A framework for stakeholder engagement in the adoption of new antimalarial treatments in Africa: a case study of Nigeria

A framework for stakeholder engagement in the adoption of new antimalarial treatments in Africa: a case study of Nigeria | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A framework for stakeholder engagement in the adoption of new antimalarial treatments in Africa: a case study of Nigeria Olugbenga Ayodeji Mokuolu, Oladimeji Akeem Bolarinwa, Oluwatumobi Racheal Opadiran, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2384829/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Jun, 2023 Read the published version in Malaria Journal → Version 1 posted 7 You are reading this latest preprint version Abstract Introduction: Recent reports of artemisinin partial resistance from Rwanda and Uganda are worrisome and suggest a future policy change to adopt new antimalarials. We conducted a case study on the evolution, adoption, and implementation of new antimalarial treatment policies in Nigeria. The main objective is providing perspectives to enhance the future uptake of new antimalarials, with an emphasis on stakeholder engagement strategies. Methods This case study is based on an analysis of policy documents and stakeholders’ perspectives drawn from an empirical study conducted in Nigeria, 2019–2020. A mixed methods approach was adopted, including historical accounts, review of programme and policy documents, and qualitative in-depth interviews and focus group discussions. Themes for the framework were developed and applied to the case study. Results Based on policy documents reviewed, the adoption of artemisinin-based combination therapies (ACTs) in Nigeria was swift due to political will, funding and support from global developmental partners. However, implementation of ACTs was met with resistance from suppliers, distributors, prescribers, and end-users, attributed to market dynamics, costs and inadequate stakeholder engagement. Deployment of ACTs in Nigeria witnessed more developmental partner support, robust data generation, ACT case-management strengthening and evidence on antimalarial use in severe malaria and antenatal care management. We propose a framework for effective stakeholder engagement for future adoption of new antimalarials or antimalarial treatment strategies. The framework covers the pathway from generating evidence to making treatment accessible and affordable to end-users. It addresses who to engage with, the content of engagement and what strategies would support effective engagement with key stakeholders at different levels of the transition process. Conclusion Early and staged engagement of stakeholders from global bodies through regulatory authorities to end-users at the community level is critical to the successful adoption and uptake of new antimalarial treatment policies. A framework for these engagements has been proposed as a unique contribution to enhancing this process. artemisinin resistance stakeholder engagement artemisinin-based combination therapy framework antimalarial treatment policy Figures Figure 1 Introduction Translation of scientific evidence into policies and interventions is not always straightforward or swift [ 1 ]. One major example is the problematic introduction of new antimalarial therapies in the late 1990s, when all conventional antimalarial monotherapies including chloroquine and sulfadoxine-pyrimethamine (SP) were failing globally due to multidrug resistance [ 2 ]. Expert meetings were conducted at the World Health Organization (WHO) to review evidence, culminating in policy recommendation towards the adoption of new treatment regimens in malaria endemic regions. The experience over the years, however, indicate that neither scientific evidence nor WHO recommendations were sufficient to realize effective adoption, implementation, deployment and uptake of antimalarial treatment policies [ 3 – 5 ]. There are numerous other drivers, often unique to individual countries, that influence the adoption of antimalarial treatment policies [ 5 ]. One major driver is the impact of country-level stakeholders’ engagement [ 6 ]. Operationalizing evidence into practice does not end with policymakers; engagement with all stakeholders (e.g regulators, suppliers, prescribers and end-users) starting from early stages of evidence generation to the final stage of uptake is central. [ 6 , 7 ]. This manuscript is predicated on current evidence from Southeast Asia [ 8 ] regarding resistance to artemisinin and partner drugs with resultant failure of (ACTs) and the recent reports of artemisinin partial resistance from three African countries [ 9 – 12 ]. Widespread artemisinin resistance in African countries could lead to a rise in the disease burden with devastating impact on mortality similar to events in the 1990s [ 13 ]. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) remain efficacious for treatment of uncomplicated P. falciparum malaria in Nigeria and most African regions [ 14 ] [ 15 , 16 ]. There are however, reports of ACT failure reported from Burkina Faso, Angola and the Democratic Republic of Congo, which are debated [ 17 – 21 ]. New classes of antimalarial therapies are being developed [ 22 , 23 ], but they are at least 5 years away from market introduction [ 23 , 24 ]. The WHO has recently proposed new strategies to address antimalarial drug resistance in Africa, which include better leveraging existing tools to preserve the therapeutic life of current ACTs until other viable solutions become available [ 12 ]. Suggestions include exploring the potential of rotating ACTs before high treatment failure rates are detected, deploying multiple first-line therapies at the same time, and extending the duration of treatment regimens [ 12 ]. Additionally, triple artemisinin-based combination therapies (TACTs), where artemisinin is combined with two carefully selected, widely-used partner drugs is also proposed and being investigated as a possible strategy to prevent or delay artemisinin resistance from emerging [ 24 – 29 ]. All these strategies will require policy change, the context of which may be more complex depending on the type of treatment, required delivery methods, and health system variabilities among others. To aid this potential new transition, lessons learnt during previous transitions to new antimalarial drugs are discussed here. We envision they will inform future policy change to adopt new antimalarials with an emphasis on strategic stakeholder engagement and other social determinants associated with the stakeholders’ mobilization. We conducted a study on the evolution and adoption of antimalarial treatment policy processes and the change of antimalarial implementation processes in Nigeria with the objective of providing perspectives that will enhance future successful uptake of important new antimalarial treatments or treatment strategies in an age of artemisinin resistance. Methods This study is based on two approaches An analysis of stakeholders’ perspectives extracted from a qualitative study conducted in Nigeria between December 2019 and June 2020 involving 33 in-depth interviews (IDI) and 6 focus group discussions (FGDs) [ 30 ]. An analysis of programme and policy documents and two further interviews conducted in December 2021 to include historical accounts with key informants immersed in the malaria elimination program in Nigeria. We adopted mixed methods involving qualitative (IDIs, key informant interviews and FGDs) data from major malaria stakeholders in Nigeria, including policy makers, regulators, manufacturers/distributors, prescribers, researchers, and end-users at community level and review of documents. Qualitative study The qualitative phase of the study conducted with purposively selected respondents in both the federal capital city of Nigeria, Abuja and in a North-central State, Kwara, has been described previously, [ 25 , 26 , 30 ]. For this case study, we extracted information from the 33 IDIs and 6 FGDs with key stakeholders (Table 1 ). The study combined narrative and phenomenological strategies in qualitative enquiry. Key informant interviews Two in-person interviews (~ 2 hours each) were conducted with key informants immersed in the malaria elimination program in Nigeria. There were further rounds of interviews with one of the key informants for further clarification and information via phone calls. The key informants were malaria experts and researchers whose experience spanned over 25 years in malaria control in the country. The interviews were tape-recorded to secure an accurate account of the conversations and avoid data loss. Table 1 Summary of IDIs and FGDs Stakeholder group Respondent interviewed Number interviewed IDI/FDG Policy National regulatory authority officials 5 IDI State malaria control program officials 4 IDI Regulatory NAFDAC official 1 IDI NMEP private sector desk 1 IDI Distributor Public sector drug wholesalers/distributors 4 IDI Private sector wholesalers/traders 4 IDI Health service providers Public sector: clinicians, pharmacists 5 IDI Private sector: clinicians, nurses, pharmacists, drug store 6 IDI Village health workers 2 FGD Malaria Experts/Researchers Immersed experts in Nigeria NMEP 2 Key informant End users Parents / caregivers 2 FGD Parents/ caregivers 3 IDI Community leaders 2 FGD NAFDAC: National Agency for Food and Drug Administration and Control NMEP: National Malarial Elimination Programme Document analysis To trace the evolution and adoption of antimalarial treatment policy processes and the change of implementation processes, we searched online and screened programmatic, malaria treatment guidelines and policy-papers for relevance to antimalarial policy change adoption. Boolean operators were used to narrow our search to the relevant documents from PubMed, African Journal online, Federal Ministry of Health website, WHO websites and Malaria Elimination Programme websites. The keywords used for the search were antimalarial, policy, stakeholders’ engagement , artemisinin combination therapy, resistance, therapeutic efficacy and Nigeria. Of the 50 documents identified, 9 were relevant to the study and included in the analysis. The findings from the policy document review were triangulated with the thematic construct of the qualitative data to assess stakeholders’ engagement in the adoption of new antimalarial treatment strategies in Nigeria. Results And Discussion Nigeria malaria control architecture Nigeria has a population of over 200 million and the highest burden of malaria infections in Africa [ 31 ]. The Federal Ministry of Health (FMoH) through the National Coordinator is responsible for malaria control and elimination activities in the country [ 32 ]. The National Food and Drug Administration Control (NAFDAC) is responsible for regulatory function of malaria drugs and commodities. The Pharmaceuticals Manufacturing Group (PMG) plays an important role in the production of malaria commodities either independently or serving as franchise for local companies. The Nigerian health system operates a three-tier arrangement consisting of the Federal, State and Local authorities. The federal level formulates policy and controls the tertiary care. The states and local government levels are responsible for implementation of the policy. They are also responsible for regulatory, and implementation of activities related to secondary and primary levels of care respectively. Malaria service delivery, especially case management is channeled through public community and private systems. Health insurance coverage is low. Provision of antimalarials in public primary healthcare facilities is largely free or heavily subsidized while the private system is largely fee for service except few enlisted in health insurance schemes [ 33 ]. Doctors are the primary prescribers in the tertiary facilities and to a large extent in the secondary levels [ 33 ]. Various other health professionals serve as prescribers in some secondary facilities and mostly in primary health care facilities. There is also a large informal system consisting of Proprietary Patent Medicine Vendors (PPMVs) and Community Pharmacists as prescribers. Malaria burden and treatment policy in Nigeria Nigeria, with about 63 million annual cases of malaria, accounts for the largest burden of malaria globally; 26.8% and over 31.9% of the 241 million global malaria disease case and 627,000 deaths respectively [ 34 ]. The incidence of malaria in Nigeria reduced from 373 per thousand in 2010 to 314 in 2020 [ 35 , 36 ]. The prevalence from Malaria Indicator Surveys in children 2–10 years has shown a decline from 42%[ 37 ] in 2010 to 23% in 2018[ 35 ]. The current National Malaria Strategic Plan (NMSP 2021-25) has adopted a stratification approach to tailor actions in relation to peculiar characteristics of malaria within the various geo-political zones of the country. Since 2004, the treatment policy of malaria in Nigeria evolved from monotherapies to ACT [ 38 ]. Additionally, injectable artesunate for severe malaria and chemo-preventive strategies involving the use of intermittent preventive treatments in pregnancy (IPT) and seasonal malaria chemoprevention (SMC) were also adopted [ 38 ]. Thus, the country provides a rich experience of different cycles of translational policies on antimalarials for key lessons and adoption of best practices. Stakeholder engagement in adoption of antimalarial policy change Due to the spread of resistance to antimalarial monotherapies in the 1990s, the WHO, commissioned a review of literature in which evidence on resistance to chloroquine and other monotherapies was collected and assessed [ 2 , 33 ]. These meetings resulted in the WHO recommendation to switch to ACTs as global first-line therapy for the treatment of uncomplicated falciparum malaria [ 39 ]. Although most endemic countries followed this recommendation and adopted ACTs in their national guidelines, significant delays were experienced between updated guidelines and the actual implementation [ 40 , 41 ]. Individual countries usually appraise the recommendations of the WHO to reconsider their country-level strategies. Changing first-line therapies however involves a wide range of stakeholders at different levels of the healthcare system [ 5 ]. Stakeholder engagement in health policy is therefore critical for translating evidence into policy and implementation [ 42 , 43 ]. An immersed expert recounted ” ……a major challenge in the adoption of change in monotherapy is that the scope of stakeholder engagement is often not well-defined and supported by evidence. Furthermore, tailoring the stakeholder engagement strategies based on learning or analysis of the various stakeholders’ audiences are not well described.” (Interview Expert2) When stakeholder engagement is not well coordinated the messaging also becomes fragmented and unclear [ 42 , 43 ]. From our case scenario, we developed a framework (Fig. 1 ) for stakeholder engagement in the introduction and deployment of new antimalarials or alternative strategies to treat malaria. This depicts the interrelations of the stakeholders ranging from those who generate evidence on antimalarial therapeutic efficacy at local and international levels down to the antimalarial end-users. The stakeholders include health policy makers, control and regulatory agencies, distributors, marketers and prescribers (Fig. 1 ). We employ the five pillars of International Association of Public Participation (IAP2) [ 44 ] to synthesize five stakeholder engagement spectra to guide stakeholder engagement of new antimalarials or treatment strategies. Evolution of antimalarial policy adoption in Nigeria i. Monotherapy era of pre-2001 Policy documents revealed a historical account of the evolution and adoption of antimalarial treatment policy processes in Nigeria [ 32 , 38 , 39 , 45 ]. These reviews showed an evolution in treatment policies during the era of antimalarial monotherapies. Chloroquine provided relative stability in the use of monotherapy. An immersed expert recalled earliest guidance by the WHO on selection of antimalarials recommending a four-point decision scale in the programmatic deployment of antimalarials "...using these scales; antimalarial treatment failure rate 25% and the antimalaria molecule should be replaced with another that is more efficacious.” (Interview Expert1). In Nigeria, efficacy of chloroquine was prolonged despite resistance reported from Southeast Asia a decade earlier [ 38 ]. However, from 1988, efficacy in Nigeria declined below 70% [ 46 ]. Despite the reduced efficacy of chloroquine, the Nigerian Malaria Control Programme (as it was then called) waited another decade before reacting. This may be related to limited awareness of the WHO policy guidelines by national policy makers. The two experts interviewed opined that an additional factor was the popularity of chloroquine and the perceived concern about the ability of sulphadoxine-pyrimethamine (SP), which was the most viable alternative available, to withstand the same pressure as chloroquine before widespread resistance occurs. Buttressing these fears, was evidence of increasing SP resistance from East Africa where SP had earlier been adopted as the first-line therapy [ 38 ]. While the country was in a dilemma, global discussion on the adoption of ACTs began. After the WHO provided evidence on drug resistance to chloroquine, Nigeria in early 2000 was tending towards adopting SP, the only available monotherapy, as their national first-line antimalarial therapy. ii. Transition era from monotherapy to ACT policy The transition from monotherapy to ACT policy was not a swift process. An immersed expert commented “...until Nigeria engaged in the conversation of ACT adoption, the country mainly reacted to the growing evidence of treatment failure by adopting strategies to increase compliance to the existing monotherapies. Major interventions were the prepackaging of these monotherapies and the introduction of home management of malaria. Furthermore, there was an extensive interaction between WHO, NMEP, the PMG and the regulatory authorities in which consensus was reached that age-specific antimalarial drugs should become available. While the PMG went ahead to implement these changes, the need for ACT as a strategic cornerstone for the treatment of uncomplicated malaria was gaining momentum at international levels.” (Interview Expert1). Therapeutic efficacy studies (TESs) conducted in 2002 showed that the corrected adequate clinical and parasitological response (ACPR) for chloroquine and SP in Nigeria were abysmally low at 34.7% and 57.4% respectively [ 38 ]. An immersed expert recalled these worrying developments, “…The NMEP identified the next stage of the decision-making of selecting the most appropriate ACT. This was reported as the decision of another stakeholder meeting held in 2004.” (Interview Expert1). The communique of that meeting emphasized the prevalence of both chloroquine and SP resistance in the country, the proven efficacies of the new ACTs as reported from other countries and the need to conduct a local TES on the candidate ACTs (artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ)) to inform programmatic deployment. Hence, another TES was conducted in 2004 that indicated efficacies above 90% for both ACTs for the treatment of uncomplicated falciparum malaria [ 38 ]. Due to the availability of AL as a co-formulated drug and high level of tolerability, the country adopted AL as the new first-line antimalarial while ASAQ, though a co-first line was reserved as an alternative or provided only by some donors as a cheaper alternative to support care in some areas of the country [ 38 ]. An immersed expert narrated “…this decision of the country, despite its intent, did not engage the PMG at any point. It was therefore regarded as a betrayal of the trust that has been built with the PMG. They complained of significant economic loss from the investments made to re-tool and re-register the newly prepackaged monotherapies. The result was that of a significant push back through intense advertisement of monotherapies by the PMG and the lack of uniformity in malaria treatment messaging. The FMoH had to set up a special committee to interphase and handle the change of management process. These issues delayed implementation of ACT use despite the relative early adoption of the ACT policies. Furthermore, several states did not include ACTs in their essential medicine lists and could therefore not invest in the ACTs. In addition, the National Health Insurance Scheme (NHIS) also continued to recommend the use of monotherapies because the capitation fees being charged was significantly related to cost of monotherapies since fever/malaria was the commonest reason for outpatient consultations” (Interview Expert1). The important lesson learned is that the PMG and NHIS were not adequately engaged as stakeholders in the policy change procedure, leading to inefficient deployment. The same applied for marketers and distributors who had previously invested and engaged in alternative therapies and were not compensated for these investments. There was a long delay before the prescribers had awareness of the policy change because of poor downstream communication to these stakeholder groups. ACT policy implementation and lessons learnt Following the adoption phase, Nigeria rolled out implementation of ACT immediately. This was shorter than the average time-lag of 12–18 months between policy adoption and implementation as reported from endemic regions [ 47 , 48 ]. Although Nigeria encountered some delays in evidence uptake until policy adoption (between 2001 and 2005), this was compensated for by zeal and political will to implement ACT as new treatment regimen. This was in turn reinforced by funding from the global developmental partners [ 40 ]. However, there was an immediate push-back among the pharmaceutical companies who had hitherto invested heavily on age-specific pre-packaged chloroquine [ 49 , 50 ] and those already co-formulating SP for a large demand for Eastern Africa [ 42 ]. The implementation strategies were also met with resistance from suppliers, distributors, prescribers, and the end-users. Multiple reasons were adduced for the initial apathy [ 51 ]. The antipyretic effects of chloroquine that gave immediate relief to the patients and a sense of effectiveness to the prescribers and the suppliers created a sustained demand for chloroquine. A policy maker mentioned “…the resistance from the private sector who probably at that particular time have invested their resources to produce these monotherapy drugs and were not carried along when this policy of changing to ACT combination drugs came, they were not properly orientated.” (IDI POLREG05). Other respondents noted that stakeholder engagement with regulatory agencies such as NAFDAC is essential for the adoption of antimalarial treatments. Failure to engage them could lead to delays in the adoption process. A policy maker mentioned “The NAFDAC plays important role in regulation of the newly introduced antimalaria drugs in the country. So, NAFDAC is at the point of entry of any product, irrespective of which program is advancing for such products, NAFDAC need to accredit such drugs. And if that is not done, then there is every tendency that such drug will not be allowed at the program level.” (IDI POLREG02). Another factor was the cost of chloroquine compared to ACT. In low-income settings like Nigeria, affordability, and accessibility to ACT is crucial. The global supply and demand shortfall for ACT became an immediate burden that warranted WHO, UNICEF and other developmental partners outsourcing the procurement of ACT for the public sectors in the endemic regions, Nigeria inclusive [ 39 , 40 ]. Evidence from Nigeria in the early period of policy adoption and implementation revealed mixed reports on the problematic transition to ACT in Nigeria. Some end-users and prescribers interviewed cited challenges related to prescribers’ distrust in ACT efficacy compared to the well-known chloroquine, while patients reported discomforting side-effects to amodiaquine. The post-adoption phase of ACT deployment in Nigeria witnessed more developmental partner support for malaria control activities, robust data generation from efficacy studies and subsequent programme evidence. The ACT case-management strengthened with backup of this evidence then became established in treatment guidelines [ 38 , 52 ]. In addition, chemoprevention in pregnancy and seasonal campaigns for malaria prevention among under 5-year old children were also introduced [ 52 ]. One major fall-out of the post-adoption was the monopoly of the ACT supply by the pharmaceutical industry while global efforts were compelled to patronize the monopoly. This was detrimental to the survival of the local pharmaceutical industries who had previously been major stakeholders in the policy change adoption in Nigeria. To solve this problem and to reduce the high costs of ACTs among the populations in the endemic countries, the global efforts in 2008 developed the Affordable Medicine Facility-malaria (AMFm) which was piloted in seven African countries including Nigeria [ 53 ]. This policy attempted to supply ACT at a more affordable rate to the public and private systems through the principle of first line buyers who bought at a highly subsidized rate, and they were allowed a limited profit margin to make the ACTs affordable. After the pilot phase of the AMFm, the scale up was implemented under the nomenclature of Private Sector Co-payment Mechanism (PSCM). The operational model was essentially similar except that there was increasing prettification of the first line buyers in the private sector responsible for a fraction of the cost of the ACTs [ 54 ]. The PSCM intervention had an initial positive impact on availability of ACTs which increased significantly over the period of implementation [ 54 ]. The impact was observed particularly among PPMVs with associated increased access to ACT by the poor households [ 54 ]. But similar to previous subsidized public health interventions, the programmes were not sustainable [ 53 ]. Another limitation was that important stakeholders in the downstream of ACT policy uptake were completely neglected [ 55 ]. Therefore, this evidence-based novel intervention was discontinued. Nevertheless, AMFm/PSCM still leaves a regulated supply chain for malaria in Nigeria including a stabilized ACT cost. Stakeholder groups reported that inadequate stakeholder engagement at all levels led to the poor uptake of the policy. They suggested that these should be addressed to support the adoption of future antimalarial treatments: “To ensure that all important stakeholders are involved in such important public health intervention, we need to support it with advocacy, communication, mobilization, and sensitization. So, if we just deploy without following it up or without backing it up, we know the Behavioural Change Communication (BCC) component of our general attitude is difficult to attain.” (IDI POLREG03). The lesson learned was that private sector engagement was challenging since negotiated ACTs were largely available through the public sector. As with PMG, the private sector was hindered following the sudden withdrawal of both the AMFm and PSCM. There was also a mismatch in policy to diagnostically confirm each suspected case of malaria and the actual availability of diagnostic tools. Moving forward and recommendation Following the general principles, there is need for stakeholders’ identification/mapping, identification of the policy issues and purpose to engage the stakeholders [ 44 ]. Thereafter, strategies of engagement that take into consideration the local and socio-cultural peculiarities are important for an indigenous disease like malaria. Lastly, predetermining measurable policy adoption outcomes and achievable benefits must be set. For engagement to be very effective, some respondents suggested that the content of messaging and communication regarding the rationale for a change in policy has to be well adapted to the peculiarities of the stakeholders. “ They will be able to tell people the benefits of the [new] drugs.” (End-user FGD 01). “…we give them health education about the drug, we should train the community….“ (Suppl FGD 01) A number of communication channels were recommended as effective strategies for communicating the rationale for a change in policy. Below are extracts of some of the narratives from the stakeholders; “The government should help us announce very well on the radio and when something like this is available, they should inform the king of the community. He will find a way to disseminate information either through mosque or church when the government announce on the radio. They should tell the King and he will inform the people”. (End-user FGD 05). “…... in the olden times, we used the town crier…. so, I think we can use the same means. Each community will decide what to do. Some use mosques, some use churches, they will make the announcement there”. (End-user FGD 05). “If you can embark on door-to-door awareness they will readily accept it”. (End-user FGD 06). “Whenever you identify the leaders within that community, there's always a particular leader in each section of the community, they will accept it”. (End-user FGD 04). “Maybe Pastors of the church, the Imam and Alfas and the schools and the clinic, the health workers they would also play a very big role to make sure that the community accepts the drugs” (IDI End-user 03). Several stakeholders highlighted the importance of making training of health workers an integral part of the deployment process. They suggested that building the capacity of health workers would enable them to provide the right information about rationale for deployment of any new treatments at the community level. Policy makers suggested “ People should be enlightened about the drug; they should know the composition of the drug and know the side effects too so that there will be no resistance.” (IDI POLREG08). Another regulatory authority mentioned “They should train them about the new drug that is coming, the composition of the drug, we can hold a seminar or workshop to boost their capacity.” (IDI REG 08). These views were also shared by suppliers “ There should be seminar for health workers, they should pay people for attending the seminar.” (Suppl FGD 02) Engagement with end-users is required for successful adoption of any new antimalarial policy as summed up by a respondent: “There are gatekeepers within the community; it could be traditional ruler, it could be a philanthropist within that community that is well respected and that may have contributed to the development of that environment in one way or the other, so they are key.” (IDI REG01). The perspectives of end-users suggested that there are several reasons why engagement should be an integral part of the having adequate knowledge of any new antimalarial treatment. End-users stated reasons for the engagement: “if they are informed before that if you take this drug, this is the problem, then they will not worry” (End-user FGD 01). Another end-user buttressed this: “Since we all know that initially, so definitely every drug that will be highly effective must come with side effects. So, they should tell the community this is the side effect of this drug.......” (End-user FGD 01). Most end-users suggested that engagement processes that seeks to address issues related to health-seeking behaviour should be adopted: “So I think one of the strategies is to have an early engagement of the local communities, their health-seeking behaviour ultimately influences whatever you are doing, we can reduce all of those obstacles.” (End-User IDI01,). Other respondents during discussion gave insight into drug non-adherence because of lack of end-user engagement “I don’t normally complete the dosage. Once I feel much better, I stop using it.” (End-user FGD 04). “...well we have this mentality of being doctors in the house before going to the medical doctor, we treat with paracetamol and when the patient is not responding we go to the counter to get some malaria drugs like Lonart, so that is what we do primarily but if there is no response we now go to the hospital to see medical doctor.” (End-user IDI 03). Policy makers and regulators (e.g NAFDAC) should be engaged through adequate, convincing, and locally acceptable evidence. This will give credibility and fidelity to the new antimalarial. As narrated in the policy change era to ACT, the private sector distributors, marketers, and prescribers will play key roles if engaged earlier. Engagement of health practitioners is essential for a transition to a new antimalarial drug or treatment strategy. Several respondents anticipated challenges in private sector, where retailers and prescribers are often guided by patient demand rather than treatment guidelines. Especially in the private sector. This was considered a potential barrier to future adoption and would require active engagement of the private sector stakeholders. The same applies to a large number of informal retailers, as ‘over the counter’ prescription without expert consultation remains common in Nigeria [ 56 ]. Some suppliers mentioned that retailers and prescribers are not always aware of the magnitude of drug resistance, its causes and risks, and its implications. Therefore, providing training and information was considered important by some respondents. Such information campaigns should begin with awareness of the threat of antimalarial drug resistance and the risks involved. They should be educated on the benefit of deploying new drugs with a view to delay or prevent multidrug resistance: “So, these are lessons learnt that moving forward, if there's anything of such a nature, and more importantly, when we are at this stage, this is the time we even need to start engaging the patient at the community.” (IDI POLREG05) Learning from the experiences of the transition from monotherapies to ACT, all stakeholder groups shared the view that implementation programs and behavior change initiatives are important to engage practitioners and patients in a prospective transition to a new therapy. The NMEP, under coordination of the Ministry of Health (MoH), was considered the most credible party to coordinate such initiatives in Nigeria. Some policy makers gave examples of models of engagement that have worked in local communities in the provision of health services that could be adopted for engagement regarding the introduction of new antimalarials: “when we initially introduced the ACT, there's one we called role model. In deploying some of these drugs, role model has key roles to play because if you look at it, it takes a patient like 100 mins to move from his house to facility. But within a household, if we have a respected role model within the community, people will believe in him or her than the people that they, maybe, see them once in blue moon whenever they go to the hospital… but these individuals… we need to look at how we engage them.” (IDI POLREG08). Proposed framework for stakeholder engagement in adoption of new antimalarials or treatment strategies From the foregoing, we propose a framework for effective stakeholder engagement for future adoption of new antimalarial treatments or treatment strategies in Nigeria. The framework covers the pathway from generating evidence to making the treatments accessible and affordable to end-users. It also addresses key elements and recommendations on who to engage, the content of engagement and what strategies would support effective engagement with various key stakeholders at different levels of a transition process. The triad of evidence, policy and implementation is envisioned in a well-coordinated stakeholder spectrum with active two-way interrelationships between the stakeholders which will be informed by critically outlined strategies [ 57 ]. Adopting the five pillars of IAP2, [ 44 ] we identified a five-step approach to engage stakeholders as shown below. Inform : provide balanced and objective information on the policy change to the stakeholder in terms of the purpose, opportunities, and limitations of the policy. Consult : obtain feedback from the stakeholder on the assessment and their understanding of the policy change with the view of the local alternatives, challenges, and decisions. Involve : work directly and together with the stakeholders to ensure that their concerns, aspirations and challenges are understood and taken into consideration. Collaborate : reiterate this is a partnership relationship with the stakeholders to take the policy change adoption decision together and to identify preferred best solutions. Empower : place the policy adoption in the hands of the stakeholder for sustainable implementation and feedback. Adapting these to the Nigeria case of antimalarial policy change adoption, we identified critical stakeholders as shown in the conceptual framework (Fig. 1 ). Putting evidence at the top of policy change adoption, which should trigger the subsequent policy directions that led to the efficacy trials and change in the national antimalarial policy in the country. The policy makers must be actively engaged by the WHO and other isolated research while the policy makers in turn inform, consult, and involve other stakeholders like regulators of malarial drugs, the manufacturers, the distributors, the prescribers, and the end-users. Conclusion This paper identified that the historical evolution of antimalarial drug resistance and adopting new therapies spanned several stakeholders’ engagements experiences before, during and after introduction of ACTs. Early and staged engagement of stakeholders from global bodies through regulatory authorities to end-users at the community level is critical to the successful adoption of any new treatment strategy for malaria. A framework for these engagements has been proposed as a unique contribution to enhance this process. Abbreviations ACPR: Adequate clinical and parasitological response ACT: Artemisinin-based combination therapy AL: Artemether-lumefantrine AMFm: Affordable Medicine Facility-malaria ASAQ: Artesunate-amodiaquine BCC: Behavioural Change Communication FGD: Focus Group Discussion FMoH: Federal Ministry of Health IAP2: International Association of Public Participation IDI: In-depth Interview IPT: Intermittent preventive treatment IRB: Institutional Review Board NAFDAC: National Agency for Food and Drug Administration and Control NHIS: National Health Insurance Scheme NMEP: National Malaria Elimination Programme PMG: Pharmaceutical Manufacturing Group PPMVs: Proprietary Patent Medicine Vendors PSCM: Private Sector Co-payment Mechanism SMC: Seasonal Malarial Chemoprevention SP: Sulfadoxine-pyrimethamine TACTs: Triple artemisinin-based combination therapies TES: Therapeutic efficacy studies UNICEF: United Nation Children’s Fund WHO: World Health Organization Declarations Ethics approval and consent to participate Ethical approval from Institutional Review Board (IRB) was obtained from the University of Ilorin Teaching Hospital, Nigeria with approval no: ERC/PAN/2019/07/1916 in addition to ethical approval from Oxford Tropical Medicine Research Ethics Committee (OxTREC Ref: 552-19). Prior to entering the research sites, permission to carry out the study was obtained from relevant community gate keepers, and the respondents before commencement of the interview session. Before administration of the questionnaire, the nature, purpose and process of the study were explained to the participants after which informed written consent was obtained. Necessary steps were taken to ensure confidentiality. Participants were continuously reminded of their right to withdraw from the study at any time. After each session, the participants were consulted to ensure that study findings reflected their voices and perceptions. Consent for publication For the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. Availability of data and materials There are ethical and legal restrictions to sharing our data publicly but they are available upon request from MORU Data Access Committee (https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing). Most interviews are directly traceable to individual identities and therefore we cannot share the interview data without releasing the identities of the respondents. In each interview, respondents introduced themselves and spoke about their direct (working) environment. Moreover, the topics discussed and responses to questions, could be directly linked to their job positions and affiliation, especially with higher level policy and regulatory officials. We guaranteed full anonymity to the respondents prior to data collection and therefore sharing the dataset without restrictions would be unethical. Competing interests We declare that no competing interests exist. Funding We are grateful to UK aid and the UK Government’s Foreign, Commonwealth & Development Office for financial support. This research was funded in whole, or in part, by the Wellcome Trust [220211]. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Authors’ contributions Conceptual design and protocol development – OAM, BOA, PT, CA, FdH, MD, PYC, AMD Field activities (Questionnaire development and validation, interviews and FGDs)- OAM, BOA, PT, FdH, ORO, HAA, CA, PYC Data transcription and coding – OAM, BOA, ORO, HAA, PT, FdH, CA, PYC Drafting, review and editing of Manuscript – OAM, BOA, ORO, HAA, PT, FdH, CA, PYC, MD, AMD, Acknowledgements. We are grateful to the National Malaria Elimination Programme officers, the Regulatory Agency (NAFDAC) and all the stakeholders in Nigeria who participated in this study. References World Health Organization. Global technical strategy for malaria 2016–2030. World Heal Organ [Internet]. 2016;1–35. Available from: https://apps.who.int/iris/bitstream/handle/10665/186671/9789243564999_spa.pdf?sequence=1 Bosman A, Delacollette C, Olumese P, Ridley R, A R, Shretta R, et al. The use of antimalarial drugs: Report of an informal Consultation. WHO & Graficim. 2001. Humphreys K, Piot P. Scientific evidence alone is not sufficient basis for health policy. Vol. 344, BMJ (Online). 2012. Webster J, Hoyt J, Diarra S, Manda-Taylor L, Okoth G, Achan J, et al. Adoption of evidence-based global policies at the national level: Intermittent preventive treatment for malaria in pregnancy and first trimester treatment in Kenya, Malawi, Mali and the Gambia. Health Policy Plan. 2020;35(10):1364–75. de Haan F, Moors EHM, Dondorp AM, Boon WPC. Market Formation in a Global Health Transition. Environ Innov Soc Transitions. 2021 Sep 1;40:40–59. Toe P, Journal M, Toe LP, Dicko B, Linga R, Barry N, et al. Operationalizing stakeholder engagement for gene drive research in malaria elimination in Africa — translating guidance into practice. Malar J [Internet]. 2022;1–16. Available from: https://doi.org/10.1186/s12936-022-04241-3 Adeyemo AO, Aborode AT, Bello MA, Obianuju AF, Hasan MM, Kehinde DO, et al. Malaria vaccine: The lasting solution to malaria burden in Africa. Ann Med Surg [Internet]. 2022;104031. Available from: https://doi.org/10.1016/j.amsu.2022.104031 Phyo AP, Nosten F. The Artemisinin Resistance in Southeast Asia: An Imminent Global Threat to Malaria Elimination. In: Manguin S D V, editor. Intech [Internet]. Towards Ma. London: IntechOpen; 2018. p. 15–39. Available from: https://www.intechopen.com/chapters/60988 doi: 10.5772/intechopen.76519 White NJ. Emergence of Artemisinin-Resistant Plasmodium falciparum in East Africa. N Engl J Med [Internet]. 2021 Sep 23;385(13):1231–2. Available from: http://www.nejm.org/doi/10.1056/NEJMe2110659 Balikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana S-I, Yamauchi M, et al. Evidence of Artemisinin-Resistant Malaria in Africa. N Engl J Med [Internet]. 2021 Sep 23;385(13):1163–71. Available from: http://www.nejm.org/doi/10.1056/NEJMoa2101746 Uwimana A, Umulisa N, Zhou Z. Articles Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda : 2021;(April). WHO. Strategy to respond to antimalarial drug resistance in Africa. WHO/UCN/GMP/202204 [Internet]. 2022;04(June). Available from: https://cdn.who.int/media/docs/default-source/malaria/who-antimalarial-drug-resistance-strategy-for-consultation.pdf?sfvrsn=9d4eaa0_6 Trape JF. The public health impact of chloroquine resistance in Africa. Am J Trop Med Hyg [Internet]. 2001 Jan 1 [cited 2022 Sep 18];64(1_suppl):12–7. Available from: https://www.ajtmh.org/view/journals/tpmd/64/1_suppl/article-p12.xml Sowunmi A, Akano K, Ntadom G, Ayede AI, Ibironke FO, Aderoyeje T, et al. Therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated Plasmodium falciparum malaria -associated anaemia in Nigerian children during seven years of adoption as first-line treatments. Infect Dis Poverty [Internet]. 2017;1–20. Available from: http://dx.doi.org/10.1186/s40249-016-0217-7 WHO-CDS-GMP. Artemisinin resistance and artemisinin-based combination therapy efficacy. 2018. Dorkenoo AM, Yehadji D, Agbo YM, Layibo Y, Agbeko F, Adjeloh P, et al. Therapeutic efficacy trial of artemisinin ‑ based combination therapy for the treatment of uncomplicated malaria and investigation of mutations in k13 propeller domain in Togo , 2012 – 2013. Malar J. 2016;1–9. Gansané A, Moriarty LF, Ménard D, Yerbanga I, Ouedraogo E, Sondo P, et al. Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017–2018. Malar J [Internet]. 2021 Dec 1 [cited 2022 Sep 18];20(1):1–12. Available from: https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03585-6 Dimbu PR, Horth R, Cândido ALM, Ferreira CM, Caquece F, Garcia LEA, et al. Continued Low Efficacy of Artemether-Lumefantrine in Angola in 2019. Antimicrob Agents Chemother [Internet]. 2021 Feb 1 [cited 2022 Sep 18];65(2). Available from: /pmc/articles/PMC7849008/ Rasmussen C, Ringwald P. Is there evidence of anti-malarial multidrug resistance in Burkina Faso? Malar J [Internet]. 2021 Dec 1 [cited 2022 Sep 18];20(1):1–5. Available from: https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03845-5 Rasmussen C, Ringwald P. Continued Low Efficacy of Artemether-Lumefantrine in Angola? Antimicrob Agents Chemother [Internet]. 2021 Jun 1 [cited 2022 Sep 18];65(6). Available from: /pmc/articles/PMC8316127/ Moriarty LF, Nkoli PM, Likwela JL, Mulopo PM, Sompwe EM, Rika M, et al. Therapeutic Efficacy of Artemisinin-Based Combination Therapies in Democratic Republic of the Congo and Investigation of Molecular Markers of Antimalarial Resistance. Am J Trop Med Hyg [Internet]. 2021 Oct 1 [cited 2022 Sep 18];105(4):1067–75. Available from: https://pubmed.ncbi.nlm.nih.gov/34491220/ Tse EG, Korsik M, Todd MH. The past , present and future of anti ‑ malarial medicines. Malar J [Internet]. 2019;1–21. Available from: https://doi.org/10.1186/s12936-019-2724-z Chen, I., Hsiang MS. Triple artemisinin-based combination therapies for malaria : a timely solution to counter antimalarial drug resistance. Lancet Infect Dis. 2022;3099(22 (6)):751–3. van der Pluijm RW, Amaratunga C, Dhorda M, Dondorp AM. Triple Artemisinin-Based Combination Therapies for Malaria – A New Paradigm? Vol. 37, Trends in Parasitology. Elsevier Ltd; 2021. p. 15–24. de Haan F, Bolarinwa OA, Guissou R, Tou F, Tindana P, Boon WPC, et al. To what extent are the antimalarial markets in African countries ready for a transition to triple artemisinin-based combination therapies? Okell LC, editor. PLoS One [Internet]. 2021 Aug 31;16(8):e0256567. Available from: https://dx.plos.org/10.1371/journal.pone.0256567 Tindana P, Guissou R, Bolarinwa OA, Tou F, Haan F De, Dhorda M, et al. PLOS ONE Ethical considerations in deploying triple artemisinin-based combination therapies for malaria : An analysis of stakeholders ’ perspectives in Burkina Faso and Nigeria. 2022;1–15. Available from: http://dx.doi.org/10.1371/journal.pone.0273249 Tindana P, de Haan F, Amaratunga C, Dhorda M, van der Pluijm RW, Dondorp AM, et al. Deploying triple artemisinin-based combination therapy (TACT) for malaria treatment in Africa: ethical and practical considerations. Vol. 20, Malaria Journal. BioMed Central Ltd; 2021. de Haan F, Boon WPC, Amaratunga C, Dondorp AM. Expert perspectives on the introduction of Triple Artemisinin-based Combination Therapies (TACTs) in Southeast Asia: a Delphi study. BMC Public Health [Internet]. 2022 Dec 1 [cited 2022 Sep 18];22(1):1–14. Available from: https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-022-13212-x van der Pluijm RW, Tripura R, Hoglund RM, Pyae Phyo A, Lek D, ul Islam A, et al. Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial. Lancet (London, England) [Internet]. 2020 Apr 25 [cited 2022 Sep 18];395(10233):1345–60. Available from: https://pubmed.ncbi.nlm.nih.gov/32171078/ Tindana P, de Haan F, Mokuolu OA, Guissou R, Bolarinwa OA, Ouedraogo JB, et al. Ethical, Regulatory and Market related aspects of Deploying Triple Artemisinin-Based Combination Therapies for Malaria treatment in Africa: A study protocol. Wellcome Open Res. 2021 Apr 7;6:75. WHO. World Malaria Report 2020: 20 years of global years and challenges. WORLD HEALTH ORGANIZATION; 2020. Federal Ministry of Health. National Malaria Control Programme Strategic Plan 2009-2013: A Road Map for Malaria Control in Nigeria [Internet]. Abuja; 2013. Available from: https://extranet.who.int/countryplanningcycles/sites/default/files/planning_cycle_repository/nigeria/nigeria_draft_malaria_strategic_plan_2009-2013.pdf ACTwatch’Group’and’SFH. ACTwatch’Study’Reference’Document: “The’Federal’Republic’of’Nigeria” Outlet’Survey’ 2015 [Internet]. Washington!DC:!PSI.; 2015. Available from: http://www.actwatch.info/sites/default/files/content/publications/attachments/Nigeria_2015 OS_Reference Document.pdf WHO. World malaria report 2021 [Internet]. Geneva; 2021. Available from: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2021 National Population Commission and ICF. Nigeria Demographic and Health Survey [Internet]. Abuja, Nigeria, and Rockville, Maryland, USA; 2018. 297–305 p. Available from: https://dhsprogram.com/publications/publication-fr359-dhs-final-reports.cfm World Bank Group. Incidence of malaria (per 1,000 population at risk) - Nigeria | Data [Internet]. SH.MLR.INCD.P3. [cited 2022 Sep 18]. Available from: https://data.worldbank.org/indicator/SH.MLR.INCD.P3?locations=NG National Population Commission. Federal Republic of Nigeria. Malaria Indicator Surveys in children 2-10 years [Internet]. Abuja; [cited 2022 Nov 20]. Available from: https://www.google.com/search?q=Malaria+Indicator+Surveys+in+children+2-10+years&client=firefox-b-d&biw=1585&bih=737&sxsrf=ALiCzsbJ8k8k09HIN-2cxhpd32haU9jibw%3A1668946535045&ei=Zxp6Y8u0ApPckgXahpCICA&ved=0ahUKEwiLhPuq3rz7AhUTrqQKHVoDBIEQ4dUDCA8&uact=5&oq= Federal Ministry of Health. National Antimalarial Treatment Guidelines. 2005;(February):1–29. WHO. WHO briefing on Malaria Treatment Guidelines and artemisinin monotherapies - meeting_briefing19april.pdf [Internet]. Geneva; 2006. Available from: https://www.who.int/malaria/publications/atoz/meeting_briefing19april.pdf Bosman A, Mendis KN. A major transition in malaria treatment: The adoption and deployment of artemisinin-based combination therapies. Am J Trop Med Hyg. 2007;77(SUPPL. 6):193–7. Williams HA, Durrheim D, Shretta R. The process of changing national malaria treatment policy: Lessons from country-level studies. Health Policy Plan. 2004;19(6):356–70. Nanyunja M, Nabyonga Orem J, Kato F, Kaggwa M, Katureebe C, Saweka J. Malaria Treatment Policy Change and Implementation: The Case of Uganda. Malar Res Treat. 2011;2011:1–14. Amin AA, Zurovac D, Kangwana BB, Greenfield J, Otieno DN, Akhwale WS, et al. artemisinin-based combinations in Kenya. 2007;11:1–11. Akwanalo C, Njuguna B, Mercer T, Pastakia SD, Mwangi A, Dick J, et al. Strategies for Effective Stakeholder Engagement in Strengthening Referral Networks for Management of Hypertension Across Health Systems in Kenya. Glob Heart [Internet]. 2019 Jun 1 [cited 2021 Sep 28];14(2):173. Available from: /pmc/articles/PMC7250005/ Federal Ministry of Health. National Malaria Strategic Plan 2014 ‐ 2020 [Internet]. policy document. Abuja; 2017. Available from: hhttps://www.health.gov.ng/doc/NMEP-Strategic-Plan.pdf Abdullahi K, Muhammad S, Manga SB, Tunau IM. Chloroquine-resistant Plasmodium falciparum in Sokoto, North Western Nigeria. African J Biotechnol. 2003;2(8):264–8. Bosman A, Mendis KN. A Major Transition in Malaria Treatment : The Adoption and Deployment of Artemisinin-Based Combination Therapies. 2007;77(Suppl 6):193–7. Mokuolu OA, Okoro EO, Ayetoro SO, Adewara AA. Effect of artemisinin-based treatment policy on consumption pattern of antimalarials. Am J Trop Med Hyg. 2007;76(1):7–11. Goodman C, Brieger W, Unwin A, Mills A, Meek S, Greer G. Medicine sellers and malaria treatment in sub-Saharan Africa: What do they do and how can their practice be improved? Am J Trop Med Hyg [Internet]. 2007 [cited 2021 Sep 28];77(SUPPL. 6):203–18. Available from: http://www.jhsph.edu/, Brieger WR, Salako LA, Umeh RE, Agomo PU, Afolabi BM, Adeneye AK. Promoting Prepackaged Drugs for Prompt and Appropriate Treatment of Febrile Illnesses in Rural Nigerian Communities. Int Q Community Health Educ [Internet]. 2002 Aug 1 [cited 2021 Sep 28];21(1):19–40. Available from: https://journals.sagepub.com/doi/abs/10.2190/0N5X-0NVD-R0VB-4QKF?journalCode=qcha Yakasai AM, Hamza M, Dalhat MM, Bello M, Gadanya MA, Yaqub ZM, et al. Adherence to Artemisinin-Based Combination Therapy for the Treatment of Uncomplicated Malaria: A Systematic Review and Meta-Analysis. J Trop Med. 2015;2015. FMoH. National Malaria Policy 2014-2020. Fed Minist Heal Niger [Internet]. 2014;29. Available from: https://www.health.gov.ng/doc/NMEP-Strategic-Plan.pdf Talisuna AO, Adibaku S, Amojah CN, Amofah GK, Aubyn V, Dodoo A, et al. The affordable medicines facility-malaria—A success in peril. Malar J 2012 111 [Internet]. 2012 Nov 8 [cited 2021 Sep 28];11(1):1–3. Available from: https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-11-370 Edwards HM, Sarwar R, Mahmud P, Emmanuel S, Maxwell K, Tibenderana JK. The impact of the private sector co-payment mechanism (PSCM) on the private market for ACT in Nigeria: results of the 2018 cross-sectional outlet and household market surveys. Malar J [Internet]. 2022;21(1):1–17. Available from: https://doi.org/10.1186/s12936-021-04039-9 Ajayi IO, Soyannwo T, Akpa OM. Awareness and utilization of affordable medicine facility-malaria among caregivers of under-five children in Ibadan north-west local government area, oyo state. Malar Res Treat. 2013;2013. Durowade KA, Bolarinwa OA, Fenenga CJ, Akande TM. Operations and roles of patent and proprietary medicine vendors in selected rural communities in Edu Local Government Area, Kwara State, north-central Nigeria. J Community Med Prim Heal Care [Internet]. 2018 Oct 4 [cited 2022 Sep 19];30(2):75–89. Available from: https://www.ajol.info/index.php/jcmphc/article/view/178113 Hutchinson E, Droti B, Gibb D, Chishinga N, Hoskins S, Phiri S, et al. Traduire les preuves en politique dans les pays à faible revenu: Leçons tirées de la thérapie préventive au cotrimoxazole. Bull World Health Organ. 2011;89(4):312–6. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 17 Jun, 2023 Read the published version in Malaria Journal → Version 1 posted Editorial decision: Major revision 20 Jan, 2023 Reviews received at journal 12 Jan, 2023 Reviewers agreed at journal 19 Dec, 2022 Reviewers invited by journal 19 Dec, 2022 Editor assigned by journal 17 Dec, 2022 Submission checks completed at journal 17 Dec, 2022 First submitted to journal 16 Dec, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2384829","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":160857061,"identity":"30fdea35-cb6f-4811-b111-ba38736c253a","order_by":0,"name":"Olugbenga Ayodeji Mokuolu","email":"","orcid":"","institution":"Department of Paediatric, University of Ilorin","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Olugbenga","middleName":"Ayodeji","lastName":"Mokuolu","suffix":""},{"id":160857062,"identity":"f3cf7a28-faa0-44fa-bf17-6e96f8a544fa","order_by":1,"name":"Oladimeji Akeem Bolarinwa","email":"data:image/png;base64,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","orcid":"","institution":"Department of Epidemiology and Community Health, University of Ilorin","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Oladimeji","middleName":"Akeem","lastName":"Bolarinwa","suffix":""},{"id":160857063,"identity":"91ae565c-7ce0-4739-880d-df2bc5354673","order_by":2,"name":"Oluwatumobi Racheal Opadiran","email":"","orcid":"","institution":"Messentia Medicare, River Park Estate","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Oluwatumobi","middleName":"Racheal","lastName":"Opadiran","suffix":""},{"id":160857064,"identity":"10af7a7e-b01e-46e1-a5d3-b1d7542e195c","order_by":3,"name":"Hafsat Abolore Ameen","email":"","orcid":"","institution":"Department of Epidemiology and Community Health, University of Ilorin","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hafsat","middleName":"Abolore","lastName":"Ameen","suffix":""},{"id":160857065,"identity":"fd863bca-750d-4a65-bcea-4e43732d8001","order_by":4,"name":"Mehul Dhorda","email":"","orcid":"","institution":"Mahidol Oxford Tropical Medicine Research Unit, Mahidol University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mehul","middleName":"","lastName":"Dhorda","suffix":""},{"id":160857066,"identity":"dcb63830-ca9c-4b52-b36b-e40243d56f5a","order_by":5,"name":"Phaik Yeong Cheah","email":"","orcid":"","institution":"Mahidol Oxford Tropical Medicine Research Unit, Mahidol University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Phaik","middleName":"Yeong","lastName":"Cheah","suffix":""},{"id":160857067,"identity":"7bb917e3-e0c5-403a-846f-dc15546554d9","order_by":6,"name":"Chanaki Amaratunga","email":"","orcid":"","institution":"Mahidol Oxford Tropical Medicine Research Unit, Mahidol University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chanaki","middleName":"","lastName":"Amaratunga","suffix":""},{"id":160857068,"identity":"3923cbad-2e58-40cc-acc3-9e4feb7128b2","order_by":7,"name":"Freek Haan","email":"","orcid":"","institution":"Copernicus Institute of Sustainable Development, Utrecht University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Freek","middleName":"","lastName":"Haan","suffix":""},{"id":160857069,"identity":"245fb14d-cddb-4577-bf87-facdd05ec31e","order_by":8,"name":"Paulina Tindana","email":"","orcid":"","institution":"Department of Health Policy, Planning and Management, School of Public Health, College of Health Sciences, University of Ghana","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Paulina","middleName":"","lastName":"Tindana","suffix":""},{"id":160857070,"identity":"94cdc4c0-c7bd-40e7-9814-a73f1243b5a4","order_by":9,"name":"Arjen M. Dondorp","email":"","orcid":"","institution":"Mahidol Oxford Tropical Medicine Research Unit, Mahidol University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Arjen","middleName":"M.","lastName":"Dondorp","suffix":""}],"badges":[],"createdAt":"2022-12-16 09:44:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2384829/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2384829/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12936-023-04622-2","type":"published","date":"2023-06-17T21:14:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":30577277,"identity":"a7187e86-2916-463f-ad1f-7b8022cb74ff","added_by":"auto","created_at":"2022-12-20 16:05:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":41562,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-2384829/v1/970113de493a34b67a345916.png"},{"id":44731961,"identity":"e03b13ba-0d7c-4933-92bd-d064fde53273","added_by":"auto","created_at":"2023-10-16 21:48:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":632052,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2384829/v1/47a7cbb8-f49a-46d3-afdb-00ee614375e4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A framework for stakeholder engagement in the adoption of new antimalarial treatments in Africa: a case study of Nigeria","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTranslation of scientific evidence into policies and interventions is not always straightforward or swift [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. One major example is the problematic introduction of new antimalarial therapies in the late 1990s, when all conventional antimalarial monotherapies including chloroquine and sulfadoxine-pyrimethamine (SP) were failing globally due to multidrug resistance [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Expert meetings were conducted at the World Health Organization (WHO) to review evidence, culminating in policy recommendation towards the adoption of new treatment regimens in malaria endemic regions. The experience over the years, however, indicate that neither scientific evidence nor WHO recommendations were sufficient to realize effective adoption, implementation, deployment and uptake of antimalarial treatment policies [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere are numerous other drivers, often unique to individual countries, that influence the adoption of antimalarial treatment policies [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. One major driver is the impact of country-level stakeholders\u0026rsquo; engagement [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Operationalizing evidence into practice does not end with policymakers; engagement with all stakeholders (e.g regulators, suppliers, prescribers and end-users) starting from early stages of evidence generation to the final stage of uptake is central. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This manuscript is predicated on current evidence from Southeast Asia [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] regarding resistance to artemisinin and partner drugs with resultant failure of (ACTs) and the recent reports of artemisinin partial resistance from three African countries [\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Widespread artemisinin resistance in African countries could lead to a rise in the disease burden with devastating impact on mortality similar to events in the 1990s [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eArtesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) remain efficacious for treatment of uncomplicated \u003cem\u003eP. falciparum\u003c/em\u003e malaria in Nigeria and most African regions [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. There are however, reports of ACT failure reported from Burkina Faso, Angola and the Democratic Republic of Congo, which are debated [\u003cspan additionalcitationids=\"CR18 CR19 CR20\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. New classes of antimalarial therapies are being developed [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], but they are at least 5 years away from market introduction [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The WHO has recently proposed new strategies to address antimalarial drug resistance in Africa, which include better leveraging existing tools to preserve the therapeutic life of current ACTs until other viable solutions become available [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Suggestions include exploring the potential of rotating ACTs before high treatment failure rates are detected, deploying multiple first-line therapies at the same time, and extending the duration of treatment regimens [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Additionally, triple artemisinin-based combination therapies (TACTs), where artemisinin is combined with two carefully selected, widely-used partner drugs is also proposed and being investigated as a possible strategy to prevent or delay artemisinin resistance from emerging [\u003cspan additionalcitationids=\"CR25 CR26 CR27 CR28\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. All these strategies will require policy change, the context of which may be more complex depending on the type of treatment, required delivery methods, and health system variabilities among others.\u003c/p\u003e \u003cp\u003eTo aid this potential new transition, lessons learnt during previous transitions to new antimalarial drugs are discussed here. We envision they will inform future policy change to adopt new antimalarials with an emphasis on strategic stakeholder engagement and other social determinants associated with the stakeholders\u0026rsquo; mobilization. We conducted a study on the evolution and adoption of antimalarial treatment policy processes and the change of antimalarial implementation processes in Nigeria with the objective of providing perspectives that will enhance future successful uptake of important new antimalarial treatments or treatment strategies in an age of artemisinin resistance.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study is based on two approaches\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAn analysis of stakeholders\u0026rsquo; perspectives extracted from a qualitative study conducted in Nigeria between December 2019 and June 2020 involving 33 in-depth interviews (IDI) and 6 focus group discussions (FGDs) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAn analysis of programme and policy documents and two further interviews conducted in December 2021 to include historical accounts with key informants immersed in the malaria elimination program in Nigeria.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eWe adopted mixed methods involving qualitative (IDIs, key informant interviews and FGDs) data from major malaria stakeholders in Nigeria, including policy makers, regulators, manufacturers/distributors, prescribers, researchers, and end-users at community level and review of documents.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eQualitative study\u003c/h2\u003e \u003cp\u003eThe qualitative phase of the study conducted with purposively selected respondents in both the federal capital city of Nigeria, Abuja and in a North-central State, Kwara, has been described previously, [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. For this case study, we extracted information from the 33 IDIs and 6 FGDs with key stakeholders (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The study combined narrative and phenomenological strategies in qualitative enquiry.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eKey informant interviews\u003c/h2\u003e \u003cp\u003eTwo in-person interviews (~\u0026thinsp;2 hours each) were conducted with key informants immersed in the malaria elimination program in Nigeria. There were further rounds of interviews with one of the key informants for further clarification and information via phone calls. The key informants were malaria experts and researchers whose experience spanned over 25 years in malaria control in the country. The interviews were tape-recorded to secure an accurate account of the conversations and avoid data loss.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of IDIs and FGDs\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStakeholder group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRespondent interviewed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber interviewed\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIDI/FDG\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003ePolicy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNational regulatory authority officials\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIDI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eState malaria control program officials\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIDI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eRegulatory\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNAFDAC official\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIDI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNMEP private sector desk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIDI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eDistributor\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePublic sector drug wholesalers/distributors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIDI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrivate sector wholesalers/traders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIDI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eHealth service providers\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePublic sector: clinicians, pharmacists\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIDI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrivate sector: clinicians, nurses, pharmacists, drug store\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIDI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVillage health workers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFGD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMalaria Experts/Researchers\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eImmersed experts in Nigeria NMEP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eKey informant\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eEnd users\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParents / caregivers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFGD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParents/ caregivers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIDI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCommunity leaders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFGD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNAFDAC: National Agency for Food and Drug Administration and Control\u003c/p\u003e \u003cp\u003eNMEP: National Malarial Elimination Programme\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eDocument analysis\u003c/h2\u003e \u003cp\u003e To trace the evolution and adoption of antimalarial treatment policy processes and the change of implementation processes, we searched online and screened programmatic, malaria treatment guidelines and policy-papers for relevance to antimalarial policy change adoption. Boolean operators were used to narrow our search to the relevant documents from PubMed, African Journal online, Federal Ministry of Health website, WHO websites and Malaria Elimination Programme websites. The keywords used for the search were \u003cem\u003eantimalarial, policy, stakeholders\u0026rsquo; engagement\u003c/em\u003e, \u003cem\u003eartemisinin combination therapy, resistance, therapeutic efficacy\u003c/em\u003e and \u003cem\u003eNigeria.\u003c/em\u003e Of the 50 documents identified, 9 were relevant to the study and included in the analysis. The findings from the policy document review were triangulated with the thematic construct of the qualitative data to assess stakeholders\u0026rsquo; engagement in the adoption of new antimalarial treatment strategies in Nigeria.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results And Discussion","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eNigeria malaria control architecture\u003c/h2\u003e \u003cp\u003eNigeria has a population of over 200\u0026nbsp;million and the highest burden of malaria infections in Africa [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The Federal Ministry of Health (FMoH) through the National Coordinator is responsible for malaria control and elimination activities in the country [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The National Food and Drug Administration Control (NAFDAC) is responsible for regulatory function of malaria drugs and commodities. The Pharmaceuticals Manufacturing Group (PMG) plays an important role in the production of malaria commodities either independently or serving as franchise for local companies. The Nigerian health system operates a three-tier arrangement consisting of the Federal, State and Local authorities. The federal level formulates policy and controls the tertiary care. The states and local government levels are responsible for implementation of the policy. They are also responsible for regulatory, and implementation of activities related to secondary and primary levels of care respectively. Malaria service delivery, especially case management is channeled through public community and private systems. Health insurance coverage is low. Provision of antimalarials in public primary healthcare facilities is largely free or heavily subsidized while the private system is largely fee for service except few enlisted in health insurance schemes [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Doctors are the primary prescribers in the tertiary facilities and to a large extent in the secondary levels [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Various other health professionals serve as prescribers in some secondary facilities and mostly in primary health care facilities. There is also a large informal system consisting of Proprietary Patent Medicine Vendors (PPMVs) and Community Pharmacists as prescribers.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMalaria burden and treatment policy in Nigeria\u003c/h2\u003e \u003cp\u003eNigeria, with about 63\u0026nbsp;million annual cases of malaria, accounts for the largest burden of malaria globally; 26.8% and over 31.9% of the 241\u0026nbsp;million global malaria disease case and 627,000 deaths respectively [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The incidence of malaria in Nigeria reduced from 373 per thousand in 2010 to 314 in 2020 [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The prevalence from Malaria Indicator Surveys in children 2\u0026ndash;10 years has shown a decline from 42%[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] in 2010 to 23% in 2018[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. The current National Malaria Strategic Plan (NMSP 2021-25) has adopted a stratification approach to tailor actions in relation to peculiar characteristics of malaria within the various geo-political zones of the country. Since 2004, the treatment policy of malaria in Nigeria evolved from monotherapies to ACT [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Additionally, injectable artesunate for severe malaria and chemo-preventive strategies involving the use of intermittent preventive treatments in pregnancy (IPT) and seasonal malaria chemoprevention (SMC) were also adopted [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Thus, the country provides a rich experience of different cycles of translational policies on antimalarials for key lessons and adoption of best practices.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStakeholder engagement in adoption of antimalarial policy change\u003c/h2\u003e \u003cp\u003eDue to the spread of resistance to antimalarial monotherapies in the 1990s, the WHO, commissioned a review of literature in which evidence on resistance to chloroquine and other monotherapies was collected and assessed [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. These meetings resulted in the WHO recommendation to switch to ACTs as global first-line therapy for the treatment of uncomplicated falciparum malaria [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Although most endemic countries followed this recommendation and adopted ACTs in their national guidelines, significant delays were experienced between updated guidelines and the actual implementation [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIndividual countries usually appraise the recommendations of the WHO to reconsider their country-level strategies. Changing first-line therapies however involves a wide range of stakeholders at different levels of the healthcare system [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Stakeholder engagement in health policy is therefore critical for translating evidence into policy and implementation [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. An immersed expert recounted \u0026rdquo;\u003cem\u003e\u0026hellip;\u0026hellip;a major challenge in the adoption of change in monotherapy is that the scope of stakeholder engagement is often not well-defined and supported by evidence. Furthermore, tailoring the stakeholder engagement strategies based on learning or analysis of the various stakeholders\u0026rsquo; audiences are not well described.\u0026rdquo; (Interview Expert2)\u003c/em\u003e When stakeholder engagement is not well coordinated the messaging also becomes fragmented and unclear [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFrom our case scenario, we developed a framework (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) for stakeholder engagement in the introduction and deployment of new antimalarials or alternative strategies to treat malaria. This depicts the interrelations of the stakeholders ranging from those who generate evidence on antimalarial therapeutic efficacy at local and international levels down to the antimalarial end-users. The stakeholders include health policy makers, control and regulatory agencies, distributors, marketers and prescribers (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). We employ the five pillars of International Association of Public Participation (IAP2) [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e] to synthesize five stakeholder engagement spectra to guide stakeholder engagement of new antimalarials or treatment strategies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eEvolution of antimalarial policy adoption in Nigeria\u003c/b\u003e \u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003ei. Monotherapy era of pre-2001\u003c/h2\u003e \u003cp\u003ePolicy documents revealed a historical account of the evolution and adoption of antimalarial treatment policy processes in Nigeria [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. These reviews showed an evolution in treatment policies during the era of antimalarial monotherapies. Chloroquine provided relative stability in the use of monotherapy. An immersed expert recalled earliest guidance by the WHO on selection of antimalarials recommending a four-point decision scale in the programmatic deployment of antimalarials \u003cem\u003e\"...using these scales; antimalarial treatment failure rate\u0026thinsp;\u0026lt;\u0026thinsp;5% Grace, 6\u0026ndash;15%, alert, 16\u0026ndash;24% action stage which meant that there is need for identification of replacement molecule. A change was mandated when failure rate is \u0026gt;\u0026thinsp;25% and the antimalaria molecule should be replaced with another that is more efficacious.\u0026rdquo; (Interview Expert1).\u003c/em\u003e\u003c/p\u003e \u003cp\u003eIn Nigeria, efficacy of chloroquine was prolonged despite resistance reported from Southeast Asia a decade earlier [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. However, from 1988, efficacy in Nigeria declined below 70% [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Despite the reduced efficacy of chloroquine, the Nigerian Malaria Control Programme (as it was then called) waited another decade before reacting. This may be related to limited awareness of the WHO policy guidelines by national policy makers. The two experts interviewed opined that an additional factor was the popularity of chloroquine and the perceived concern about the ability of sulphadoxine-pyrimethamine (SP), which was the most viable alternative available, to withstand the same pressure as chloroquine before widespread resistance occurs. Buttressing these fears, was evidence of increasing SP resistance from East Africa where SP had earlier been adopted as the first-line therapy [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. While the country was in a dilemma, global discussion on the adoption of ACTs began. After the WHO provided evidence on drug resistance to chloroquine, Nigeria in early 2000 was tending towards adopting SP, the only available monotherapy, as their national first-line antimalarial therapy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e \u003ch2\u003eii. Transition era from monotherapy to ACT policy\u003c/h2\u003e \u003cp\u003eThe transition from monotherapy to ACT policy was not a swift process. An immersed \u003cem\u003eexpert commented \u0026ldquo;...until Nigeria engaged in the conversation of ACT adoption, the country mainly reacted to the growing evidence of treatment failure by adopting strategies to increase compliance to the existing monotherapies. Major interventions were the prepackaging of these monotherapies and the introduction of home management of malaria. Furthermore, there was an extensive interaction between WHO, NMEP, the PMG and the regulatory authorities in which consensus was reached that age-specific antimalarial drugs should become available. While the PMG went ahead to implement these changes, the need for ACT as a strategic cornerstone for the treatment of uncomplicated malaria was gaining momentum at international levels.\u0026rdquo; (Interview Expert1).\u003c/em\u003e\u003c/p\u003e \u003cp\u003eTherapeutic efficacy studies (TESs) conducted in 2002 showed that the corrected adequate clinical and parasitological response (ACPR) for chloroquine and SP in Nigeria were abysmally low at 34.7% and 57.4% respectively [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. \u003cem\u003eAn immersed expert\u003c/em\u003e recalled these worrying developments, \u003cem\u003e\u0026ldquo;\u0026hellip;The NMEP identified the next stage of the decision-making of selecting the most appropriate ACT. This was reported as the decision of another stakeholder meeting held in 2004.\u0026rdquo; (Interview Expert1).\u003c/em\u003e The communique of that meeting emphasized the prevalence of both chloroquine and SP resistance in the country, the proven efficacies of the new ACTs as reported from other countries and the need to conduct a local TES on the candidate ACTs (artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ)) to inform programmatic deployment. Hence, another TES was conducted in 2004 that indicated efficacies above 90% for both ACTs for the treatment of uncomplicated falciparum malaria [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Due to the availability of AL as a co-formulated drug and high level of tolerability, the country adopted AL as the new first-line antimalarial while ASAQ, though a co-first line was reserved as an alternative or provided only by some donors as a cheaper alternative to support care in some areas of the country [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cem\u003eAn immersed expert\u003c/em\u003e narrated \u003cem\u003e\u0026ldquo;\u0026hellip;this decision of the country, despite its intent, did not engage the PMG at any point. It was therefore regarded as a betrayal of the trust that has been built with the PMG. They complained of significant economic loss from the investments made to re-tool and re-register the newly prepackaged monotherapies. The result was that of a significant push back through intense advertisement of monotherapies by the PMG and the lack of uniformity in malaria treatment messaging. The FMoH had to set up a special committee to interphase and handle the change of management process. These issues delayed implementation of ACT use despite the relative early adoption of the ACT policies. Furthermore, several states did not include ACTs in their essential medicine lists and could therefore not invest in the ACTs. In addition, the National Health Insurance Scheme (NHIS) also continued to recommend the use of monotherapies because the capitation fees being charged was significantly related to cost of monotherapies since fever/malaria was the commonest reason for outpatient consultations\u0026rdquo; (Interview Expert1).\u003c/em\u003e\u003c/p\u003e \u003cp\u003eThe important lesson learned is that the PMG and NHIS were not adequately engaged as stakeholders in the policy change procedure, leading to inefficient deployment. The same applied for marketers and distributors who had previously invested and engaged in alternative therapies and were not compensated for these investments. There was a long delay before the prescribers had awareness of the policy change because of poor downstream communication to these stakeholder groups.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eACT policy implementation and lessons learnt\u003c/h2\u003e \u003cp\u003eFollowing the adoption phase, Nigeria rolled out implementation of ACT immediately. This was shorter than the average time-lag of 12\u0026ndash;18 months between policy adoption and implementation as reported from endemic regions [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Although Nigeria encountered some delays in evidence uptake until policy adoption (between 2001 and 2005), this was compensated for by zeal and political will to implement ACT as new treatment regimen. This was in turn reinforced by funding from the global developmental partners [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. However, there was an immediate push-back among the pharmaceutical companies who had hitherto invested heavily on age-specific pre-packaged chloroquine [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e] and those already co-formulating SP for a large demand for Eastern Africa [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe implementation strategies were also met with resistance from suppliers, distributors, prescribers, and the end-users. Multiple reasons were adduced for the initial apathy [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. The antipyretic effects of chloroquine that gave immediate relief to the patients and a sense of effectiveness to the prescribers and the suppliers created a sustained demand for chloroquine. A policy maker mentioned \u003cem\u003e\u0026ldquo;\u0026hellip;the resistance from the private sector who probably at that particular time have invested their resources to produce these monotherapy drugs and were not carried along when this policy of changing to ACT combination drugs came, they were not properly orientated.\u0026rdquo; (IDI POLREG05).\u003c/em\u003e\u003c/p\u003e \u003cp\u003eOther respondents noted that stakeholder engagement with regulatory agencies such as NAFDAC is essential for the adoption of antimalarial treatments. Failure to engage them could lead to delays in the adoption process. A policy maker mentioned \u003cem\u003e\u0026ldquo;The NAFDAC plays important role in regulation of the newly introduced antimalaria drugs in the country. So, NAFDAC is at the point of entry of any product, irrespective of which program is advancing for such products, NAFDAC need to accredit such drugs. And if that is not done, then there is every tendency that such drug will not be allowed at the program level.\u0026rdquo; (IDI POLREG02).\u003c/em\u003e\u003c/p\u003e \u003cp\u003eAnother factor was the cost of chloroquine compared to ACT. In low-income settings like Nigeria, affordability, and accessibility to ACT is crucial. The global supply and demand shortfall for ACT became an immediate burden that warranted WHO, UNICEF and other developmental partners outsourcing the procurement of ACT for the public sectors in the endemic regions, Nigeria inclusive [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Evidence from Nigeria in the early period of policy adoption and implementation revealed mixed reports on the problematic transition to ACT in Nigeria. Some end-users and prescribers interviewed cited challenges related to prescribers\u0026rsquo; distrust in ACT efficacy compared to the well-known chloroquine, while patients reported discomforting side-effects to amodiaquine.\u003c/p\u003e \u003cp\u003eThe post-adoption phase of ACT deployment in Nigeria witnessed more developmental partner support for malaria control activities, robust data generation from efficacy studies and subsequent programme evidence. The ACT case-management strengthened with backup of this evidence then became established in treatment guidelines [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. In addition, chemoprevention in pregnancy and seasonal campaigns for malaria prevention among under 5-year old children were also introduced [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. One major fall-out of the post-adoption was the monopoly of the ACT supply by the pharmaceutical industry while global efforts were compelled to patronize the monopoly. This was detrimental to the survival of the local pharmaceutical industries who had previously been major stakeholders in the policy change adoption in Nigeria. To solve this problem and to reduce the high costs of ACTs among the populations in the endemic countries, the global efforts in 2008 developed the Affordable Medicine Facility-malaria (AMFm) which was piloted in seven African countries including Nigeria [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. This policy attempted to supply ACT at a more affordable rate to the public and private systems through the principle of first line buyers who bought at a highly subsidized rate, and they were allowed a limited profit margin to make the ACTs affordable. After the pilot phase of the AMFm, the scale up was implemented under the nomenclature of Private Sector Co-payment Mechanism (PSCM). The operational model was essentially similar except that there was increasing prettification of the first line buyers in the private sector responsible for a fraction of the cost of the ACTs [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe PSCM intervention had an initial positive impact on availability of ACTs which increased significantly over the period of implementation [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. The impact was observed particularly among PPMVs with associated increased access to ACT by the poor households [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. But similar to previous subsidized public health interventions, the programmes were not sustainable [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Another limitation was that important stakeholders in the downstream of ACT policy uptake were completely neglected [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. Therefore, this evidence-based novel intervention was discontinued. Nevertheless, AMFm/PSCM still leaves a regulated supply chain for malaria in Nigeria including a stabilized ACT cost. Stakeholder groups reported that inadequate stakeholder engagement at all levels led to the poor uptake of the policy. They suggested that these should be addressed to support the adoption of future antimalarial treatments: \u003cem\u003e\u0026ldquo;To ensure that all important stakeholders are involved in such important public health intervention, we need to support it with advocacy, communication, mobilization, and sensitization. So, if we just deploy without following it up or without backing it up, we know the Behavioural Change Communication (BCC) component of our general attitude is difficult to attain.\u0026rdquo; (IDI POLREG03).\u003c/em\u003e\u003c/p\u003e \u003cp\u003eThe lesson learned was that private sector engagement was challenging since negotiated ACTs were largely available through the public sector. As with PMG, the private sector was hindered following the sudden withdrawal of both the AMFm and PSCM. There was also a mismatch in policy to diagnostically confirm each suspected case of malaria and the actual availability of diagnostic tools.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eMoving forward and recommendation\u003c/h2\u003e \u003cp\u003eFollowing the general principles, there is need for stakeholders\u0026rsquo; identification/mapping, identification of the policy issues and purpose to engage the stakeholders [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Thereafter, strategies of engagement that take into consideration the local and socio-cultural peculiarities are important for an indigenous disease like malaria. Lastly, predetermining measurable policy adoption outcomes and achievable benefits must be set.\u003c/p\u003e \u003cp\u003eFor engagement to be very effective, some respondents suggested that the content of messaging and communication regarding the rationale for a change in policy has to be well adapted to the peculiarities of the stakeholders. \u0026ldquo;\u003cem\u003eThey will be able to tell people the benefits of the [new] drugs.\u0026rdquo; (End-user FGD 01). \u0026ldquo;\u0026hellip;we give them health education about the drug, we should train the community\u0026hellip;.\u0026ldquo; (Suppl FGD 01)\u003c/em\u003e\u003c/p\u003e \u003cp\u003eA number of communication channels were recommended as effective strategies for communicating the rationale for a change in policy. Below are extracts of some of the narratives from the stakeholders;\u003c/p\u003e \u003cp\u003e \u003cem\u003e\u0026ldquo;The government should help us announce very well on the radio and when something like this is available, they should inform the king of the community. He will find a way to disseminate information either through mosque or church when the government announce on the radio. They should tell the King and he will inform the people\u0026rdquo;. (End-user FGD 05).\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003e\u0026ldquo;\u0026hellip;... in the olden times, we used the town crier\u0026hellip;. so, I think we can use the same means. Each community will decide what to do. Some use mosques, some use churches, they will make the announcement there\u0026rdquo;. (End-user FGD 05).\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003e\u0026ldquo;If you can embark on door-to-door awareness they will readily accept it\u0026rdquo;. (End-user FGD 06).\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003e\u0026ldquo;Whenever you identify the leaders within that community, there's always a particular leader in each section of the community, they will accept it\u0026rdquo;. (End-user FGD 04).\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003e\u0026ldquo;Maybe Pastors of the church, the Imam and Alfas and the schools and the clinic, the health workers they would also play a very big role to make sure that the community accepts the drugs\u0026rdquo; (IDI End-user 03).\u003c/em\u003e \u003c/p\u003e \u003cp\u003eSeveral stakeholders highlighted the importance of making training of health workers an integral part of the deployment process. They suggested that building the capacity of health workers would enable them to provide the right information about rationale for deployment of any new treatments at the community level. Policy makers suggested \u0026ldquo;\u003cem\u003ePeople should be enlightened about the drug; they should know the composition of the drug and know the side effects too so that there will be no resistance.\u0026rdquo; (IDI POLREG08). Another regulatory authority mentioned \u0026ldquo;They should train them about the new drug that is coming, the composition of the drug, we can hold a seminar or workshop to boost their capacity.\u0026rdquo; (IDI REG 08).\u003c/em\u003e These views were also shared by suppliers \u0026ldquo;\u003cem\u003eThere should be seminar for health workers, they should pay people for attending the seminar.\u0026rdquo; (Suppl FGD 02)\u003c/em\u003e\u003c/p\u003e \u003cp\u003eEngagement with end-users is required for successful adoption of any new antimalarial policy as summed up by a respondent: \u003cem\u003e\u0026ldquo;There are gatekeepers within the community; it could be traditional ruler, it could be a philanthropist within that community that is well respected and that may have contributed to the development of that environment in one way or the other, so they are key.\u0026rdquo; (IDI REG01). The perspectives of end-users suggested that there are several reasons why engagement should be an integral part of the having adequate knowledge of any new antimalarial treatment. End-users stated reasons for the engagement: \u0026ldquo;if they are informed before that if you take this drug, this is the problem, then they will not worry\u0026rdquo; (End-user FGD 01). Another end-user buttressed this: \u0026ldquo;Since we all know that initially, so definitely every drug that will be highly effective must come with side effects. So, they should tell the community this is the side effect of this drug.......\u0026rdquo; (End-user FGD 01).\u003c/em\u003e Most end-users suggested that engagement processes that seeks to address issues related to health-seeking behaviour should be adopted: \u003cem\u003e\u0026ldquo;So I think one of the strategies is to have an early engagement of the local communities, their health-seeking behaviour ultimately influences whatever you are doing, we can reduce all of those obstacles.\u0026rdquo; (End-User IDI01,). Other respondents during discussion gave insight into drug non-adherence because of lack of end-user engagement \u0026ldquo;I don\u0026rsquo;t normally complete the dosage. Once I feel much better, I stop using it.\u0026rdquo; (End-user FGD 04). \u0026ldquo;...well we have this mentality of being doctors in the house before going to the medical doctor, we treat with paracetamol and when the patient is not responding we go to the counter to get some malaria drugs like Lonart, so that is what we do primarily but if there is no response we now go to the hospital to see medical doctor.\u0026rdquo; (End-user IDI 03).\u003c/em\u003e\u003c/p\u003e \u003cp\u003ePolicy makers and regulators (e.g NAFDAC) should be engaged through adequate, convincing, and locally acceptable evidence. This will give credibility and fidelity to the new antimalarial. As narrated in the policy change era to ACT, the private sector distributors, marketers, and prescribers will play key roles if engaged earlier. Engagement of health practitioners is essential for a transition to a new antimalarial drug or treatment strategy. Several respondents anticipated challenges in private sector, where retailers and prescribers are often guided by patient demand rather than treatment guidelines. Especially in the private sector. This was considered a potential barrier to future adoption and would require active engagement of the private sector stakeholders. The same applies to a large number of informal retailers, as \u0026lsquo;over the counter\u0026rsquo; prescription without expert consultation remains common in Nigeria [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. Some suppliers mentioned that retailers and prescribers are not always aware of the magnitude of drug resistance, its causes and risks, and its implications. Therefore, providing training and information was considered important by some respondents. Such information campaigns should begin with awareness of the threat of antimalarial drug resistance and the risks involved. They should be educated on the benefit of deploying new drugs with a view to delay or prevent multidrug resistance: \u003cem\u003e\u0026ldquo;So, these are lessons learnt that moving forward, if there's anything of such a nature, and more importantly, when we are at this stage, this is the time we even need to start engaging the patient at the community.\u0026rdquo; (IDI POLREG05)\u003c/em\u003e\u003c/p\u003e \u003cp\u003eLearning from the experiences of the transition from monotherapies to ACT, \u003cem\u003eall stakeholder groups\u003c/em\u003e shared the view that implementation programs and behavior change initiatives are important to engage practitioners and patients in a prospective transition to a new therapy. The NMEP, under coordination of the Ministry of Health (MoH), was considered the most credible party to coordinate such initiatives in Nigeria. Some policy makers gave examples of models of engagement that have worked in local communities in the provision of health services that could be adopted for engagement regarding the introduction of new antimalarials: \u003cem\u003e\u0026ldquo;when we initially introduced the ACT, there's one we called role model. In deploying some of these drugs, role model has key roles to play because if you look at it, it takes a patient like 100 mins to move from his house to facility. But within a household, if we have a respected role model within the community, people will believe in him or her than the people that they, maybe, see them once in blue moon whenever they go to the hospital\u0026hellip; but these individuals\u0026hellip; we need to look at how we engage them.\u0026rdquo; (IDI POLREG08).\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eProposed framework for stakeholder engagement in adoption of new antimalarials or treatment strategies\u003c/h2\u003e \u003cp\u003eFrom the foregoing, we propose a framework for effective stakeholder engagement for future adoption of new antimalarial treatments or treatment strategies in Nigeria. The framework covers the pathway from generating evidence to making the treatments accessible and affordable to end-users. It also addresses key elements and recommendations on who to engage, the content of engagement and what strategies would support effective engagement with various key stakeholders at different levels of a transition process. The triad of evidence, policy and implementation is envisioned in a well-coordinated stakeholder spectrum with active two-way interrelationships between the stakeholders which will be informed by critically outlined strategies [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. Adopting the five pillars of IAP2, [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e] we identified a five-step approach to engage stakeholders as shown below.\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eInform\u003c/b\u003e: provide balanced and objective information on the policy change to the stakeholder in terms of the purpose, opportunities, and limitations of the policy.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eConsult\u003c/b\u003e: obtain feedback from the stakeholder on the assessment and their understanding of the policy change with the view of the local alternatives, challenges, and decisions.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eInvolve\u003c/b\u003e: work directly and together with the stakeholders to ensure that their concerns, aspirations and challenges are understood and taken into consideration.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eCollaborate\u003c/b\u003e: reiterate this is a partnership relationship with the stakeholders to take the policy change adoption decision together and to identify preferred best solutions.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eEmpower\u003c/b\u003e: place the policy adoption in the hands of the stakeholder for sustainable implementation and feedback.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eAdapting these to the Nigeria case of antimalarial policy change adoption, we identified critical stakeholders as shown in the conceptual framework (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Putting evidence at the top of policy change adoption, which should trigger the subsequent policy directions that led to the efficacy trials and change in the national antimalarial policy in the country. The policy makers must be actively engaged by the WHO and other isolated research while the policy makers in turn inform, consult, and involve other stakeholders like regulators of malarial drugs, the manufacturers, the distributors, the prescribers, and the end-users.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis paper identified that the historical evolution of antimalarial drug resistance and adopting new therapies spanned several stakeholders\u0026rsquo; engagements experiences before, during and after introduction of ACTs. Early and staged engagement of stakeholders from global bodies through regulatory authorities to end-users at the community level is critical to the successful adoption of any new treatment strategy for malaria. A framework for these engagements has been proposed as a unique contribution to enhance this process.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACPR: Adequate clinical and parasitological response\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eACT: Artemisinin-based combination therapy\u003c/p\u003e\n\u003cp\u003eAL: Artemether-lumefantrine\u003c/p\u003e\n\u003cp\u003eAMFm: Affordable Medicine Facility-malaria\u003c/p\u003e\n\u003cp\u003eASAQ: Artesunate-amodiaquine\u003c/p\u003e\n\u003cp\u003eBCC: Behavioural Change Communication\u003c/p\u003e\n\u003cp\u003eFGD: Focus Group Discussion\u003c/p\u003e\n\u003cp\u003eFMoH: Federal Ministry of Health\u003c/p\u003e\n\u003cp\u003eIAP2: International Association of Public Participation\u003c/p\u003e\n\u003cp\u003eIDI: In-depth Interview\u003c/p\u003e\n\u003cp\u003eIPT: Intermittent preventive treatment\u003c/p\u003e\n\u003cp\u003eIRB: Institutional Review Board\u003c/p\u003e\n\u003cp\u003eNAFDAC: National Agency for Food and Drug Administration and Control\u003c/p\u003e\n\u003cp\u003eNHIS: National Health Insurance Scheme\u003c/p\u003e\n\u003cp\u003eNMEP: National Malaria Elimination Programme\u003c/p\u003e\n\u003cp\u003ePMG: Pharmaceutical Manufacturing Group\u003c/p\u003e\n\u003cp\u003ePPMVs: Proprietary Patent Medicine Vendors\u003c/p\u003e\n\u003cp\u003ePSCM: Private Sector Co-payment Mechanism\u003c/p\u003e\n\u003cp\u003eSMC: Seasonal Malarial Chemoprevention\u003c/p\u003e\n\u003cp\u003eSP: Sulfadoxine-pyrimethamine\u003c/p\u003e\n\u003cp\u003eTACTs: Triple artemisinin-based combination therapies\u003c/p\u003e\n\u003cp\u003eTES: Therapeutic efficacy studies\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUNICEF: United Nation Children\u0026rsquo;s Fund\u003c/p\u003e\n\u003cp\u003eWHO: World Health Organization\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval from Institutional Review Board (IRB) was obtained from the University of Ilorin Teaching Hospital, Nigeria with approval no: \u003cem\u003eERC/PAN/2019/07/1916\u003c/em\u003e in addition to ethical approval from Oxford Tropical Medicine Research Ethics Committee (OxTREC Ref: 552-19). Prior to entering the research sites, permission to carry out the study was obtained from relevant community gate keepers, and the respondents before commencement of the interview session. Before administration of the questionnaire, the nature, purpose and process of the study were explained to the participants after which informed written consent was obtained. Necessary steps were taken to ensure confidentiality. Participants were continuously reminded of their right to withdraw from the study at any time. After each session, the participants were consulted to ensure that study findings reflected their voices and perceptions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are ethical and legal restrictions to sharing our data publicly but they are available upon request from MORU Data Access Committee (https://www.tropmedres.ac/units/moru-bangkok/bioethics-engagement/data-sharing). Most interviews are directly traceable to individual identities and therefore we cannot share the interview data without releasing the identities of the respondents. In each interview, respondents introduced themselves and spoke about their direct (working) environment. Moreover, the topics discussed and responses to questions, could be directly linked to their job positions and affiliation, especially with higher level policy and regulatory officials. We guaranteed full anonymity to the respondents prior to data collection and therefore sharing the dataset without restrictions would be unethical.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe declare that no competing interests exist.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to UK aid and the UK Government\u0026rsquo;s Foreign, Commonwealth \u0026amp; Development Office for financial support. This research was funded in whole, or in part, by the Wellcome Trust [220211]. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConceptual design and protocol development \u0026ndash;\u0026nbsp;\u003c/strong\u003eOAM, BOA, PT, CA, FdH, MD, PYC, AMD\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eField activities (Questionnaire development and validation, interviews and FGDs)-\u0026nbsp;\u003c/strong\u003eOAM, BOA, PT, FdH, ORO, HAA, CA, PYC\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData transcription and coding \u0026ndash;\u0026nbsp;\u003c/strong\u003eOAM, BOA, ORO, HAA, PT, FdH, CA, PYC\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDrafting, review and editing of Manuscript \u0026ndash;\u0026nbsp;\u003c/strong\u003eOAM, BOA, ORO, HAA, PT, FdH, CA, PYC, MD, AMD,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAcknowledgements.\u0026nbsp;\u003c/strong\u003eWe are grateful to the National Malaria Elimination Programme officers, the Regulatory Agency (NAFDAC) and all the stakeholders in Nigeria who participated in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organization. Global technical strategy for malaria 2016\u0026ndash;2030. World Heal Organ [Internet]. 2016;1\u0026ndash;35. Available from: https://apps.who.int/iris/bitstream/handle/10665/186671/9789243564999_spa.pdf?sequence=1\u003c/li\u003e\n\u003cli\u003eBosman A, Delacollette C, Olumese P, Ridley R, A R, Shretta R, et al. The use of antimalarial drugs: Report of an informal Consultation. WHO \u0026amp; Graficim. 2001. \u003c/li\u003e\n\u003cli\u003eHumphreys K, Piot P. Scientific evidence alone is not sufficient basis for health policy. Vol. 344, BMJ (Online). 2012. \u003c/li\u003e\n\u003cli\u003eWebster J, Hoyt J, Diarra S, Manda-Taylor L, Okoth G, Achan J, et al. Adoption of evidence-based global policies at the national level: Intermittent preventive treatment for malaria in pregnancy and first trimester treatment in Kenya, Malawi, Mali and the Gambia. Health Policy Plan. 2020;35(10):1364\u0026ndash;75. \u003c/li\u003e\n\u003cli\u003ede Haan F, Moors EHM, Dondorp AM, Boon WPC. Market Formation in a Global Health Transition. Environ Innov Soc Transitions. 2021 Sep 1;40:40\u0026ndash;59. \u003c/li\u003e\n\u003cli\u003eToe P, Journal M, Toe LP, Dicko B, Linga R, Barry N, et al. Operationalizing stakeholder engagement for gene drive research in malaria elimination in Africa \u0026mdash; translating guidance into practice. Malar J [Internet]. 2022;1\u0026ndash;16. Available from: https://doi.org/10.1186/s12936-022-04241-3\u003c/li\u003e\n\u003cli\u003eAdeyemo AO, Aborode AT, Bello MA, Obianuju AF, Hasan MM, Kehinde DO, et al. Malaria vaccine: The lasting solution to malaria burden in Africa. Ann Med Surg [Internet]. 2022;104031. Available from: https://doi.org/10.1016/j.amsu.2022.104031\u003c/li\u003e\n\u003cli\u003ePhyo AP, Nosten F. The Artemisinin Resistance in Southeast Asia: An Imminent Global Threat to Malaria Elimination. In: Manguin S D V, editor. Intech [Internet]. Towards Ma. London: IntechOpen; 2018. p. 15\u0026ndash;39. Available from: https://www.intechopen.com/chapters/60988 doi: 10.5772/intechopen.76519\u003c/li\u003e\n\u003cli\u003eWhite NJ. Emergence of Artemisinin-Resistant \u003cem\u003ePlasmodium falciparum\u003c/em\u003e in East Africa. N Engl J Med [Internet]. 2021 Sep 23;385(13):1231\u0026ndash;2. Available from: http://www.nejm.org/doi/10.1056/NEJMe2110659\u003c/li\u003e\n\u003cli\u003eBalikagala B, Fukuda N, Ikeda M, Katuro OT, Tachibana S-I, Yamauchi M, et al. Evidence of Artemisinin-Resistant Malaria in Africa. N Engl J Med [Internet]. 2021 Sep 23;385(13):1163\u0026ndash;71. Available from: http://www.nejm.org/doi/10.1056/NEJMoa2101746\u003c/li\u003e\n\u003cli\u003eUwimana A, Umulisa N, Zhou Z. Articles Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda : 2021;(April). \u003c/li\u003e\n\u003cli\u003eWHO. Strategy to respond to antimalarial drug resistance in Africa. WHO/UCN/GMP/202204 [Internet]. 2022;04(June). Available from: https://cdn.who.int/media/docs/default-source/malaria/who-antimalarial-drug-resistance-strategy-for-consultation.pdf?sfvrsn=9d4eaa0_6\u003c/li\u003e\n\u003cli\u003eTrape JF. The public health impact of chloroquine resistance in Africa. Am J Trop Med Hyg [Internet]. 2001 Jan 1 [cited 2022 Sep 18];64(1_suppl):12\u0026ndash;7. Available from: https://www.ajtmh.org/view/journals/tpmd/64/1_suppl/article-p12.xml\u003c/li\u003e\n\u003cli\u003eSowunmi A, Akano K, Ntadom G, Ayede AI, Ibironke FO, Aderoyeje T, et al. Therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated Plasmodium falciparum malaria -associated anaemia in Nigerian children during seven years of adoption as first-line treatments. Infect Dis Poverty [Internet]. 2017;1\u0026ndash;20. Available from: http://dx.doi.org/10.1186/s40249-016-0217-7\u003c/li\u003e\n\u003cli\u003eWHO-CDS-GMP. Artemisinin resistance and artemisinin-based combination therapy efficacy. 2018. \u003c/li\u003e\n\u003cli\u003eDorkenoo AM, Yehadji D, Agbo YM, Layibo Y, Agbeko F, Adjeloh P, et al. Therapeutic efficacy trial of artemisinin ‑ based combination therapy for the treatment of uncomplicated malaria and investigation of mutations in k13 propeller domain in Togo , 2012 \u0026ndash; 2013. Malar J. 2016;1\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eGansan\u0026eacute; A, Moriarty LF, M\u0026eacute;nard D, Yerbanga I, Ouedraogo E, Sondo P, et al. Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017\u0026ndash;2018. Malar J [Internet]. 2021 Dec 1 [cited 2022 Sep 18];20(1):1\u0026ndash;12. Available from: https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03585-6\u003c/li\u003e\n\u003cli\u003eDimbu PR, Horth R, C\u0026acirc;ndido ALM, Ferreira CM, Caquece F, Garcia LEA, et al. Continued Low Efficacy of Artemether-Lumefantrine in Angola in 2019. Antimicrob Agents Chemother [Internet]. 2021 Feb 1 [cited 2022 Sep 18];65(2). Available from: /pmc/articles/PMC7849008/\u003c/li\u003e\n\u003cli\u003eRasmussen C, Ringwald P. Is there evidence of anti-malarial multidrug resistance in Burkina Faso? Malar J [Internet]. 2021 Dec 1 [cited 2022 Sep 18];20(1):1\u0026ndash;5. Available from: https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03845-5\u003c/li\u003e\n\u003cli\u003eRasmussen C, Ringwald P. Continued Low Efficacy of Artemether-Lumefantrine in Angola? Antimicrob Agents Chemother [Internet]. 2021 Jun 1 [cited 2022 Sep 18];65(6). Available from: /pmc/articles/PMC8316127/\u003c/li\u003e\n\u003cli\u003eMoriarty LF, Nkoli PM, Likwela JL, Mulopo PM, Sompwe EM, Rika M, et al. Therapeutic Efficacy of Artemisinin-Based Combination Therapies in Democratic Republic of the Congo and Investigation of Molecular Markers of Antimalarial Resistance. Am J Trop Med Hyg [Internet]. 2021 Oct 1 [cited 2022 Sep 18];105(4):1067\u0026ndash;75. Available from: https://pubmed.ncbi.nlm.nih.gov/34491220/\u003c/li\u003e\n\u003cli\u003eTse EG, Korsik M, Todd MH. The past , present and future of anti ‑ malarial medicines. Malar J [Internet]. 2019;1\u0026ndash;21. Available from: https://doi.org/10.1186/s12936-019-2724-z\u003c/li\u003e\n\u003cli\u003eChen, I., Hsiang MS. Triple artemisinin-based combination therapies for malaria : a timely solution to counter antimalarial drug resistance. Lancet Infect Dis. 2022;3099(22 (6)):751\u0026ndash;3. \u003c/li\u003e\n\u003cli\u003evan der Pluijm RW, Amaratunga C, Dhorda M, Dondorp AM. Triple Artemisinin-Based Combination Therapies for Malaria \u0026ndash; A New Paradigm? Vol. 37, Trends in Parasitology. Elsevier Ltd; 2021. p. 15\u0026ndash;24. \u003c/li\u003e\n\u003cli\u003ede Haan F, Bolarinwa OA, Guissou R, Tou F, Tindana P, Boon WPC, et al. To what extent are the antimalarial markets in African countries ready for a transition to triple artemisinin-based combination therapies? Okell LC, editor. PLoS One [Internet]. 2021 Aug 31;16(8):e0256567. Available from: https://dx.plos.org/10.1371/journal.pone.0256567\u003c/li\u003e\n\u003cli\u003eTindana P, Guissou R, Bolarinwa OA, Tou F, Haan F De, Dhorda M, et al. PLOS ONE Ethical considerations in deploying triple artemisinin-based combination therapies for malaria : An analysis of stakeholders \u0026rsquo; perspectives in Burkina Faso and Nigeria. 2022;1\u0026ndash;15. Available from: http://dx.doi.org/10.1371/journal.pone.0273249\u003c/li\u003e\n\u003cli\u003eTindana P, de Haan F, Amaratunga C, Dhorda M, van der Pluijm RW, Dondorp AM, et al. Deploying triple artemisinin-based combination therapy (TACT) for malaria treatment in Africa: ethical and practical considerations. Vol. 20, Malaria Journal. BioMed Central Ltd; 2021. \u003c/li\u003e\n\u003cli\u003ede Haan F, Boon WPC, Amaratunga C, Dondorp AM. Expert perspectives on the introduction of Triple Artemisinin-based Combination Therapies (TACTs) in Southeast Asia: a Delphi study. BMC Public Health [Internet]. 2022 Dec 1 [cited 2022 Sep 18];22(1):1\u0026ndash;14. Available from: https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-022-13212-x\u003c/li\u003e\n\u003cli\u003evan der Pluijm RW, Tripura R, Hoglund RM, Pyae Phyo A, Lek D, ul Islam A, et al. Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial. Lancet (London, England) [Internet]. 2020 Apr 25 [cited 2022 Sep 18];395(10233):1345\u0026ndash;60. Available from: https://pubmed.ncbi.nlm.nih.gov/32171078/\u003c/li\u003e\n\u003cli\u003eTindana P, de Haan F, Mokuolu OA, Guissou R, Bolarinwa OA, Ouedraogo JB, et al. Ethical, Regulatory and Market related aspects of Deploying Triple Artemisinin-Based Combination Therapies for Malaria treatment in Africa: A study protocol. Wellcome Open Res. 2021 Apr 7;6:75. \u003c/li\u003e\n\u003cli\u003eWHO. World Malaria Report 2020: 20 years of global years and challenges. WORLD HEALTH ORGANIZATION; 2020. \u003c/li\u003e\n\u003cli\u003eFederal Ministry of Health. National Malaria Control Programme Strategic Plan 2009-2013: A Road Map for Malaria Control in Nigeria [Internet]. Abuja; 2013. Available from: https://extranet.who.int/countryplanningcycles/sites/default/files/planning_cycle_repository/nigeria/nigeria_draft_malaria_strategic_plan_2009-2013.pdf\u003c/li\u003e\n\u003cli\u003eACTwatch\u0026rsquo;Group\u0026rsquo;and\u0026rsquo;SFH. ACTwatch\u0026rsquo;Study\u0026rsquo;Reference\u0026rsquo;Document: \u0026ldquo;The\u0026rsquo;Federal\u0026rsquo;Republic\u0026rsquo;of\u0026rsquo;Nigeria\u0026rdquo; Outlet\u0026rsquo;Survey\u0026rsquo; 2015 [Internet]. Washington!DC:!PSI.; 2015. Available from: http://www.actwatch.info/sites/default/files/content/publications/attachments/Nigeria_2015 OS_Reference Document.pdf\u003c/li\u003e\n\u003cli\u003eWHO. World malaria report 2021 [Internet]. Geneva; 2021. Available from: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2021\u003c/li\u003e\n\u003cli\u003eNational Population Commission and ICF. Nigeria Demographic and Health Survey [Internet]. Abuja, Nigeria, and Rockville, Maryland, USA; 2018. 297\u0026ndash;305 p. Available from: https://dhsprogram.com/publications/publication-fr359-dhs-final-reports.cfm\u003c/li\u003e\n\u003cli\u003eWorld Bank Group. Incidence of malaria (per 1,000 population at risk) - Nigeria | Data [Internet]. SH.MLR.INCD.P3. [cited 2022 Sep 18]. Available from: https://data.worldbank.org/indicator/SH.MLR.INCD.P3?locations=NG\u003c/li\u003e\n\u003cli\u003eNational Population Commission. Federal Republic of Nigeria. Malaria Indicator Surveys in children 2-10 years [Internet]. Abuja; [cited 2022 Nov 20]. Available from: https://www.google.com/search?q=Malaria+Indicator+Surveys+in+children+2-10+years\u0026amp;client=firefox-b-d\u0026amp;biw=1585\u0026amp;bih=737\u0026amp;sxsrf=ALiCzsbJ8k8k09HIN-2cxhpd32haU9jibw%3A1668946535045\u0026amp;ei=Zxp6Y8u0ApPckgXahpCICA\u0026amp;ved=0ahUKEwiLhPuq3rz7AhUTrqQKHVoDBIEQ4dUDCA8\u0026amp;uact=5\u0026amp;oq=\u003c/li\u003e\n\u003cli\u003eFederal Ministry of Health. National Antimalarial Treatment Guidelines. 2005;(February):1\u0026ndash;29. \u003c/li\u003e\n\u003cli\u003eWHO. WHO briefing on Malaria Treatment Guidelines and artemisinin monotherapies - meeting_briefing19april.pdf [Internet]. Geneva; 2006. Available from: https://www.who.int/malaria/publications/atoz/meeting_briefing19april.pdf\u003c/li\u003e\n\u003cli\u003eBosman A, Mendis KN. A major transition in malaria treatment: The adoption and deployment of artemisinin-based combination therapies. Am J Trop Med Hyg. 2007;77(SUPPL. 6):193\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eWilliams HA, Durrheim D, Shretta R. The process of changing national malaria treatment policy: Lessons from country-level studies. Health Policy Plan. 2004;19(6):356\u0026ndash;70. \u003c/li\u003e\n\u003cli\u003eNanyunja M, Nabyonga Orem J, Kato F, Kaggwa M, Katureebe C, Saweka J. Malaria Treatment Policy Change and Implementation: The Case of Uganda. Malar Res Treat. 2011;2011:1\u0026ndash;14. \u003c/li\u003e\n\u003cli\u003eAmin AA, Zurovac D, Kangwana BB, Greenfield J, Otieno DN, Akhwale WS, et al. artemisinin-based combinations in Kenya. 2007;11:1\u0026ndash;11. \u003c/li\u003e\n\u003cli\u003eAkwanalo C, Njuguna B, Mercer T, Pastakia SD, Mwangi A, Dick J, et al. Strategies for Effective Stakeholder Engagement in Strengthening Referral Networks for Management of Hypertension Across Health Systems in Kenya. Glob Heart [Internet]. 2019 Jun 1 [cited 2021 Sep 28];14(2):173. Available from: /pmc/articles/PMC7250005/\u003c/li\u003e\n\u003cli\u003eFederal Ministry of Health. National Malaria Strategic Plan 2014 ‐ 2020 [Internet]. policy document. Abuja; 2017. Available from: hhttps://www.health.gov.ng/doc/NMEP-Strategic-Plan.pdf\u003c/li\u003e\n\u003cli\u003eAbdullahi K, Muhammad S, Manga SB, Tunau IM. Chloroquine-resistant Plasmodium falciparum in Sokoto, North Western Nigeria. African J Biotechnol. 2003;2(8):264\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eBosman A, Mendis KN. A Major Transition in Malaria Treatment : The Adoption and Deployment of Artemisinin-Based Combination Therapies. 2007;77(Suppl 6):193\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eMokuolu OA, Okoro EO, Ayetoro SO, Adewara AA. Effect of artemisinin-based treatment policy on consumption pattern of antimalarials. Am J Trop Med Hyg. 2007;76(1):7\u0026ndash;11. \u003c/li\u003e\n\u003cli\u003eGoodman C, Brieger W, Unwin A, Mills A, Meek S, Greer G. Medicine sellers and malaria treatment in sub-Saharan Africa: What do they do and how can their practice be improved? Am J Trop Med Hyg [Internet]. 2007 [cited 2021 Sep 28];77(SUPPL. 6):203\u0026ndash;18. Available from: http://www.jhsph.edu/,\u003c/li\u003e\n\u003cli\u003eBrieger WR, Salako LA, Umeh RE, Agomo PU, Afolabi BM, Adeneye AK. Promoting Prepackaged Drugs for Prompt and Appropriate Treatment of Febrile Illnesses in Rural Nigerian Communities. Int Q Community Health Educ [Internet]. 2002 Aug 1 [cited 2021 Sep 28];21(1):19\u0026ndash;40. Available from: https://journals.sagepub.com/doi/abs/10.2190/0N5X-0NVD-R0VB-4QKF?journalCode=qcha\u003c/li\u003e\n\u003cli\u003eYakasai AM, Hamza M, Dalhat MM, Bello M, Gadanya MA, Yaqub ZM, et al. Adherence to Artemisinin-Based Combination Therapy for the Treatment of Uncomplicated Malaria: A Systematic Review and Meta-Analysis. J Trop Med. 2015;2015. \u003c/li\u003e\n\u003cli\u003eFMoH. National Malaria Policy 2014-2020. Fed Minist Heal Niger [Internet]. 2014;29. Available from: https://www.health.gov.ng/doc/NMEP-Strategic-Plan.pdf\u003c/li\u003e\n\u003cli\u003eTalisuna AO, Adibaku S, Amojah CN, Amofah GK, Aubyn V, Dodoo A, et al. The affordable medicines facility-malaria\u0026mdash;A success in peril. Malar J 2012 111 [Internet]. 2012 Nov 8 [cited 2021 Sep 28];11(1):1\u0026ndash;3. Available from: https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-11-370\u003c/li\u003e\n\u003cli\u003eEdwards HM, Sarwar R, Mahmud P, Emmanuel S, Maxwell K, Tibenderana JK. The impact of the private sector co-payment mechanism (PSCM) on the private market for ACT in Nigeria: results of the 2018 cross-sectional outlet and household market surveys. Malar J [Internet]. 2022;21(1):1\u0026ndash;17. Available from: https://doi.org/10.1186/s12936-021-04039-9\u003c/li\u003e\n\u003cli\u003eAjayi IO, Soyannwo T, Akpa OM. Awareness and utilization of affordable medicine facility-malaria among caregivers of under-five children in Ibadan north-west local government area, oyo state. Malar Res Treat. 2013;2013. \u003c/li\u003e\n\u003cli\u003eDurowade KA, Bolarinwa OA, Fenenga CJ, Akande TM. Operations and roles of patent and proprietary medicine vendors in selected rural communities in Edu Local Government Area, Kwara State, north-central Nigeria. J Community Med Prim Heal Care [Internet]. 2018 Oct 4 [cited 2022 Sep 19];30(2):75\u0026ndash;89. Available from: https://www.ajol.info/index.php/jcmphc/article/view/178113\u003c/li\u003e\n\u003cli\u003eHutchinson E, Droti B, Gibb D, Chishinga N, Hoskins S, Phiri S, et al. Traduire les preuves en politique dans les pays \u0026agrave; faible revenu: Le\u0026ccedil;ons tir\u0026eacute;es de la th\u0026eacute;rapie pr\u0026eacute;ventive au cotrimoxazole. Bull World Health Organ. 2011;89(4):312\u0026ndash;6. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"malaria-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"malj","sideBox":"Learn more about [Malaria Journal](http://malariajournal.biomedcentral.com/)","snPcode":"12936","submissionUrl":"https://submission.nature.com/new-submission/12936/3","title":"Malaria Journal","twitterHandle":"@malariajournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"artemisinin resistance, stakeholder engagement, artemisinin-based combination therapy, framework, antimalarial treatment policy","lastPublishedDoi":"10.21203/rs.3.rs-2384829/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2384829/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eRecent reports of artemisinin partial resistance from Rwanda and Uganda are worrisome and suggest a future policy change to adopt new antimalarials. We conducted a case study on the evolution, adoption, and implementation of new antimalarial treatment policies in Nigeria. The main objective is providing perspectives to enhance the future uptake of new antimalarials, with an emphasis on stakeholder engagement strategies.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis case study is based on an analysis of policy documents and stakeholders\u0026rsquo; perspectives drawn from an empirical study conducted in Nigeria, 2019\u0026ndash;2020. A mixed methods approach was adopted, including historical accounts, review of programme and policy documents, and qualitative in-depth interviews and focus group discussions. Themes for the framework were developed and applied to the case study.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e Based on policy documents reviewed, the adoption of artemisinin-based combination therapies (ACTs) in Nigeria was swift due to political will, funding and support from global developmental partners. However, implementation of ACTs was met with resistance from suppliers, distributors, prescribers, and end-users, attributed to market dynamics, costs and inadequate stakeholder engagement. Deployment of ACTs in Nigeria witnessed more developmental partner support, robust data generation, ACT case-management strengthening and evidence on antimalarial use in severe malaria and antenatal care management. We propose a framework for effective stakeholder engagement for future adoption of new antimalarials or antimalarial treatment strategies. The framework covers the pathway from generating evidence to making treatment accessible and affordable to end-users. It addresses who to engage with, the content of engagement and what strategies would support effective engagement with key stakeholders at different levels of the transition process.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eEarly and staged engagement of stakeholders from global bodies through regulatory authorities to end-users at the community level is critical to the successful adoption and uptake of new antimalarial treatment policies. A framework for these engagements has been proposed as a unique contribution to enhancing this process.\u003c/p\u003e","manuscriptTitle":"A framework for stakeholder engagement in the adoption of new antimalarial treatments in Africa: a case study of Nigeria","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-12-20 16:05:42","doi":"10.21203/rs.3.rs-2384829/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-01-20T15:20:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-01-12T13:34:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"e64acd15-00e9-4bfe-af79-08eed880f4e3","date":"2022-12-19T17:19:44+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-12-19T17:09:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-12-17T10:48:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-12-17T10:48:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"Malaria Journal","date":"2022-12-16T09:32:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"malaria-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"malj","sideBox":"Learn more about [Malaria Journal](http://malariajournal.biomedcentral.com/)","snPcode":"12936","submissionUrl":"https://submission.nature.com/new-submission/12936/3","title":"Malaria Journal","twitterHandle":"@malariajournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"55ad4458-4f1f-4583-9172-60cffa7761e2","owner":[],"postedDate":"December 20th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T21:32:43+00:00","versionOfRecord":{"articleIdentity":"rs-2384829","link":"https://doi.org/10.1186/s12936-023-04622-2","journal":{"identity":"malaria-journal","isVorOnly":false,"title":"Malaria Journal"},"publishedOn":"2023-06-17 21:14:10","publishedOnDateReadable":"June 17th, 2023"},"versionCreatedAt":"2022-12-20 16:05:42","video":"","vorDoi":"10.1186/s12936-023-04622-2","vorDoiUrl":"https://doi.org/10.1186/s12936-023-04622-2","workflowStages":[]},"version":"v1","identity":"rs-2384829","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2384829","identity":"rs-2384829","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}