with the system used for vaccines in the expanded program of immunization (routine vaccines). Semi-structured questionnaires capturing data on forecasting, procurement, distribution, cold chain and storage, monitoring and reporting for routine vaccines and rabies vaccines and RIG were administered to 35 key personnel at the national, county, sub-county and health facility levels in five counties. Results showed large variability in PEP availability (stockouts ranged from 3 to 36 weeks per year) with counties implementing rabies elimination activities having shorter stockouts. PEP is administered intramuscularly using the 5-dose Essen regimen (day 0, 3, 7, 14 and 28). PEP costs to bite patients were reported to range from 10 to 15 US dollars per dose; RIG was seldom available. A less robust supply and logistics infrastructure is used for rabies PEP compared to routine vaccines. Forecasting and monitoring mechanisms for rabies PEP was poor in the study counties. The supply of vaccines from the national to the sub-national level is mainly through two government agencies and a private agency. Since government decentralization, the National Vaccine and Immunization Program has remained as the main supplier of the routine vaccines, playing a lesser role in the supply of rabies biologicals. Adoption of the dose-saving intradermal route for PEP administration, reduction of PEP costs to patients, and placing rabies vaccines within the routine vaccines supply and logistics system would significantly improve PEP availability and accessibility to persons at risk of rabies; a critical step to achieving elimination of human deaths from rabies

Portable Rabies Virus Sequencing in Canine Rabies Endemic Countries Using the Oxford Nanopore MinION

As countries with endemic canine rabies progress towards elimination by 2030, it will become necessary to employ techniques to help plan, monitor, and confirm canine rabies elimination. Sequencing can provide critical information to inform control and vaccination strategies by identifying genetically distinct virus variants that may have different host reservoir species or geographic distributions. However, many rabies testing laboratories lack the resources or expertise for sequencing, especially in remote or rural areas where human rabies deaths are highest. We developed a low-cost, high throughput rabies virus sequencing method using the Oxford Nanopore MinION portable sequencer. A total of 259 sequences were generated from diverse rabies virus isolates in public health laboratories lacking rabies virus sequencing capacity in Guatemala, India, Kenya, and Vietnam. Phylogenetic analysis provided valuable insight into rabies virus diversity and distribution in these countries and identified a new rabies virus lineage in Kenya, the first published canine rabies virus sequence from Guatemala, evidence of rabies spread across an international border in Vietnam, and importation of a rabid dog into a state working to become rabies-free in India. Taken together, our evaluation highlights the MinION’s potential for low-cost, high volume sequencing of pathogens in locations with limited resources

Rapid in-country sequencing of whole virus genomes to inform rabies elimination programmes.

Genomic surveillance is an important aspect of contemporary disease management but has yet to be used routinely to monitor endemic disease transmission and control in low- and middle-income countries. Rabies is an almost invariably fatal viral disease that causes a large public health and economic burden in Asia and Africa, despite being entirely vaccine preventable. With policy efforts now directed towards achieving a global goal of zero dog-mediated human rabies deaths by 2030, establishing effective surveillance tools is critical. Genomic data can provide important and unique insights into rabies spread and persistence that can direct control efforts. However, capacity for genomic research in low- and middle-income countries is held back by limited laboratory infrastructure, cost, supply chains and other logistical challenges. Here we present and validate an end-to-end workflow to facilitate affordable whole genome sequencing for rabies surveillance utilising nanopore technology. We used this workflow in Kenya, Tanzania and the Philippines to generate rabies virus genomes in two to three days, reducing costs to approximately £60 per genome. This is over half the cost of metagenomic sequencing previously conducted for Tanzanian samples, which involved exporting samples to the UK and a three- to six-month lag time. Ongoing optimization of workflows are likely to reduce these costs further. We also present tools to support routine whole genome sequencing and interpretation for genomic surveillance. Moreover, combined with training workshops to empower scientists in-country, we show that local sequencing capacity can be readily established and sustainable, negating the common misperception that cutting-edge genomic research can only be conducted in high resource laboratories. More generally, we argue that the capacity to harness genomic data is a game-changer for endemic disease surveillance and should precipitate a new wave of researchers from low- and middle-income countries

The potential effect of improved provision of rabies post-exposure prophylaxis in Gavi-eligible countries: a modelling study

Background: Tens of thousands of people die from dog-mediated rabies annually. Deaths can be prevented through post-exposure prophylaxis for people who have been bitten, and the disease eliminated through dog vaccination. Current post-exposure prophylaxis use saves many lives, but availability remains poor in many rabies-endemic countries due to high costs, poor access, and supply. Methods: We developed epidemiological and economic models to investigate the effect of an investment in post-exposure prophylaxis by Gavi, the Vaccine Alliance. We modelled post-exposure prophylaxis use according to the status quo, with improved access using WHO-recommended intradermal vaccination, with and without rabies immunoglobulin, and with and without dog vaccination. We took the health provider perspective, including only direct costs. Findings: We predict more than 1 million deaths will occur in the 67 rabies-endemic countries considered from 2020 to 2035, under the status quo. Current post-exposure prophylaxis use prevents approximately 56 000 deaths annually. Expanded access to, and free provision of, post-exposure prophylaxis would prevent an additional 489 000 deaths between 2020 and 2035. Under this switch to efficient intradermal post-exposure prophylaxis regimens, total projected vaccine needs remain similar (about 73 million vials) yet 17·4 million more people are vaccinated, making this an extremely cost-effective method, with costs of US$635 per death averted and$33 per disability-adjusted life-years averted. Scaling up dog vaccination programmes could eliminate dog-mediated rabies over this time period; improved post-exposure prophylaxis access remains cost-effective under this scenario, especially in combination with patient risk assessments to reduce unnecessary post-exposure prophylaxis use. Interpretation: Investing in post-exposure vaccines would be an extremely cost-effective intervention that could substantially reduce disease burden and catalyse dog vaccination efforts to eliminate dog-mediated rabies. Funding: World Health Organization

A mixed methods assessment of knowledge, attitudes and practices related to aflatoxin contamination and exposure among caregivers of children under 5 years in western Kenya

Abstract Objective: Identifying factors that may influence aflatoxin exposure in children under 5 years of age living in farming households in western Kenya. Design: We used a mixed methods design. The quantitative component entailed serial cross-sectional interviews in 250 farming households to examine crop processing and conservation practices, household food storage and consumption and local understandings of aflatoxins. Qualitative data collection included focus group discussions (N 7) and key informant interviews (N 13) to explore explanations of harvesting and post-harvesting techniques and perceptions of crop spoilage. Setting: The study was carried out in Asembo, a rural community where high rates of child stunting exist. Participants: A total of 250 female primary caregivers of children under 5 years of age and thirteen experts in farming and food management participated. Results: Study results showed that from a young age, children routinely ate maize-based dishes. Economic constraints and changing environmental patterns guided the application of sub-optimal crop practices involving early harvest, poor drying, mixing spoiled with good cereals and storing cereals in polypropylene bags in confined quarters occupied by humans and livestock and raising risks of aflatoxin contamination. Most (80 %) smallholder farmers were unaware of aflatoxins and their harmful economic and health consequences. Conclusions: Young children living in subsistence farming households may be at risk of exposure to aflatoxins and consequent ill health and stunting. Sustained efforts to increase awareness of the risks of aflatoxins and control measures among subsistence farmers could help to mitigate practices that raise exposure