Date Published: August 15, 2019
Publisher: Public Library of Science
Author(s): Sarah M. Beargie, Colleen R. Higgins, Daniel R. Evans, Sarah K. Laing, Daniel Erim, Sachiko Ozawa, Luzia Helena Carvalho.
Substandard and falsified medications pose significant risks to global health. Nearly one in five antimalarials circulating in low- and middle-income countries are substandard or falsified. We assessed the health and economic impact of substandard and falsified antimalarials on children under five in Nigeria, where malaria is endemic and poor-quality medications are commonplace.
We developed a dynamic agent-based SAFARI (Substandard and Falsified Antimalarial Research Impact) model to capture the impact of antimalarial use in Nigeria. The model simulated children with background characteristics, malaria infections, patient care-seeking, disease progression, treatment outcomes, and incurred costs. Using scenario analyses, we simulated the impact of substandard and falsified medicines, antimalarial resistance, as well as possible interventions to improve the quality of treatment, reduce stock-outs, and educate caregivers about antimalarial quality.
We estimated that poor quality antimalarials are responsible for 12,300 deaths and $892 million ($890-$893 million) in costs annually in Nigeria. If antimalarial resistance develops, we simulated that current costs of malaria could increase by $839 million (11% increase, $837-$841 million). The northern regions of Nigeria have a greater burden as compared to the southern regions, with 9,700 deaths and $698 million ($697-$700 million) in total economic losses annually due to substandard and falsified antimalarials. Furthermore, our scenario analyses demonstrated that possible interventions—such as removing stock-outs in all facilities ($1.11 billion), having only ACTs available for treatment ($594 million), and 20% more patients seeking care ($469 million)—can save hundreds of millions in costs annually in Nigeria.
The results highlight the significant health and economic burden of poor quality antimalarials in Nigeria, and the impact of potential interventions to counter them. In order to reduce the burden of malaria and prevent antimalarials from developing resistance, policymakers and donors must understand the problem and implement interventions to reduce the impact of ineffective and harmful antimalarials.
Malaria is endemic in Nigeria where the entire country’s 191 million residents are at risk [1, 2]. Plasmodium falciparum causes an estimated 99.7% of deaths due to malaria with a disproportionate number of deaths in children under five [1, 3]. In 2017, Nigeria had an estimated 53.7 million cases of malaria across all ages, which accounted for 25% of all clinical episodes of malaria worldwide . Furthermore, 19% of the global estimate of malaria deaths (81,600 deaths in 2017) occurred in Nigeria, making Nigeria the single most malaria-burdened country in the world [1, 4].
The SAFARI (Substandard and Falsified Antimalarial Research Impact) model is an agent-based model used to estimate the health and economic impact of substandard and falsified antimalarials on children under five [14, 15]. The methods for the development of the SAFARI model are described in detail in other publications [14, 15], with adaptations specific to Nigeria outlined here. The SAFARI model was built in Python to simulate population characteristics, malaria infection, patient care-seeking, disease progression, treatment outcomes, and associated costs of malaria. Agent-based models capture greater heterogeneity in the flow and actions of agents by incorporating individual characteristics, as opposed to a Markov model or a decision tree that assume population groups are homogenous. Heterogeneity is incorporated into the model through characteristics ascribed to each of the 25,000 simulated child agents, including demographic characteristics, individual incidence, and care-seeking probabilities. These characteristics drive the actions of agents and allow for a more granular analysis of the results. Four demographic characteristics—geographic region, rural/urban, wealth quintile, and level of maternal education—were applied to each child in the model, according to the distributions from the most recent (2015) Nigeria Malaria Indicator Survey (MIS) . We also adjusted for regional variations in malaria transmission in Nigeria, with higher transmission in the northern region as compared to the southern region. This was incorporated through each agent’s individual probability of becoming ill with malaria, reflecting the prevalence of malaria by region.
Annually, we simulated approximately 24 million cases of malaria in children under five in Nigeria. Of cases that progressed to severe, we estimated 147,000 hospitalizations, 8,200 cases of neurological sequelae, and 78,000 deaths per year. The total economic impact of malaria in Nigeria was estimated at $7.76 billion (7.73–7.80 billion) with $7.36 billion (95% of total economic impact, 7.33–7.40 billion) in productivity losses, including $4.1 billion in lifetime productivity losses and $3.08 billion in short-term productivity losses. Direct costs of seeking medical treatment for malaria were approximately $401 million (5% of total economic impact, 400.4–401.4 million), which included $316 million for consultation costs, $59.3 million for medication costs, $9.5 million for transportation costs, $8.97 million for hospitalization costs, and $7.5 million for testing costs. Up to 33% of the direct costs of malaria treatment ($134 million) were paid out-of-pocket, whereas the health facility incurred the remainder of the costs ($267 million). The health and economic burden of malaria in Nigeria is summarized in Table 2.
The results demonstrate the threat posed by substandard and falsified antimalarials and the importance of improving access to good quality malaria treatment in Nigeria. Substandard and falsified antimalarials were estimated to be responsible for $892 million ($890–893 million) in costs annually in Nigeria, and was attributable for 6%-23% of the health and economic burden of malaria in the country. If artemisinin resistance were to develop to reduce the effectiveness of ACTs, we simulated that current economic costs could increase by 11% annually ($839 million), including growth in direct costs by 11% ($44.6 million). Improving the quality of antimalarials would make a significant impact in reducing the burden of malaria in Nigeria.