A Retrospective Public Health Assessment and Management in Terms of the Social and Clinical Risk Factors of Respiratory Syncytial Virus Infection in Northern Canada

Background The predominant source of respiratory infections in Northern Canada stems from RSV, leading to potentially life-threatening lower respiratory tract infections in children below the age of 2. Typically, RSV begins to appear in November or December and persists until April or May. Synagis® (Palivizumab), a monoclonal antibody, is employed to mitigate or reduce the effects of RSV. Past research indicated a reduction in hospitalizations with the use of Synagis®. Aim The aim is to estimate the cost-benefit analysis by comparing the health services cost with Synagis® program cost. Also evaluate the association of identified risk factors with the severity of RSV infection. Material and methods The dependent variable is categorized as: “Mild-Medium” cases that didn’t undergo intubation or require medical evacuation; “Severe” cases that underwent intubation, required medical evacuation, and intensive care unit facilities. We also calculate the cost of health services and Synagis® of each year. Results It has been found that babies who exclusively breastfed and regularly took vitamin D did not develop severe forms of infection. Prenatal smoking and shared and crowded accommodations contribute to the spreading of RSV. The average cost of health services per participant was higher than that of the Synagis program. Conclusion They are promoting the Synagis® program during the season. Standardize the regulations prohibiting smoking around small children since they are more vulnerable to infection. Practice breastfeeding up to 24-month-old babies.


Introduction
The first chimpanzee to show cold symptoms from a respiratory syncytial virus (RSV) infection was reported [1].The RSV infection was discovered shortly after in Baltimore in small infants who had symptoms of severe respiratory illness [2,3].Babies throughout the globe get RSV most often, making it the top cause of pneumonia and bronchiolitis [4].RSV infection caused 3.4 million hospital admissions up till 2011 and around 66,000-199,000 fatalities annually throughout the world [5].
Due to different infection patterns and sickness with another well-known respiratory tract viral disease, RSV presents various challenges for epidemiologists [4].RSV usually starts to manifest in November or December and lasts into April or May [6].In Northern Canada, particularly in Nunavut, it is one of the leading causes of lower respiratory tract infections, which may have catastrophic outcomes such as bronchitis, bronchiolitis, and pneumonia [7].
A monoclonal antibody called Synagis® (Palivizumab) is used to counteract or lessen the impact of RSV.Previous studies showed that Synagis® decreased hospitalization by 55% for preterm babies with Broncho Pulmonary Dysplasia (BPD) [8].
Infant RSV infection is a frequent reason for medical flights in Nunavut to provide treatment.Children who need critical care must be transported to Qikiqtani General Hospital in Iqaluit or through Medevac or Schedevac to other authority hospitals in Southern Canada.Synagis® is used in young children under the age of two during the RSV season to lower the morbidity and death risk associated with RSV in babies.However, to ensure safety and boost protection against infection, each kid must get monthly vaccine doses during the entire RSV season.
According to the literature study, several variables might raise or reduce a child's chance of contracting an illness before the age of two.It has been shown in previous research that breastfeeding exclusively protects against RSV [9] and that children who are not being breastfed or are not being exclusively breastfed have a greater risk of infection [10].Smoking has been connected to a higher risk of RSV during or before pregnancy [11,12].
Smoking during pregnancy by mothers increases the likelihood of developing a severe RSV infection.
Smoking inside has been connected to a higher risk of RSV [13][14][15].There was a very high risk of RSV infection in school-aged siblings [12][13].The risk of catching RSV is higher in households with more than two people.Sharing a bedroom with another person also increases the risk of catching RSV [13].
The aim of the study is to determine the health services costs related to RSV infection and Synagis® program cost during the five-year data in order to estimate the cost-benefit analysis by comparing the cost of health services with Synagis® program cost in order and evaluate the association of identified risk factors with the severity of RSV infection.

Sample
For this study, we looked back at data from all babies in Nunavut towns who had a confirmed case of RSV between 2011 and 2016, specifically those between 0 and 24 months old.The data were collected across a five-year period.

Test Details
Nasal swab collection was used to take the samples and use Rapid RSV antigen test to confirm the RSV cases.

Databases
The Health Protection Unit of the Government of Nunavut maintained the Nunavut Influenza and RSV Enhanced Surveillance Database, which included records of laboratory-confirmed cases of RSV together with demographic information.
This study drew on data extracted from the Discharge Abstract Database (DAD), a repository of information on patient discharges from all Canadian healthcare institutions maintained by the Canadian Institute for Health Information.The data included hospitalization records, intubation markers, and associated expenses.
The database of all medical travel covered by the Nunavut Health Insurance Program was queried to acquire information on medical travel, including cost.Data about Synagis® was sourced from the Nunavut Synagis® Database maintained by the Health Protection Unit of the Government of Nunavut.The Health Protection Unit of the Government of Nunavut covers the cost of Synagis®.
MEDITECH, Nunavut's electronic medical health record system, was queried for information on emergency department visits, including temporary health condition numbers (HCNs) and risk factors.We searched the patient's MEDITECH file for pertinent information in the following places: reports of pediatrician consultations, discharge summaries, well-baby records, and healthcare visits.
The Canadian Institution of Health Information provides the average cost of a standard hospital stay broken down by province and territory.

Variables
We used "severity of infection" as the dependent variable and divided cases into two categories: "Mild-Medium" cases were those who did not undergo intubation and did not require medical evacuation because of RSV infection; "Severe" cases were those who underwent intubation.The risk variables we considered were history of breastfeeding, exposure to prenatal and postnatal cigarette smoke, birthweight, gestational age at birth, history of vitamin D consumption, presence of other children at home, type of housing, number of households, and history of CHD, BPD, and CLD.Refer to the Supplementary table to check the inclusion criteria.The complete details of the variables and their respective definitions are explained in the Supplemental table.Refer to Figure 1 for study design and methodology.

Data Analysis
The data entered and verified in Microsoft Excel before export to SPSS version 24 (IBM Corp., Armonk, NY) for analysis, underwent rigorous scrutiny for accuracy and consistency.Data were summarized by descriptive statistics in the form of case counts and proportions.

Cost Analysis
Using data on hospitalization, medical travel, and emergency department visits broken down by respiratory season, we were able to determine the average cost of medical services.Age, season of infection, and severity will also be used to stratify the average cost of medical treatments.For each year that a patient was a part of the Synagis® program, we determined the overall cost.Regarding the cost computation, please see supplementary table.

Risk factors with the severity of RSV infection
We conducted the bivariate unadjusted analysis between the severity of infection (mild-medium vs severe) with predictor variables to screen the variables for the multivariate regression (significance level p-value less than and equals 0.20).We performed multivariate logistics regression between the outcome variable and the predictors significantly associated with bivariate analysis (significance level: p-value less than 0.05).The missing values were treated through multiple imputation methods to improve the significance level.

Descriptive statistics
Table 1 summarizes the descriptive analysis of five-year retrospective data concerning the severity of infection.Out of 461 total cases for five years, 219 cases were female, and the rest were male infants; among them, 32% were female infants, and 31% were male infants who were severely infected with RSV.The most represented age group among infected cases was from the Inuit ethnic background and the Qikiqtaaluk region; among them, 62% and 30%, respectively, were severely ill with RSV.In the study of infants, 31% were those who were severely ill and never breastfed in their early lives.57% and 61% of infants were those with prenatal and postnatal tobacco exposure and were severely infected with RSV.Our data indicated that there was no association between birth weight, CLD, post-natal smoking, and developing RSV infection among study children.However, postnatal smoking has a potential confounding effect on predictor variables; therefore, we have included it in the model.

Health Services Cost
A total of around $5,625,649 was spent on all medical treatments over the five-year period of RSV infection, with an average cost of about $12,203 per case, according to the data.With regard to the season of infection, Table 3 displays the overall expenditures of medical services together with an average cost per case.Additionally, Table 3

Cost-Benefit Analysis by Comparing Health Services and Synagis® Program Cost
Over the five years that RSV was common, Table 4 breaks down the overall cost of medical services associated with the virus as well as the cost of Synagis®.On average, each participant spent roughly $7,414 on Synagis® and around $12,203 on RSV.

Discussion
Through the descriptive test, it was discovered that there was no significant difference in the number of RSV cases among males and females.Instead, parents of infants between the age group of zero to five months had a higher likelihood of having their children tested and expected to visit a doctor.However, this is also possible because infants under six months have lower infection resistance than children in other age groups.
In addition, Qikiqtaaluk is a larger region in the Nunavut territory than the other two regions, so the proportion of cases there was higher than in Kivalliq and Kitikmeot, as expected due to the higher resident populations.Additionally, Qikiqtani General Hospital, located within this region, may cause more RSV cases in Iqaluit.Similarly, Inuit make up 85% of Nunavut's population, which may explain why there are more instances (456 cases) among Inuit people than among people of other ethnicities.
An increased number of cases (129 in 2012/13) is likely responsible for the greater cost compared to other infection seasons, according to the data.Seasons 2015/16 and 2014/15 had higher average costs per case ($17,587 and $16,122, respectively).A larger percentage of patients handled outside of the area, as well as increased travel and hospitalization expenditures, are the reasons for this.
The examination of this study's data revealed that individuals with a history of nursing had significant outcomes; these cases had higher instances of severe levels of infection than those who were exclusively breastfeeding.Another notable effect of prenatal smoking is that moms of young children who smoked before or during pregnancy had more RSV infections than mothers of children who never smoked.Additionally, a weak correlation and confounding impact with RSV were reported for postnatal smoking.
The number of persons living in the home also had a significant impact on the prevalence of RSV; these instances were more prevalent among households with two to five occupants.According to earlier research, if there were more school-going children present with young children or newborns, the chance of RSV would be increased.Other kids who lived with the sick kids at home also showed noteworthy associations with the illness.

Limitations of the study
The instances examined in this research involved RSV cases confirmed in the laboratory, which may lead to a potential underestimation of the true number of RSV cases.Not all individuals in the Kivalliq and Kitikmeot regions were swabbed for RSV due to the absence of specific facilities.This could potentially result in an underestimation of the true number of RSV cases in those two regions or an overestimation of the cases in the Qikiqtaaluk region.The Qikiqtani General Hospital, located in the Qikiqtaaluk region, might potentially record a higher number of hospitalized cases from the Qikiqtaaluk region, including a greater number of medium-severity cases.This is because individuals with mild RSV symptoms may also be hospitalized, contributing to the overall count.

Conclusions
The impact of RSV requires a comprehensive approach that emphasizes the promotion of exclusively breastfeeding, the avoidance of prenatal and postnatal smoking, and the recognition of the benefits of Synagis immunization.Advocating for these measures not only can enhance the overall health and wellbeing of infants, but also contribute to substantial financial savings and a reduction in the burden of RSVrelated diseases to the Government of Nunavut, Canada.Embracing these strategies collectively serves as a crucial step toward safeguarding the vulnerable population and fostering a healthier future for Northern Canadian communities in the Territories.Through a cost comparison, it is evident that RSV infection imposes a significant financial burden on the Government of Nunavut.Implementing the Synagis Universal program would alleviate this cost burden for the government.

Recommendations
Compared estimated cost of the universal Synagis® program, including the medical cost for the estimated no. of cases assuming effectiveness is similar in the general population.Estimated cost for universal Synagis® program = % of cases among Synagis participants (mild, medium, severe) x total population 0-23 months x average cost incurred per case (mild, medium, severe).
Place greater emphasis on minimizing the risk factors associated with RSV by collecting additional data that can comprehensively assess the overall risk scenario.In this context, formulate policies aimed at reducing smoking indoors or in the presence of young children, who are particularly vulnerable to infections.
Persist in endeavors to tackle risk factors; initial associations with risk factors indicate a heightened prevalence of tobacco smoke exposure among RSV cases and milder infections among cases exclusively breastfed for a minimum of two months.

Future activities of this program
For future reference, it is advisable to collect all risk factors beyond those available in the Meditech database, including information presented in paper charts, etc.Additionally, explore the associations between these risk factors and RSV infection.It is also recommended to investigate how these risk factors may impact the severity of infection by comparing hospitalization (with or without intubation) and nonhospitalized patients on a larger scale.

TABLE 1 : Descriptive and bivariate unadjusted analysis between predictors and level of RSV infection
There were 20% of cases severely ill with RSV lived with six to 10 people at home, and among them, 48% of severe cases lived with other children at home, and 55% of severely ill cases lived in shared accommodation.In the study infants, 43% of infants with severe RSV were born premature (gestational age < 36 weeks), and 41% were those with lower birthweight (<2,500 grams).37% of severe RSV cases never intake vitamin D, 25% of severe RSV cases had a condition of CLD, and 28% of severely infected RSV cases had a condition of CHD.

Table 1
also shows the unadjusted bivariate analysis between risk factors and the level of RSV infection.All the predictor variables other than age and ethnicity were significantly associated in unadjusted bivariate analysis.So, we excluded the age and ethnicity in the adjusted multivariate regression model.

Table 2
The odds of developing RSV infection among young infants who never take vitamin D were 0.371 times the odds of developing among those who always take vitamin D (P-value<0.05; 95% (Cl: 0.177-0.774).The odds of developing RSV infection among children with CHD condition were 3.66 times the odds of developing RSV who did not have any CHD condition (P-value<0.05,95% Cl: 2.208-6.085).The odds of developing RSV among children who lived in shared accommodation were 2.81 times the odds of developing among those who lived in private accommodation (P-value<0.05;95% (Cl: 1.162-6.780).
represents the multivariate logistics regression between the severity level of RSV infection (outcome variables) and risk factors (predictor variables) gathered from past literature.The odds of developing RSV among infants who never breastfed was 2.282 times the odds of developing RSV who exclusively breastfed (p-value<0.001;95% CI: 1.254-4.154).The odds of developing RSV among children whose mothers had prenatal use of tobacco smoking were 4.45 times the odds of those who were not exposed to tobacco smoking (P-value<0.05;95% (Cl: 1.511-13.134).The odds of developing RSV infection among infants who live with other children at home were 2.65 times the odds of those who did not live with other children at home (P-value<0.05;95% (Cl: 1.404-5.007).The odds of developing RSV among infants who live with more than ten people at home were 3.168 times the odds of those who live with 2-5 people at home (P-value<0.05;95% (Cl: 1.651-6.081).2024 Sharif Sheikh et al.Cureus 16(2): e53378.DOI 10.7759/cureus.¥:P-value < 0.05; ‡: P-value<0.001;ns: not significant; €: Confounding effect; Ref: Reference category AOR: Adjusted odd ratio; 95% CI: 95% Confidence Interval

TABLE 4 : Comparison of Synagis® & Medical Services due to RSV by Year of Infection
All the cost were in Canadian Dollar caregiver's unique lifetime identifier for Nunavut Health Insurance Registry, used to identify clinical utilization records for patient prior to being assigned own HCN YYYY Symptoms onset date for RSV infection, prior to positive swab collection.If not available, date four days prior to swab collection date was used as proxy listed in hospital record that refers to the estimated resource utilization of an average patient during hospitalization, as defined by the Canadian Institution of Health Information.Used to calculate estimated hospitalization cost if no hospital cost included in record.Synagis® doses administered to patient during the respiratory season in which RSV infection occurred.Further information on cost calculation included in cost table (below).Child's Risk Factors For severe RSV/Clinical For infants, older than 2 months, indicator of breastfeeding history of patient as reported by caregiver.From the birth, up to the time of infection Exclusively: only breastmilk, no formula fed to patient for more than two months Not exclusively: breastmilk fed to patient in addition to formula and/or other milk products, or exclusive breastfed for less than two months.Never:No breastmilk fed to child, only formula and/or other milk products patient lives with individuals who smoke tobacco inside of the accommodation, reported at any time prior to swab collection date.No. of Household 2-5, 6-9, ≥10 Number of people who typically reside at patient's primary residence as reported by caregiver.Indicator whether patient was prescribed but given Vitamin D supplements reported at any time prior to swab collection date.Never: never given Ever: given at least once Sometimes: given at least monthly Always: given at least five times a week Type of Accommodation Private or Shared Private: only patient's immediate family shared the primary accommodation; Shared: patient's primary accommodation shared by individuals other than patient's immediate family.
Indicator of whether patient was up-to-date with Synagis® vaccination at time of RSV infection.Determined by the number of days between date of last dose and date of swab collection.2024 Sharif Sheikh et al.Cureus 16(2): e53378.DOI 10.7759/cureus.5337811 of 14 Cost of Synagis® Numeric Total cost of