OptiMAx Will Test Whether SQ-LNS Incentivises Vaccination Uptake in Rural Chad and Niger, With a Cost Effectiveness Analysis. It Will Also Look at Whether Having Received SQ-LNS Before Becoming Malnourished Leads to Better Outcomes for Children Treated Under the OptiMA Protocol.

Background Malnutrition and infectious disease form a vicious cycle, posing a double threat to vulnerable children in low- and middle-income countries. Malnutrition makes children more vulnerable to infectious diseases, while infectious diseases increase the risk of malnutrition. When caught in this cycle, children are far more likely to die or suffer adverse effects on their health and development. High rates of wasting and low immunization coverage also constitute a debilitating double burden for already fragile health systems. Every year, in these contexts, hundreds of thousands of children are treated for severe wasting, while suffering repeated and prolonged epidemics of vaccine-preventable diseases such as measles.

To reverse this dynamic, ALIMA (The Alliance for International Medical Action), a Dakar-based African medical alliance linking national Nongovernmental Organizations (NGOs) and international research institutes, has proposed a research program called OptiMAx to assess the potential impact of joint programming of monthly small-batch lipid-based nutritional supplementation (SQ-LNS) coupled with immunization services, with a particular focus on documenting the evolution of Pentavalent 3 and Measles 1 coverage in the 12-23 month age group.

Rural areas in Niger and Chad are at the center of this dynamic, recording some of the worst indicators of malnutrition, with recurrent epidemics of measles and sporadic outbreaks of diphtheria and whooping cough. Yet only 28.6% of children under the age of two in Ngouri (Chad) and 4% in Mirriah (Niger) have a minimum acceptable diet (1, 2).

Malnutrition indicators and immunization coverage rates in Chad and Niger are among the worst in the world. Stunting and wasting affect 28% and 8.6% of children respectively in Chad, and 47.0% and 12.2% in Niger. Stunting affects 35.7% of children under 5 (U5) in Ngouri, Chad, and 51.5% in Mirriah, Niger. Wasting affects 13.3% and 17.6% of children in Ngouri and Mirriah respectively. Vaccination coverage against measles 1 by card verification and recall of mothers/accompanying adults is 75.1% nationally in Chad and 83.5% in Niger. It is lower in Ngouri in Chad (67.3%) and Mirriah in Niger (74.3%) (1,2).

High rates of wasting and inadequate immunization coverage represent a debilitating double burden for fragile health systems, as in Chad and Niger, where hundreds of thousands of children are treated for severe wasting and repeated, prolonged epidemics of vaccine-preventable diseases such as measles occur.

1.2 Benefits of SQ-LNS supplementation Small-quantity lipid-based nutritional supplements (SQ-LNS) are food supplements designed to prevent malnutrition and improve child survival, growth and development. Lipid-based nutritional supplements are a category of ready-to-use, nutrient-rich food supplements fortified with milk powder, essential fatty acids, vitamins and minerals at levels designed to treat and prevent acute malnutrition.

They can be consumed straight from the package, do not require refrigeration and are safe from bacterial contamination. Ration size and level of enrichment vary according to their use in treating or preventing acute malnutrition. Ready-to-use therapeutic foods (RUTFs) or complementary foods come in 92 or 100 gram sachets, medium LNS in 50 gram sachets and SQ-LNS in 20 gram sachets.

SQ-LNS come in 20-gram sachets and are seen as a way of enriching the local diets of young children to better meet their specific nutrient needs. The recommended dose of one 20 grams sachet per day (at a cost of 0.09 USD per sachet) can be mixed with home-prepared foods or consumed directly from the sachet. SQ-LNS supplementation for children aged 6 to 23 (accompanied by messages to reinforce infant and young child feeding recommendations) is based on solid evidence. Feeding a child a single sachet of SQ-LNS per day for one year can reduce the risk of all-cause mortality by 27% (3), iron-deficiency anemia by 64% (4), severe wasting by 31% (5), and severe stunting by 17% (5). SQ LNS supplementation has also been shown to reduce the proportion of children in the lower range of cognitive development (language, social-emotional and motor scores) by 16-19% (6). Figure 2. The recent World Health Organization (WHO) guideline on complementary feeding of infants and young children aged 6 to 23 months recently recommended the use of SQ-LNS in food-insecure settings, the evidence being deemed "very safe" (7).

Another retrospective study showed that children who had received SQ-LNS supplementation and then been treated for an episode of acute malnutrition under a simplified protocol were associated with fewer hospitalizations than children who had not received SQ-LNS before being treated for cachexia (8, 9).

1.3 Study rationale: why use mass SQ-LNS supplementation as a vaccination incentive? ALIMA has already documented high vaccination coverage in health zones where SQ-LNS is distributed through health centers. Linking SQ-LNS distributions to child growth monitoring and Essential Program on Immunization (EPI) activities in a health center should have a significant impact on vaccination coverage at population level.

A December 2023 Cochrane meta-analysis (10) examined interventions to improve childhood immunization coverage in low- and middle-income countries. The majority of the 41 studies meeting the inclusion criteria were individual or cluster randomized trials examining the impact of health education, the use of patient reminders - particularly by SMS - monetary incentives for families or performance-based payments to health systems. Only one of these studies, by Banerjee et al (11), used food for families to encourage attendance at vaccination sites. The main limitations cited are either single studies with small numbers of participants, or inconsistent results between different studies. Overall, the level of certainty of the evidence is low, and more high-quality studies are needed to inform policy and practice.

In parallel with the Cochrane meta-analysis, Gavi and the Eleanor Crook Foundation (ECF) published "A literature review and proposed learning agenda on Immunization-Nutrition Integration (INI)" in November 2023 (12). The integration of child nutrition and immunization makes sense insofar as the services are provided by the same health personnel and target the same age groups (12). To date, the only established combined intervention is vitamin A supplementation as part of routine EPI or supplementary immunization activities (oral polio vaccination campaigns). The ECF report identifies the optimal conditions for integrating services: overlapping target populations, compatibility of timing and frequency of services, acceptability to families and health workers, similar logistical requirements and level of competence required for health service staff. The intervention identified by the Gavi/ECF report as potentially fitting within these constraints is supplementation with small-quantity lipid-based nutritional supplements (SQ-LNS) as part of routine EPI.

Given the persistent difficulties in achieving Penta3 and first dose of measles-containing vaccine (MCV1) vaccination coverage high enough to reduce the frequency of epidemics, the implementation of a project to encourage EPI adherence is particularly relevant for children in the 6-11 month age bracket, which is also the optimal age for the initiation of SQ-LNS supplementation. The hypothesis is that the inclusion of SQ-LNS distribution in the EPI for this age group will significantly increase Penta 3 and measles vaccination coverage in high-risk, high-burden and hard-to-reach areas in West and Central Africa.

1.4 Potential barriers to accessing vaccination or the SQ-LNS supplementation program A range of factors influence access to, or use of, preventive or curative healthcare services at primary level. In both Chad and Niger, barriers to access may include geographical distance or flooding problems, lack of knowledge of available services, or poor quality of the relationship between families and healthcare providers. Investigators consider it essential to study the barriers and facilitators to access to vaccination and participation in the SQ-LNS supplementation program in our study areas.

1.5 Theory of change Our theory of change is that by adding SQ-LNS distributions to routine immunization activities in health centers or even health huts, more children will be vaccinated, particularly against measles, while benefiting from other health services in a cost-effective way. In addition, the distribution of SQ-LNS to children aged 6 to 18 months will reduce the opportunity costs associated with travel to health centers; SQ-LNS will improve the health and development of young children - creating a positive feedback loop that will encourage families to continue to visit the SQ-LNS distribution site; and the inclusion of vaccine-related questions in mid-upper arm circumference (MUAC) family training will provide an additional opportunity to reinforce the importance of immunization for young children's health and well-being. Investigators believe that encouraging to provide quality nutrition to their young children will help overcome the obstacles that prevent them from reaching the health center and health huts (e.g. distance, lack of knowledge of the vaccination schedule, etc.), which contribute to the number of under-vaccinated children in Ngouri, Chad and Mirriah, Niger.

SQ-LNS distributions also provide repeated opportunities to educate caregivers on the importance of vaccinations and tackle vaccine hesitancy, thereby improving on-time or catch-up vaccination coverage. At the same time, SQ-LNS will address key nutrient deficiencies in children's diets, improving growth and development outcomes. In the short to medium term, this will deliver more effective services to more people, while reducing the burden of malnutrition and infectious disease, and the costs associated with responding to both. In the long term, fewer measles infections, cases of acute malnutrition, hospitalizations, anemia and growth/development will mean lives saved, lives improved and a less overwhelmed, more cost-effective healthcare system.

1.7 History of ALIMA's Optimizing treatment of malnutrion (OptiMA) projects In 2022, acute malnutrition (AM) affected 45 million children under the age of 5 worldwide, including 13.7 million children suffering from the most severe form. (13) Nearly half of all deaths in children under the age of 5 are linked to undernutrition, which is also the main risk factor for loss of disability-adjusted life years in low- and middle-income countries. (14, 15) An estimated 4.6 million children worldwide with AM reside in West Africa, including 275,000 in Chad and 560,000 in Niger. (13)

Although effective treatment exists, coverage of treatment for severe acute malnutrition (SAM) and moderate acute malnutrition (MAM) is low overall, partly because different protocols and products are used in separate programs. (16) New approaches are being studied that define MAM as MUAC\<125 mm or edema, and treat severe and moderate cases with RUTFs at a reduced dosage as the child's condition improves.

OptiMA is one such strategy, which includes: training families to use MUAC tapes to detect early signs of malnutrition in their children; admitting children for treatment in cases of MUAC \<125 mm or edema; and treating all children with SAM or MAM with a single product, RUTF, at a progressively reduced dose as the children's condition improves under treatment. OptiMA showed promise both in a randomized controlled trial in the DRC, which included a demonstration of non-inferiority among the subgroup of children admitted under the current WHO definition of SAM, and in prospective observational cohorts in Burkina Faso and Niger. (17-20)

Other simplified and combined protocols using the same admission and discharge criteria but a diff

• In Ngouri, Chad : Change from baseline in the percentage of zero-dose children assessed in an endline vaccination coverage survey. [Срок оценки: One year after the beginning of SQ-LNS supplementation]
• In Mirriah, Niger: Change from baseline in the percentage of children receiving the first dose of measles vaccine assessed in an endline vaccination coverage survey. [Срок оценки: One year after the beginning of SQ-LNS supplementation]
• In both sites: Change from baseline in the percentage of children receiving the second dose of measles vaccine assessed in an endline vaccination coverage survey. [Срок оценки: One year after the beginning of SQ-LNS supplementation]
• In both sites: Change from baseline in the percentage of children who received all three doses of Pentavalent vaccine assessed in an endline vaccination coverage survey. [Срок оценки: One year after the beginning of SQ-LNS supplementation]
• In both sites : Change from baseline in the timeliness of the first dose of measles vaccinations assessed in an endline vaccination coverage survey. [Срок оценки: One year after the beginning of SQ-LNS supplementation]
• In both sites: Change from baseline in the percentage of children who have received three doses of malaria vaccine assessed in an endline vaccination coverage survey. [Срок оценки: One year after the beginning of SQ-LNS supplementation]
• In both sites: Comparison of mid-upper arm circumference (MUAC) in children 12-23 months of age at baseline and endline assessed in an endline vaccination coverage survey. [Срок оценки: One year after the beginning of SQ-LNS supplementation]
• In both sites: Comparison of treatment outcomes for children 6-23 m of age who received SQ-LNS before being treated for acute malnutrition versus those who did not assessed in an anonymous, individualized database. [Срок оценки: One year after the beginning of SQ-LNS supplementation]