Health Outcome of Quadrivalent and Trivalent Influenza Vaccines


The health problem considered in this paper is the epidemic of influenza, a small enveloped virus that is highly contagious. To date, the continuous circulation of influenza viruses and the emergence of reassortant strains of animal origin pose a constant danger to the health of the population of all countries. Clinical implications of influenza are associated with the involvement of lung tissue and pleura (Arefin et al., 2019). It is possible to develop respiratory distress syndrome, in which patients need hospitalization and transfer to artificial lung ventilation within a day from the onset of symptoms. The economic implications of an influenza pandemic require high annual costs, resulting in a decline in GDP. For some countries in South Asia and Africa, the decline in GDP as a result of the medical costs associated with influenza is equal to the level of the average economic growth rate of these States.

Treatments to be analyzed in this review are annual vaccinations that protect against three or four of the most common strains of the virus in a given area. The study will involve influenza vaccines of different compositions. These are four-component, three-component, and two-component vaccines that include an appropriate number of virus strains (de Boer et al., 2018).

The reason for performing this paper is to evaluate the cost-effectiveness of influenza vaccination, as well as the existing limitations. The purpose of the work is to determine the economic effect of both medical expenses and indirect costs.

The various efforts performed by different countries in preparing and developing strategies to curb the Influenza pandemic have been prioritized. However, Influenza vaccines are hardly utilized in low and middle-income nations. The assessment of whether Quadrivalent influenza vaccines are better than trivalent influenza vaccines has been done by evaluating the cost-effectiveness of the Quadrivalent Influenza vaccine (QIV) and Trivalent Influenza vaccine (TIV). The literature assessment systematically evaluates the evidence of the economic burden initiated by influenza in low and middle-income countries and shows the financial consequences of influenza disease in the countries (Arefin et al., 2019). It also examines the reasons for the limited use of influenza vaccines and the vaccination costs in lower and middle-class countries.

Still, it illustrates how the safety and availability of supply issues affect health results in regions that are more vulnerable to the disease. In addition, it provides different articles that cover numerous subjects on the disorders and can help conduct research.


The inclusion and exclusion criteria selected for this paper are aimed at fully reflecting the new economic realities and health needs and are based on the PICO question. The exclusion criterion among patients was the absence of a flu shot. Inclusion criteria consisted of the presence of complete influenza vaccination in patients. In addition, the study involved people with pulmonary complications after influenza — pneumonia or bronchitis, cardiovascular problems, and disorders of the nervous system.

The interventions selected for the study consist in monitoring epidemiological data on the prevalence of the disease (disease burden) prior to vaccination. An intervention was also performed to determine the immunogenicity of the vaccines intended for use and to monitor the effectiveness of vaccination. The comparator will be conducted on the basis of comparing the costs of vaccinations and treatment, payment of sick leave, and other manipulations with influenza patients. Monetary indicators of investments in vaccinations and the treatment of patients will be compared. For comparison reasons, all cost currencies would be converted to dollars for 2020. The chosen dollar exchange rate in relation to other world currencies will allow you to get an up-to-date picture of the economic effectiveness of influenza vaccination. Two outcomes from vaccination will be considered: both cases of influenza and their absence. A disease transferred after vaccination in a mild form without complications will be regarded as a positive outcome (Wiley, 2018). Among the economic outcomes, which consist of the level of costs per influenza patient, both high and low indicators will be included.

The study will include works in different languages, translated into English, in order to collect the most objective picture of economic efficiency. Geographic areas include both developed and developing countries with both low and high levels of vaccination of the population and the incidence of influenza. However, the largest number of studies will affect the situation in large regions of Asia, Europe, Africa, and North America (Neuzil et al., 2017). This is due to the small number of works on this topic concerning geographical areas of a smaller area. Another important inclusion criterion will be the time period associated with the start of multicomponent influenza vaccination. In addition, the time frame will be applied relatively to flu cases: patients with symptoms from 2 to 7 days. Patients less than a week after vaccination will be excluded from the group of vaccinated people.

The created search strategy was to accumulate, encode and process economic and clinical data on vaccination and influenza incidence. The strategy of analytical information processing included the comparison and synthesis of the obtained data. In the course of the research, ten authoritative scientific sources were used, including the works of African, French, and American researchers (de Boer et al., 2018); electronic databases were taken from the official WHO website. The data presented in this paper are obtained from reputable journals known in the medical community. During the use of the PRISMA Flow diagram, 5 of the 15 works selected initially were excluded. The reasons why the report’s data were excluded are related to the presence of false or distorted information in them that does not correspond to official WHO statistics.

Influenza Transmission and Health Impacts

Influenza spreads quickly to patients and medical services faculty in medical care settings after acquiring guests, staff, or patients. For patients with immune-compromised systems, an Influenza upsurge can lead to crippling consequences. Visitors and health care workers with asymptomatic or gentle flu sickness are susceptible to influenza infections. The amount of virus that induces an infection depends on the size of infectious particles administered. The virus plays a risky role in damaging the respiratory system and causing infection in both the lower and upper airways (Arefin et al., 2019). The transmission can either be airborne, contact, or droplet transmission.

Transmission through contact can involve body-to-body surface contact, which is known as direct transmission, or it can happen when one touches contaminated surfaces or objects such as hands, countertops, and needles. The transmission from touching contaminated surfaces is known as indirect contact (de Boer et al., 2018). The transmission of droplets happens when the sick host produces transmittable droplets either by sneezing or coughing. According to de Boer et al. (2018), these droplets are large. When they contact another person’s nasal mucosa, mouth, and conjunctiva, the person ends up contracting the illness. In airborne transmission, the produced infectious droplets remain in the air and are distributed in a closed room or facility by the air currents (de Boer et al., 2018). When inhaled by a vulnerable person with low immunity, the host is infected, leading to death or severe adverse effects. The overall health impact includes death, hospitalizations, and severe infections, which vary with seasons. To prevent severe seasonal influenza illness, low and middle-income countries need to invest in surveillance systems that will help them monitor the infections. However, introducing the Quadrivalent influenza vaccine has made the policymakers think about replacing the Trivalent influenza vaccines.

Age Group Vaccination Reviews

All age groups, children, adults, and the elderly, are infected by the influenza virus. However, the elderly are more susceptible to the risks associated with influenza disease; thus, influenza vaccination is highly advocated for them. However, the injection has been suggested for guardians and health workers since they often contact the infections. People of all ages with other medical conditions are in more danger of flu-related entanglements than the rest of the population (de Francisco (Shapovalova) et al., 2015). TIV is the recommended vaccine used in individuals with high risk. The use of high TIV doses has been proved to be effective and safe with no adverse effects. These vaccines, both the QIVs and TIVs, are considered safe for children and adults.

Children are susceptible to influenza infections; thus, a recommendation of influenza vaccination was implemented targeting an age group of 7 to 24 months. (Neuzil et al., 2017). For children above six months, TIVs are the recommended and authorized injections (Wiley, 2018). However, QIV has been observed to contain the Yamagata and Victoria lineages of the B virus, which shows a more outstanding antibody defense against the immunogenicity and additional B strain than TVs (Ortiz & Neuzil, 2019). However, the health systems in low and middle-income countries lack proper structures for healthcare to administer and disseminate these vaccinations.

Economic Burden

The scope of the burden of influenza varies with age and the health of the patient. For instance, in an investigation in South Africa, which is renowned for possessing the most extensive human immunodeficiency infection (HIV) pervasiveness, it was assessed that individuals who are HIV positive are at higher risk of contracting influenza-associated lower respiratory infections compared to HIV-uninfected people (Hendriks et al., 2018). Hendriks et al. (2018) suggest that HIV-infected people have a risk 4-8 of contracting the flu compared to HIV uninfected. The differences between financial constraints, socio-economic factors, health care financial plans, and the formulated budgetary plans do not allow the Cost-effectiveness outcomes to have the same effects between different countries (Wiley, 2018). The complications related to influenza disease are higher in children and the elderly.

Those living in closed communities such as Refugee camps, small settlements, and plantations are more susceptible to these infections because proximity increases transmission rates. The economic factor is estimated by the assessment of the sickness funds (Hendriks et al., 2018. Seasonal Influenza immunization continues to pose a crisis in the U.S due to factors such as inadequate immunization vaccines (Wiley, 2018). The cost-efficiency of Influenza vaccination varies between states due to the difference in influenza epidemiology, HIV prevalence, and unit cost (de Boer et al., 2018). The author suggests that to assess whether Quadrivalent Influenza Vaccines are better and more cost-efficient than Trivalent Influenza vaccines depends on the budgetary impact, countries’ willingness to pay the threshold and influenza’s burden on the said country.

People with specific underlying health conditions comprise the elderly and young, who are considered to be at higher risk of developing multifaceted complications. In addition, influenza poses a critical financial weight that is accrued from medical productivity losses and costs. In low-and middle-income nations, expenditures stemming from influenza may have a huge financial impact that has been surveyed at 3–7% of (GDP) per capita, diverged from simply 0.05–0.14% of GDP per capita in revenue generation of the nations (Hendriks et al., 2018). The previously done economic analysis on influenza immunization had focused on high-income countries overlooking the monetary effects of influenza vaccination in Low and middle-revenue nations. The economic burden of the infection covers the instant expenses to the health services, people and the unintended budgets felt in the output losses, which affect the broader economy. The direct costs in middle and low-income countries Compared to high-income economies are lower and productivity losses higher. Thus, due to different socio-economic factors, co-morbidities, budget impacts, infrastructure, and health care plans, the economic cost value of the Trivalent influenza vaccines and Quadrivalent influenza vaccines vary.

Reasons for Limited Use of Influenza Vaccines

WHO’s routine immunization services do not reach the Low and middle-income countries due to poor infrastructure to reach the people in these communities and administer the immunizations. The systems used to evaluate, assess, regulate and administer these vaccines are weak thus cannot support the set immunization program for adults and children (Ortiz & Neuzil, 2019). Neuzil et al. (2017) say that the lack of clarity on the importance of prioritizing the immunization, limited data on the economic burden it poses, and the limited data on the vaccine’s efficacy has led to its underused in these low and middle-income countries. To increase the efficiency of the vaccine being administered, it is vital to understand the epidemiology of this disease is crucial (Gupta et al., 2012). According to Ortiz & Neuzil (2019), effective surveillance needs to be put in place to establish the disease burden and overall risk in the targeted groups such as children, older people, and pregnant women.

The already available national data showing the stain, disease burden, and timing can effectively help reduce the constraints that have made Some Low and middle-income countries prefer to administer the periodic Influenza vaccine in their vaccination package. They are also considering whether this program should involve Trivalent Influenza vaccines or Quadrivalent Influenza vaccines (de Boer et al., 2017). However, identifying target populations, patients with chronic conditions, and the effective vaccination strategies that will target specific endangered clusters of individuals in the low and Middle-Income countries can be challenging. For the Low and middle-income countries to consider the practice of the influenza vaccines, data on health outcomes, such as severe illness and mortality, are needed. The lack of a sound vaccination dissemination system that regularly monitors the infections, the poor infrastructure, and the financial constraints also cause the limited use of influenza vaccines.


The cost-effectiveness of QIV fluctuates among different countries because of differences in the study of disease transmission, co-morbidities, and unit costs. The burden of influenza B decides the success of QIV or TIV among the targeted population and the country’s willingness to undergo the strains associated with the immunization depending on the budget (de Boer et al., 2018). De Boer et al. (2018), using an energetic modeling study authorized by the world health organization, recommends that QIV may be more financially savvy than TIV in the specified countries under certain conditions.

Quadrivalent Influenza vaccines provide a better health benefit, according to Hendriks et al. (2018). If high attack rates were assumed, QIV would be cost-effective (de Boer et al., 2018). Substituting QIV for TIV would mean an extra expense of 25–29% spending increment for occasional flu, resulting in an increase in the annual cost of immunization, leading to a rise in the National budget (Neuzil et al., 2017). The high costs associated with Quadrivalent Influenza vaccines might lead low and middle-income countries to select the Trivalent Influenza vaccines due to the low immunization costs. Low-income countries will prioritize the affordability of the vaccines, not their effectiveness (Ortiz & Neuzil, 2019). The QIV prices are significantly more than the prices of Trivalent Influenza vaccines (Hendriks et al., 2018). When the TIV doses are increased, the health gain is close to that associated with QIV; therefore, these low and middle-income countries choose to stick to the Trivalent Influenza vaccines as a better and cost-reducing option.

However, these countries need to decide if the health gain out-gauges the extra cost accrued from the utilization of QIV. Inoculating a bigger group of people with TIV has superior cash esteem regarding the effects on the wellbeing outcome. Still, QIV leads to a significant decrease in influenza prevalence, hospitalizations, and death (Hendriks et al., 2018). The production of seasonal Trivalent Influenza vaccines routinely uses a lot of time. Effectively finishing each vaccine production yearly, the vaccination process involves ideal and consistent correspondence between the WHO, manufacturers, and administrative units. Still, the introduction of QIV adds additional production risks and market delays (Newall et al., 2017). Newall et al. (2017) discovered that immunization programs considered economically efficient are not implemented in developing countries. The cost-effective intervention is not always prioritized for financial backing due to insufficient financial resources (Newall et al., 2017). Decision-makers in these countries might prioritize other inoculation programs for the same budget increment, keep a level immunization financial plan, and opt for the cheap TIV instead of acquiring costly QIV influenza vaccinations.

Safety and Supply Issues

The routine seasonal production of Trivalent Influenza vaccines takes a considerable amount of time. To effectively finish each progression in the flu immunization producing cycle, timely and regular correspondence between the WHO, manufacturer, and administrative authority has required the introduction Of Quadrivalent Influenza vaccines would mean additional market delays and production risks (Newall et al., 2017). Vaccine creation begins one year before the set date of the agreement in the Northern and Southern hemispheres (Hendriks et al., 2018). The vaccine production steps are time-critical and require an exceptional manufacturing environment. Thus, replacing the trivalent Influenza vaccines in the market comes with production risks and untimely market delays. This change could pose a lot of practical difficulties in the market. Safety policies of influenza vaccines need to be well understood to reduce the adverse effect of a reaction (Wiley, 2018). The vaccine’s safety is highly critical in creating public confidence in the vaccination programs. The flu shots are advocated for children, adults with other medical issues, and older persons who are highly susceptible to infections. These vaccines are required to meet the required health standards and guidelines since they are provided to healthy individuals such as children.

World health organization monitors these vaccines before they are issued. The management on the economic assessment of influenza vaccination, set up by WHO, defines heretical concepts and the best methodological practices that facilitate efficient guidance on influenza vaccination evaluation in Low and middle-income nations (Wiley, 2018). This guideline includes an economic assessment of the Influenza vaccine in terms of the estimates of adverse events that may occur after immunization (Hendriks et al., 2018). In low-income areas, trivalent influenza vaccines are better since they are affordable, practical, and logistically feasible (Hendriks et al., 2018). During clinical trials, the recognition of potentially severe adverse reactions should be considered. These potential risks can cause drastic deviations in the invention course, specifically if the responses are deadly and put lives at risk (Wiley, 2018). The safety of these vaccines is crucial because it’s administered to many healthy persons; thus, the WHO should ensure the manufactured vaccines meet the required standards. The decision to replace the Trivalent Influenza vaccines with QIV depends on the transition on the country’s burden and the resources available for the transitions in the manufacturing process.

Health Effects and Clinical Outcome

Influenza causes premature death, and individuals who are HIV positive have a higher mortality rate if infected by influenza than the Non-HIV infected individuals (Arefin et al., 2019). Vaccination reduces clinical visits, hospitalizations, and mortality rates. According to the research done byNeuzil et al. (2017) and de Boer et al. (2017), the advantage of TIV over QIV was assessed to be a 13.1% decrease of suggestive flu and an 18.0% decrease of flu-associated death. Introducing Quadrivalent Influenza vaccines would reduce influenza cases; lessen outpatient visits, hospitalizations, and death. In Agincourt SA, when the QIV vaccine was used over TIV, the outcomes gave an estimation of a 13.1% decrease of suggestive flu and an 18.0% decrease of flu-related mortality (Arefin et al., 2019). From the data collected in the two influenza seasons by Gupta et al. (2012), those vaccinated with QIV, 21364 of 53627 (5.3%) and 6365 of 133147 (6.5%) were hospitalized distinguished to 7873 of 111297 (8.4%) and 4423 of 43222 (8.3%) of those immunized with TIV S2 and S1, separately.

Seasons with moderately high flu B action, Quadrivalent Influenza Vaccine results appeared to be more compelling than Trivalent Influenza vaccines (Gupta et al., 2012). In South Africa, for example, the cost-efficiency of TIV was as shown from the studies by de Boer et al. (2018), is estimated depending on the assumed attack rate. A review conducted in Australia, Vietnam, and South Africa, by de Boer et al. (2018), introducing 6% of TIV vaccination while assuming a SAR of 5%, showed the decrease in the predominance of the seasonal flu locally by 48.4–50.2%. These reductions included hospitalizations, death, and clinical visits and were the same across all age groups. Additional doses of TIV administered to large groups share a close to the higher outcome linked with QIVs.

Vaccination Cost

The cost incurred can determine the charges of the Influenza vaccine depending on the form of vaccination being directed. The Quadrivalent inactivated vaccine [QIV]) and trivalent inactivated vaccines (TIV) differ in prices, and most low and middle-income countries prefer the Trivalent Influenza vaccines due to their low costs (Neuzil et al., 2017). The direct service delivery cost associated with the cost of the cost related to doctor’s expenses and visits, vaccination of the vaccines in health care faculties can also lead to an increment in the cost of the vaccine compared to the vaccines administered in non-medical administrations such as pharmacies. However, inoculation can be done and managed by lower-wage staff like qualified medical caretakers to decrease medical expenses.

Proof on the expense adequacy of QIV shows that supplanting TIV with QIV would be a significant move economically and beneficial in public health. However, low and middle-class countries have low resources, and their budget can hardly support the transition (Hendriks et al., 2018). De Francisco (Shapovalova) et al. (2015) add that the potential additional benefits derived from Quadrivalent Influenza vaccines are therefore not recognized in these countries because they cannot afford the costs.

Yearly, the expense associated with vaccination, including direct clinical consideration and lost profit, has been assessed at $26.7 billion (Hendriks et al., 2018). The cost of TIV is lower compared to QIV, thus is preferred in numerous Low and middle-income nations. From the research reports made by de Boer et al. (2017), it’s observed that the practice of an extra quantity of TIV prescriptions in low and middle-class countries results in a very close to or higher number of avoided cases of influenza infections than what is achieved through QIV. To determine which vaccine is more effective at a lower cost affordable, some factors such as illness and the practical realities of product availability to be used for immunization systems are considered. Influenza-related costs are grouped into healthcare and non-medical care costs.

The medical services cost constitutes hospitalization expenses, GDP costs, and medication costs. In contrast, non-medical care expenses incorporate expenses incurred from time and profitability losses resulting from work loss (Arefin et al., 2019). The Quadrivalent Influenza vaccine prices are higher than Trivalent influenza vaccines from the study reports across the countries. From the indication on the affordability of QIV, deciding on the selection of QIV over TIV would be a significant choice, especially in enhancing public health. However, in low and middle-income countries with a fixed budget and inadequate resources, this move would cause many financial constraints; that’s why most of these countries consider TIV to be the most attractive option.

Suitable Influenza Vaccine to Use in Lower and Middle-income Communities

Clinical trials to measure vaccine efficacies are being conducted, and efforts to develop an influenza vaccine that is more effective and durable in preventing Influenza disease are underway. In low and middle-income societies, vaccination programs and health care systems are weak. The vaccine deliveries are affected by the poor infrastructure. High-income countries can afford to substitute seasonal trivalent influenza vaccines with quadrivalent vaccines due to resource availability. The Quadrivalent vaccines have an additional health benefit; they are preferred more in the countries that can afford their costs (Ortiz & Neuzil, 2019). However, in countries of lower income, the National budgetary plans and considerations lead to the preference of TIVs due to their low cost. Therefore, determining the most effective vaccine requires the efforts of countries to have knowledge on the benefits and disadvantages of both TIVs and QIVs (Shapovalova) et al., 2015). Influenza A strain causes severe influenza morbidity and mortality rates, according to Newall et al. (2017). Thus, QIVs would be the most financially effective vaccine but, the overall budgetary impact of QIV is higher than that of TIVs.

Due to the lack of funding and financial constraints, high cost-effective vaccines are not prioritized in these countries. When considering suitable vaccines to use in low and middle-income regions, individuals mandated to make decisions feel the context-specific limitations, such as human limitations and available health facilities. The indirect patient efficiency and direct transportation costs incurred during the vaccine dissemination should be considered while assessing the expense of an inoculation procedure and strategy (Neuzil et al., 2017). The Inclusion of productivity costs, dictated by lost time opportunity to patients or guardians, add to the expenses inferable to the program, which will help countries in their cost-effectiveness estimation.

Counting transportation costs paid by people to go for inoculation in clinics will likewise add to the community expenses of the flu immunization strategies (Ortiz & Neuzil, 2019). However, the individual cost in most cases is insignificant thus does not need to be included in the cost-effectiveness estimation strategies. TIV and QIV’s economic value depends on many factors such as influenza epidemiology, vaccine price, and budgetary impact. Assessing these factors will help a country decide on the best vaccination program beneficial both health-wise and helps save the cost.

Discussion of the Results

Each of the articles contained data confirming the economic benefits of influenza vaccination. The points extracted from the search were related to the cost of cases, the number of cases and the intensity of symptoms. The results showed that the results of specially planned studies to assess the economic effectiveness of influenza vaccination demonstrated the profitability of vaccination prevention. At the same time, it was shown that the economic effect of vaccination increases in proportion to the increase in the incidence of influenza.

At the same time, the initial hypothesis was confirmed that the influenza epidemic has the most significant economic consequences for developing countries. In comparison with the studies conducted by European scientists, the results obtained by African and Asian researchers differ. Despite the reduced prevalence of vaccination, in these countries, it has the greatest economic efficiency due to the low GDP of the state.

The strengths of my review are a wide selection of geographical areas used in the study. The economic effects of vaccination were considered not only in Europe but also in developing countries. The weaknesses of the study are the use of data only for large states. This is due to the insufficient number of observations conducted on the economic effects of vaccination in small Asian and African countries.

Policy implications of this study substantiate the costs associated with immunization of people of working age. The data obtained also take into account the specifics of economic processes and the level of medical development of the countries represented in the study. Reasons for further research are to evaluate the cost-effectiveness of influenza vaccination not only using an empirical method but also using situation modeling. In addition, further studies can be carried out using the methodology for calculating the economic profitability of vaccination at different levels of seasonal influenza incidence.


Each country should evaluate whether a seasonal flu immunization program ought to be focused on. Flu immunization programs have been demonstrated to lessen disease, death, and monetary weight on a medical care framework. Nonetheless, they require financial computations, logistics, and political cohesiveness to be effective. Before presenting a seasonal flu inoculation program, nations should consider the possible effect of the occasional flu immunizations on financial plans and available resources. These nations ought to consider whether they have the essential abilities to supply immunization programs. For the program to be fruitful, the wellbeing framework should appropriately handle, store, and administer the vaccines.

The presentation of occasional flu inoculation depends on proof-based choices about the antibody to utilize and when to scatter it fundamentally. To determine which immunization programs are better, nations should evaluate the infection weight and opportunity cost to survey whether the gains exceed the extra investment. Inoculating a larger group of individuals with TIV will increase the health outcome and is a better way of reducing health costs. Choosing whether flu immunization is practical and whether QIV should supplant TIV relies upon the country’s study of disease transmission, monetary plans, financial strains, and the region’s readiness to acknowledge the limited cost. QIVs have extra advantages over TIVs; however, their prices are higher. Thus, in low and middle-income countries, TIVs may remain the more attractive option due to the risk associated with the QIVs, the high price costs, and the production uncertainties.

Thus, in the course of the study it was also determined whether the influenza vaccination program is cost-effective. The key results of the study were evidence of the economic benefits of vaccinated citizens for the GDP of both developed and developing countries. Among the vaccinated citizens, a significant decrease in the number of cases of influenza was revealed, as well as a decrease in its duration and complications. Thus, the main result of the paper can be considered the established savings from vaccination.


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