Journal of Mosquito Research, 2024, Vol.14, No.5, 264-275 http://emtoscipublisher.com/index.php/jmr 267 concerns related to adverse reactions, and issues with achieving sufficient population coverage. These challenges impact the overall efficacy of vaccination programs, especially in endemic regions of Africa and South America. 3.1 Vaccine shortages and distribution issues Vaccine shortages have been a recurring issue in yellow fever control, often exacerbated during large-scale outbreaks. A notable example is the 2016 yellow fever outbreak in Angola and the Democratic Republic of Congo, where a global shortage of the 17D-204 yellow fever vaccine necessitated the use of fractional dosing strategies. This involved administering smaller doses to stretch limited supplies, which, although effective, raised concerns about the duration of immunity provided by these doses (Nnaji et al., 2019). Fractional dosing was used in a preemptive campaign in Kinshasa, resulting in high rates of seroconversion, suggesting that this approach could be a viable stop-gap solution during supply crises (Ahuka-Mundeke et al., 2018). The shortage issue is often compounded by manufacturing difficulties, as the production of the yellow fever vaccine relies on specialized egg-based technology, which limits the rapid scale-up of production. During the 2017 shortage in the United States, the importation of STAMARIL® under an expanded access investigational new drug protocol provided an alternative, but this solution required coordinated efforts between regulatory bodies and limited distribution sites (Gershman et al., 2017). The reliance on a single manufacturer for vaccine production further exacerbates supply vulnerabilities, emphasizing the need for diversified manufacturing sources and investments in new vaccine production technologies, such as cell culture-based methods. 3.2 Adverse reactions and safety concerns While the 17D yellow fever vaccine is highly effective, its administration is not without risks. Serious Adverse Events (SAEs), although rare, have been a significant concern, especially in certain populations. Yellow Fever Vaccine-Associated Viscerotropic Disease (YEL-AVD) and yellow fever vaccine-associated neurotropic disease (YEL-AND) are two of the most severe reactions that can occur post-vaccination, characterized by multi-organ failure and neurological complications, respectively (Rojas et al., 2023). These reactions tend to be more common in individuals over the age of 60 and those with compromised immune systems, such as those receiving immunosuppressive therapy or with underlying autoimmune conditions (Croce et al., 2017). Safety surveillance during emergency vaccine importation programs, such as the introduction of STAMARIL® in the United States, has been crucial for monitoring these risks. A study of STAMARIL® administration during the U.S. vaccine shortage found a very low incidence of SAEs, consistent with previous safety profiles of the vaccine, with reported adverse events mainly including mild reactions such as fever and localized pain at the injection site (Rojas et al., 2023). Despite these low rates, the potential for severe reactions necessitates a careful risk-benefit analysis for vaccination, especially in non-endemic regions where the risk of exposure is lower. Efforts are ongoing to develop safer alternatives, such as inactivated or recombinant yellow fever vaccines, which could reduce the risk of these severe adverse reactions. However, these alternatives are still in experimental stages and have not yet replaced the widespread use of the 17D vaccine in routine immunization programs. 3.3 Population coverage and immunization gaps Achieving adequate immunization coverage is critical for controlling yellow fever outbreaks, yet many endemic regions face significant immunization gaps. These gaps are often due to logistical challenges, such as difficult-to-reach populations, inadequate healthcare infrastructure, and fluctuating political stability, which can hinder vaccination campaigns. A systematic review highlighted that mass vaccination campaigns have been effective in increasing coverage in some regions, but coverage often falls short of the levels needed to achieve herd immunity, particularly in rural and isolated areas (Jean et al., 2020). Immunization gaps are further exacerbated by vaccine hesitancy and misinformation, which can reduce community acceptance of vaccination programs. For example, misinformation about vaccine safety has been shown to decrease uptake, even in areas where the risk of yellow fever transmission is high. Addressing these challenges requires targeted communication strategies and community engagement to build trust in the vaccination process and address concerns about vaccine safety.
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