COVID-19 vaccination strategies in settings with limited rollout capacity: a mathematical modelling case study in Sierra Leone.

BACKGROUND: COVID-19 vaccine coverage in low- and middle-income countries continues to be challenging. As supplies increase, coverage is increasingly becoming determined by rollout capacity. METHODS: We developed a deterministic compartmental model of COVID-19 transmission to explore how age-, risk-, and dose-specific vaccine prioritisation strategies can minimise severe outcomes of COVID-19 in Sierra Leone. RESULTS: Prioritising booster doses to older adults and adults with comorbidities could reduce the incidence of severe disease by 23% and deaths by 34% compared to the use of these doses as primary doses for all adults. Providing a booster dose to pregnant women who present to antenatal care could prevent 38% of neonatal deaths associated with COVID-19 infection during pregnancy. The vaccination of children is not justified unless there is sufficient supply to not affect doses delivered to adults. CONCLUSIONS: Our paper supports current WHO SAGE vaccine prioritisation guidelines (released January 2022). Individuals who are at the highest risk of developing severe outcomes should be prioritised, and opportunistic vaccination strategies considered in settings with limited rollout capacity.

Assessing the potential impact of COVID-19 booster doses and oral antivirals: A mathematical modelling study of selected middle-income countries in the Indo-Pacific.

Continued efforts to reduce the burden of COVID-19 require the consideration of additional booster doses and emerging oral antivirals. This study explored the individual- and population-level impacts of booster dose and oral antivirals in Indonesia, Fiji, Papua New Guinea, and Timor-Leste. Our mathematical model included age structure, vaccine coverage, prevalence of comorbidities, and immunity from prior infection fit to incidence data from our study settings. We explored a range of eligibility criteria and found that boosters had the largest impact per dose when prioritised to high-risk adults and adults who had not previously received a booster. Antivirals were most effective in settings with low vaccine-derived immunity. In general, fewer antivirals than booster doses were required to prevent a hospitalisation or death. Only in settings with very high vaccine uptake was the impact per dose of providing booster doses to high-risk adults comparable to providing oral antivirals to high-risk adults. Together, booster doses and oral antivirals could prevent 80%, 64%, 49%, and 65% of deaths, and 38%, 37%, 16%, and 34% of hospitalisations in Fiji, Indonesia, Papua New Guinea, and Timor-Leste respectively. Therefore, our findings support the continued provision of COVID-19 booster doses to high-risk adults in 2023, and advocate for increased access to oral antivirals, especially in settings with low vaccine coverage such as Papua New Guinea. Future work should consider the threshold at which self-financing of COVID-19 oral antivirals would be viable for middle-income countries in South-East Asia and the Pacific.

Cost-effectiveness analysis of a maternal pneumococcal vaccine in low-income, high-burden settings such as Sierra Leone.

Maternal pneumococcal vaccines have been proposed as a method of protecting infants in the first few months of life. In this paper, we use results from a dynamic transmission model to assess the cost-effectiveness of a maternal pneumococcal polysaccharide vaccine from both healthcare and societal perspectives. We estimate the costs of delivering a maternal pneumococcal polysaccharide vaccine, the healthcare costs averted, and productivity losses avoided through the prevention of severe pneumococcal outcomes such as pneumonia and meningitis. Our model estimates that a maternal pneumococcal program would cost $606 (2020 USD, 95% prediction interval 437 to 779) from a healthcare perspective and $132 (95% prediction interval -1 to 265) from a societal perspective per DALY averted for one year of vaccine delivery. Hence, a maternal pneumococcal vaccine would be cost-effective from a societal perspective but not cost-effective from a healthcare perspective using Sierra Leone's GDP per capita of $527 as a cost-effectiveness threshold. Sensitivity analysis demonstrates how the choice to discount ongoing health benefits determines whether the maternal pneumococcal vaccine was deemed cost-effective from a healthcare perspective. Without discounting, the cost per DALY averted would be $292 (55% of Sierra Leone's GDP per capita) from a healthcare perspective. Further, the cost per DALY averted would be $142 (27% GDP per capita) from a healthcare perspective if PPV could be procured at the same cost relative to PCV in Sierra Leone as on the PAHO reference price list. Overall, our paper demonstrates that maternal pneumococcal vaccines have the potential to be cost-effective in low-income settings; however, the likelihood of low-income countries self-financing this intervention will depend on negotiations with vaccine providers on vaccine price. Vaccine price is the largest program cost driving the cost-effectiveness of a future maternal pneumococcal vaccine.

Participatory systems science for enhancing health and wellbeing in the Indian Ocean territories.

Objectives: Co-creation of diabetes and obesity prevention with remote communities allows local contextual factors to be included in the design, delivery, and evaluation of disease prevention efforts. The Indian Ocean Territories (IOT) comprise the Christmas (CI) and Cocos Keeling Islands (CKI) and are remote Australian external territories located northwest of the mainland. We present results of a co-design process conducted with residents of IOT using realist inquiry and system mapping. Methods: Interviews with 33 community members (17 CI, 14 CKI, 2 off Islands) on causes and outcomes of diabetes (2020/21) comprising community representatives, health services staff, dietitians, school principals and government administrators. Interviews were used to create causal loop diagrams representing the causes of diabetes in the IOT. These diagrams were used in a participatory process to identify existing actions to address diabetes, identify areas where more effort would be valuable in preventing diabetes, and to described and prioritize actions based on feasibility and likely impact. Findings: Interviews identified 31 separate variables categorized into four themes (structural, food, knowledge, physical activity). Using causa loop diagrams, community members developed 32 intervention ideas that included strengthening healthy behaviors like physical activity, improving access to healthy and culturally appropriate foods, and overcoming the significant cost and availability limitations imposed by remoteness and freight costs. Interventions included relatively unique Island issues (e.g., freight costs, limited delivery timing), barriers to healthy food (e.g., limited fresh food availability), physical activity (e.g., transient workforce) and knowledge (e.g., multiple cultural backgrounds and language barriers, intergenerational knowledge).

Exploring the barriers and enablers of diabetes care in a remote Australian context: A qualitative study.

OBJECTIVE: This qualitative study explored the current barriers and enablers of diabetes care in the Indian Ocean Territories (IOT). METHODS: A constructivist grounded theory approach that incorporated semi-structured telephone interviews was employed. Initial analysis of the interview transcripts used a line-by-line approach, to identify recurring themes, connections, and patterns, before they were re-labelled and categorised. This was followed by axial coding, categorisation refinement, and mapping of diabetes triggers in the IOT. PARTICIPANTS AND SETTING: The IOT, consisting of Christmas Island and the Cocos (Keeling) Islands, are some of the most remote areas in Australia. When compared with mainland Australia, the prevalence of type 2 diabetes in the IOT is disproportionately higher. There were no known cases of type 1 diabetes at the time of the study. Like other remote communities, these communities experience difficulties in accessing health services to prevent and manage diabetes. Twenty health care professionals and health service administrators in the IOT took part in semi-structured telephone interviews held during April-June 2020. Participants included GPs, nurses, dietitians, social and community services workers, school principals, and administrators. The interview questions focused on their perceptions of the current diabetes care in place in the IOT and their views on the challenges of providing diabetes care in the IOT. RESULTS: We identified four main barriers and two main enabling factors to the provision of effective diabetes care in the IOT. The barriers were: (i) societal influences; (ii) family; (iii) changing availability of food; (v) sustainability and communication. The two main enablers were: (i) tailoring interventions to meet local and cultural needs and values; and (ii) proactive compliance with the medical model of care. CONCLUSION: Due to the cultural and linguistic diversity within the IOT, many of the identified barriers and enablers are unique to this community and need to be considered and incorporated into routine diabetes care to ensure successful and effective delivery of services in a remote context.

Cost analysis for "The Magic Glasses Philippines" health education package to prevent intestinal worm infections among Filipino schoolchildren.

Background: Soil-transmitted helminth (STH) infections are a significant public health problem affecting over 900 million people globally. Health education has been shown to complement mass drug administration (MDA) for the control of these intestinal worms. We reported recently results of a cluster randomised control trial (RCT) showing the positive impact of the "The Magic Glasses Philippines (MGP)" health education package in reducing STH infections among schoolchildren in intervention schools with ≤15% STH baseline prevalence in Laguna province, the Philippines. To inform decision making on the economic implications of the MGP, we evaluated the in-trial costs and then quantified the costs of scaling up the intervention both regionally and nationally. Methods: Costs were determined for the MGP RCT conducted in 40 schools in Laguna province. We estimated the total cost and the costs incurred per student for the actual RCT and the total costs for regional and national scale-up in all schools regardless of STH endemicity. The costs associated with the implementation of standard health education (SHE) activities and mass drug administration (MDA) were determined with a public sector perspective. Findings: The cost per participating student in the MGP RCT was Php 58.65 (USD 1.15) but if teachers instead of research staff had been involved, the estimated cost would have been considerably lower at Php 39.45 (USD 0.77). Extrapolating the costs for regional scale-up, the costs per student were estimated to be Php 15.24 (USD 0.30). As it is scaled up at the national level to include more schoolchildren, the estimated cost was increased at Php 17.46 (USD 0.34). In scenario 2 and 3, consistently, labour/salary costs associated with the delivery of the MGP contributed most to overall programme expenditure. Furthermore, the estimated average cost per student for SHE and MDA were Php 117.34 (USD 2.30) and Php 58.17 (USD 1.14), respectively. Using national scale up estimates, the cost of combining the MGP with SHE and MDA was Php 192.97 (USD 3.79). Interpretation: These findings suggest that the integration of MGP into the school curriculum would be an affordable and scalable approach to respond to the continuous burden of STH infection among schoolchildren in the Philippines. Funding: National and Medical Research Council, Australia, and the UBS-Optimus Foundation, Switzerland.

A cost analysis of producing vaccines in developing countries.

Developing country vaccine manufacturers (DCVMs) supply over half of the vaccines used in developing country immunisation programs. Decisions by developing countries to establish vaccine manufacturing should be based on economic viability, however reliable assessments of vaccine production costs are lacking. This study aimed to quantify the cost of establishing vaccine manufacturing facilities and producing vaccines in developing countries. This study estimates vaccine production costs in developing countries based on twelve vaccines produced by eight DCVMs. The results were based on estimates of the capital and operating costs required to establish vaccine manufacturing facilities under three hypothetical scenarios of production scale and scope. Cost patterns were then compared to vaccine prices paid by countries in both industrialized and developing country markets. The cost of producing vaccines in developing countries was estimated to be on average US$ 2.18 per dose, ranging between US$ 0.98 and US$ 4.85 for different vaccine types and formulations. Vaccine costs-per-dose decrease as production scale and scope increase. Cost-per-dose is mainly driven by fixed costs, but at a scale of production over 20 million doses per year it becomes driven by variable costs. Under the three hypothetical scenarios used, costs-per-dose of vaccines produced by developing countries were around 47% lower than vaccine prices in developing-country markets and 84% lower than prices in industrialized-country markets. This study has found that local production of vaccines in developing countries exhibits both economies of scale and economies of scope. The lower costs relative to prices suggests that a producer surplus and potential profits may be attainable in both developing and developed country markets, supporting sustainable production.

What influences government adoption of vaccines in developing countries? A policy process analysis.

This paper proposes a framework for examining the process by which government consideration and adoption of new vaccines takes place, with specific reference to developing country settings. The cases of early Hepatitis B vaccine adoption in Taiwan and Thailand are used to explore the relevance of explanatory factors identified in the literature as well as the need to go beyond a variable-centric focus by highlighting the role of policy context and process in determining the pace and extent of adoption. The cases suggest the feasibility and importance of modeling 'causal diversity'-the complex set of necessary and sufficient conditions leading to particular decisional outcomes-in a broad range of country contexts. A better understanding of the lenses through which government decision-makers filter information, and of the arenas in which critical decisions are shaped and taken, may assist both analysts (in predicting institutionalization of new vaccines) and advocates (in crafting targeted strategies to accelerate their diffusion).

Issues in selection of DTwP-based combination vaccines.

This study examines regulatory, supply, acceptance and financing issues of combinations based on diphtheria-tetanus-pertussis (whole cell) vaccines (DTwP). These combination vaccines are currently produced in Europe mostly for export. Future regulatory oversight issues could have an impact on their availability. Before use of acellular pertussis-containing vaccines, the number of doses of DTwP vaccines offered in response to United Nations agency procurement tenders far exceeded the projected demand. Current demand and supply are converging. Most of that supply comes from developing country manufacturers, a potential new source of combination vaccines as well. The expected development and use of DTwP-based combination vaccines raises antigen allocation issues that could further affect supply. These combination vaccines have strong programmatic advantages, but pose complex selection issues involving disease burden, presentation, and availability of long-term financing. Vaccine price is not the major driving factor. A model examining important selection factors for regional country groupings provides predictions that have been validated by decisions on use of DTwP-based combination vaccines. This model may be useful in providing long-term uptake projections for other combination vaccines.