1. Background
Influenza is an acute infectious disease occurring in sporadic, outbreak, epidemic, and pandemic forms. Type A and B influenza viruses are responsible for the most cases of human illness (1, 2). While type A is related to widespread epidemics and pandemic forms, type B usually leads to sporadic and sometimes epidemic forms. Although all age groups can be infected with influenza virus, children younger than five years old, people older than 60, patients with chronic medical conditions (chronic kidney disease, chronic cardio-pulmonary diseases, and diabetes), pregnant women, and immunocompromised patients are at the highest risk of complications (1-5). In temperate climates, epidemics of the influenza virus occur more in the winter, but in tropical countries, the epidemic can occur throughout the year. It is estimated that these epidemics can lead to about 3-5 million cases of severe disease with serious complications and up to 550 thousand deaths around the world. Droplet nuclei (1 - 4 microns in diameter) remain suspended in the air, and inhalation of droplets situate the viruses in the upper and lower respiratory tracts, finally leading to pneumonia (1, 3-10). Treatment is usually supportive in mild forms, but in patients with severe infection and in those with certain risk factors and chronic medical condition, anti-viral drugs such as rimantadine, amantadine, oseltamivir, and zanamivir can be effective (1-16). Periodically, changing in two viral glycoproteins located in the surface of virus named hemagglutinin (HA) and neuraminidase (NA) can lead to epidemic or pandemic forms of the disease. The results of such periodic changes are antigenic mutants, including antigenic drift of the virus (minor changes) and antigenic shift (major changes). Mutation can occur in one or both surface antigens (HA or NA), and more in the type A of influenza virus. Major changes lead to pandemic of influenza virus (2, 3, 12-18). There are many reports about epidemiology, clinical outcomes, and molecular variation of virus in Iran and worldwide (7-32). Since many contradictory results have been reported in studies about influenza in Iran, it seems that more attention should be paid to such factors as population size, gender, occupation, and underlying conditions. To date, the prevalence of influenza viruses including H3N2, H1N1, and B has not been evaluated well in Iran.
2. Objectives
We aimed to define the epidemiology of influenza in patients who had a positive RT-PCR test and had been registered in the Center of National Surveillance System for Influenza in Mashhad, Iran, in 2019. Meanwhile, we evaluated the rate of disease in patients according to age, sex, residency, risk factors (chronic kidney disease, chronic cardio-pulmonary diseases, diabetes, immunocompromised patients, pregnant women, etc.), vaccination history, complication rate, and clinical outcomes.
3. Methods
3.1. Study Design
In this cross-sectional and descriptive study, we evaluated the files of all patients with confirmed influenza (outpatients vs. hospitalized) referred to the Surveillance System for Influenza in Mashhad, Iran, during autumn and winter of 2019, when influenza virus was prevalent.
3.1.1. Study Area
Razavi Khorasan is a province located in northeastern Iran. Iran’s “National Surveillance System for Influenza” was established in 2004. According to strategies in this system, all patients with flu-like syndrome in different cities of the province should be referred to this center, and nasopharyngeal samples from patients suspected to influenza should be taken and confirmed by PCR.
3.1.2. Study Population
This study was conducted using the files of all patients with confirmed influenza (outpatients vs. inpatients) referred to referral centers in Mashhad from different cities of Khorasan Razavi province.
3.1.3. Sample Collection
A nasopharyngeal swab was obtained for detection of virus by RT-PCR. The samples were placed in transport medium, maintained at 4°C, and sent within 72 h to reference laboratory, where all samples were stored at -70°C. Then, we studied all data related to the confirmed cases, including sex, age, residency, risk factors, history of vaccination, complications, and clinical outcomes.
4. Results:
In this study, a total of 2977 patients (3% outpatients vs. 97% hospitalized) with flu-like syndrome were tested by RT-PCR for influenza during autumn and winter of 2018. Out of 84 outpatients, only two cases were positive for influenza (one patient with Type A and one with type B). Among the hospitalized patients, 80 (51% male vs. 49% female; age range: 1 - 87 years) cases had positive RT-PCR test for influenza. Underlying conditions were identified in nine (10.9%) cases (diabetes: two cases; chronic obstructive pulmonary disease (COPD): one case; chronic cardiac disease: three cases; one pregnant woman; and two patients had a history of seizure). Complications occurred in 18 hospitalizes patients, and pneumonia was the most common complication (17 cases had pneumonia and one case had myocarditis). Death happened in 29 (35.36%) patients and three (33.33%) cases with risk factors. Unfortunately, there was no history of vaccination in our patients. The highest number of patients with influenza (31 [37.8%]) had been reported from district No. 3 of Mashhad municipality, where people have low income and live near the holy shrine, which is a crowded place.
5. Discussion
In this study, 82 cases had confirmed influenza and most of the patients with confirmed influenza were hospitalized people. The results revealed that there was a high rate of disease in certain areas of Mashhad, as well as some cities of Khorasan Razavi province. However, this does not necessarily indicate that these regions are hot spots for influenza virus, because we need suitable indicators to diagnose the clustering of the disease in the mentioned areas. In our study, about 95% of confirmed cases were infected with type A virus, and among the subtyped samples (11 samples), seven cases had virus type A (H3N2) and four patients had influenza type A (H1N1). In a study by Hosseini conducted between 2011 and 2015, out of 7684 positive cases for influenza, 71% of cases were involved with type A virus and 28% of cases had type B virus. In a recent study in 2015, type A influenza virus was the most common type in comparison with other types of confirmed viruses. However, in 2011, type B virus was the most prevalent type among the other viruses (7). The results of a similar study in Australia revealed that type A (71% of cases) was more prevalent in comparison with other types of influenza viruses (29). Another study in Gorgan, Iran by Javid et al. showed that among 790 suspected cases for influenza, pandemic A H1N1, A/H3N2, and influenza B viruses were confirmed in 3.2%, 2.7%, and 2.8%, respectively. In their survey, the greatest number of confirmed cases with RT-PCR occurred in the age group of 25-34 years (30). In our study, the highest prevalence (39%) occurred in the age range of 40-59 years. Also, most death cases happened in patients aged over 60 years and in those having risk factors. In our patients, the disease led to complications in 29% (18 cases) of patients, and pneumonia was the most prevalent complication (17 cases). One patient died due to myocarditis. In the study conducted in Gorgan, among the confirmed cases, 10.3% were male, and 89.7% were female with a mean age of 29.7 years, and there were 22 people aged > 65 years. Li et al. in 2011 showed that the influenza type A was more common in female patients than males (31). However, in our study, influenza was more common in males than females (51.25% vs. 48.75%). In the study by Javid et al. (30), the peak incidence of disease happened in December; considering the age groups and job type, this peak can be attributed to the transmission of influenza virus and other respiratory viruses in schools and universities. Living in crowded places is a serious risk factor for the transmission of virus. A study by Panning et al. showed that crowded places are a major risk factor for transmission of respiratory viral infections such as influenza (32). Fukusumi et al. conducted a study from 2012 to 2015 among engineers, station staff, and train crew at a railway company. This study defined the attack rates for 2012/13, 2013/14, and 2014/15 seasons as 4.7%, 5.2%, and 7.8%, respectively. Also, they showed that the prevalence rate in railway staff was not more than general population, which could be due to a good ventilation in railway stations in Japan and mass vaccination in the company (33). Bus and taxi drivers, bank staff, bakers, barbers, and health care workers are at a higher risk of getting influenza. People working in the transportation companies like airlines, bus drivers, and postal employees are at a higher risk for getting the illness and about 1.5 times more likely to be admitted to a hospital for seasonal influenza compared to other jobs. Food service staff, people working in accommodation jobs, and educators were among 9-10% of the total number of patients hospitalized due to influenza; also, health care workers accounted for more than 16% of all hospitalizations (34). The study by Jaakkola revealed that secretaries, janitors, and cleaners had the highest rate of getting infected with the virus. Secretaries usually have a higher social contact with people, and they are more at risk for infection. Shared office space has been shown to increase the risk for influenza, common cold, and other respiratory viruses (35). Unfortunately, there was no data about occupation in our registered patients. Pregnant women are susceptible to severe influenza. Physiologic changes related to pregnancy, such as decreased cell-mediated immunity, can increase susceptibility to infection in pregnant women. During the H1N1 pandemic in 2009, severe flu infection among postpartum women (delivered within previous two weeks) was reported (36, 37). In a case series conducted in 2009 during H1N1 pandemic, 20% of deaths were reported among 280 pregnant women admitted to intensive care units (ICUs) (36-39). In the present study, only two pregnant women were reported with influenza, one of whom died due to severe disease and pneumonia. Certain environments such schools, universities, and meetings can accelerate the transmission of the virus. This happens commonly in crowded and contaminated spaces in which the virus is more likely to spread through direct contact. Therefore, shared workplaces and schools can cause flu outbreaks and epidemics, if the employees do not stay home when they are sick and have an active infection. In our survey, the highest number of patients with influenza had been reported from district No. 3 of Mashhad, where the people have low income and live near holy shrine, which is a crowded place. Similarly, Panning et al. reported that crowded places can increase the transmission of flu infection from patients to others (32).
5.1. Conclusions
Our results showed a high prevalence of complication and death among hospitalized patients, especially those without any risk factor for influenza viruses. Therefore, comprehensive vaccination programs and promotion of knowledge about transmission routes are two important factors for disease prevention and lower death rates. Further studies about the risk factors, history of vaccination, job type, and virus type and subtype are recommended in Iran.
5.2. Strengths
The Iranian “National Surveillance System for Influenza” was established in 2004. It is a national system used for sixteen years to collect all data about patients with influenza like illness (ILI) and influenza infection referred to health centers and hospitals in capital cities of Iranian provinces. The use of such data is a unique approach to provide better information about disease and patients. It is important to teach staff and improve their activities for collecting data and better surveillance.
5.3. Limitations
The main limitations of this study were as follows:
1- Many patients with mild influenza, such as health care workers, may not refer to a laboratory for confirmation of infection.
2- Due to the widespread nature of the flu and since most people do not take treatments, our results cannot reveal a real estimate of the prevalence and clinical outcomes of the disease.
