Acute respiratory tract infections among hospitalized Palestinian patients: a retrospective study

Background: Respiratory tract infections (RTIs) are a major public health concern. This study aims to investigate the profiles and epidemiological characteristics of acute RTIs and respiratory pathogens in Palestinian hospitalized patients. Methods: Clinical samples from hospitalized patients with symptoms of acute RTIs admitted between January 2011 and December 2016 are referred to Palestinian Central Public Health Laboratory (PHCL) to identify the causative pathogen. Patients’ demographic information and the results of the molecular identification were retrieved from the electronic database at the PHCL. The results of the detections were analyzed to explore the distribution of pathogens resulting in hospitalization among patients with RTIs across age, gender, region, year and season. Results: A total of 15413 patients with acute RTIs were hospitalized during the study period. The causal agent was identified only in 28.7% of the patients. Overall, influenza viruses were the most common cause of RTIs among hospitalized Palestinian patients in the West Bank. The elderly population (≥60 years old) had the highest rates. Respiratory syncytial virus (RSV) and Bordetella pertussis (B. pertussis ) followed influenza, respectively. Children showed the highest hospitalization rates for these two infections along with adenovirus, enterovirus and Streptococcus pneumoniae. Outbreaks of RTIs occurred mainly during winter (between December and March). Conclusions: Influenza viruses are the major cause acute RTIs among hospitalized patients in the West Bank. Children and elderlies have the highest risk for RTIs. The reoccurrence of B. pertussis in spite of vaccination is alarming and requires further investigation.


Background
Respiratory tract infections (RTIs) are considered to be the most common infectious diseases worldwide and the second leading cause of death among children under five years old [ 1 , 2 ]. In Palestine, infectious diseases contribute to less than 10% of all deaths; respiratory diseases (ICD10 code: J00 -J99.9) contribute to 70% of those deaths with a mortality rate of 17.0 per 100,000 population during 2016, being the sixth most common cause of death [ 3 ].
The etiological agents of respiratory diseases include a wide range of respiratory viruses and bacteria. They appear with a spectrum of symptoms that include fever, cough, malaise and chest pain. Rapid interventions are necessary as these infections could result in either mild illness, or could lead to severe complications, hospitalization and death [ 4 , 5 ]. Identification of the causative agent of respiratory diseases based on signs and symptoms alone is not reliable. Therefore, understanding the epidemiology of RTIs and identification of the patterns and etiologies are critical for successful treatment and prevention programs [ 6 ] . The purpose of the current study was to investigate the profiles and epidemiological characteristics of acute RTIs and respiratory pathogens in hospitalized patients in the West Bank, Palestine.

Results
A total of 15413 Palestinians patients were hospitalized between 2011 and 2016 with acute RTIs. The mean incidence rate of hospitalization for acute RTIs in the West Bank during this period was 91.4 per 10 5 population with a range between 34 and 149. Table 1 shows the demographic characteristics of the cases. Acute RTIs were equaly common among males and females but the highest incidence rates were seen among children less than 10 years old and elderlies (55 years of age or more). The mean age of cases was 32.8 years. During the six years of the study, hospitalization for acute RTIs increased, but a drop was recorded during 2014. Overall, hospitalization rates were highest in the northern governorates of the West Bank.
During the study period, the causal agent was only identified in 28.7% of the referred cases. The highest detection rate was for RSV followed by influenza A viruses ( Table 2).
When we compared the hospitalization rate of each organism between males and females, we didn't detect significant differences ( Table 2). Influenza A was the major cause of acute RTIs among hospitalized patients ( Table 2).  (Table 3). Hospitalization rates of influenza A virus increased with age, especially after the age of 60 years (Fig. 1c). The highest number of cases was recorded during cold months; December and January (Table   4). There were no cases of avian flu (H5N1) recorded during the period between 2011 and 2016, but swine flu (H1N1) was relatively common with a total of 1373 confirmed cases.  (Tables 2 and 3). The highest rates were seen in northern governorates ( Table 5). As for influenza B, hospitalization rates were relatively low, being highest during 2011 ( Table 3).
The second major cause of hospitalization for RTIs was RSV ( Table 2). The highest hospitalization rates were among children <5 years old (Fig. 1e). The rates were highest during 2016 and 2014, respectively (Table 3). Further, the central governorates recorded three-fold higher rates as compared to northern and southern ones (Table 5). Like influenza A, most cases occurred during December and January (Table 4).
Regarding pertussis cases, they were mainly children and the highest rates were seen among those between 5-9 years old (Fig. 1a). During 2012, hospitalization rate was almost five times higher compared than the other years. Since 2013, a gradual increase in hospitalization rates was observed (Table 3). About half the number of cases occurred during spring (March-June) ( Table 4) and the central region showed the highest rate while the lowest rates were observed in the south (Table 5). 6 During the last few decades, a shifting in the burden of diseases from communicable to non-communicable diseases has been noticed in many developing countries. Nevertheless, infectious diseases continued being a major cause of morbidity and mortality among Palestinians, especially children under 5 years old [ 3 ]. In developing countries, B. pertussis, enteroviruses, influenza viruses, RSV, adenoviruses, and S. pneumoniae are considered to be the main causes of RTIs resulting in 4-5 million annual deaths among children only [ 7 ]. This study investigated the most common causes of acute RTIs among hospitalized patients in the West Bank. The data obtained through this study are population-based and therefore useful for predicting pathogen patterns and disease burden, in addition to planning for vaccine research and control strategies.

Discussion
During the study period, 15413 cases of severe acute RTI cases were hospitalized at the Palestinian hospitals in the West Bank. Hospitalization rates were high during the study period and increased from 2011 to 2016. The majority of RTI cases were caused by influenza, followed by RSV. Similar patterns were reported worldwide [5]. Data from the surrounding countries are limited and were incomparable to our study. For instance, a study conducted in Amman, the capital of Jordan, reported RSV to be the most common viral cause of respiratory tract infections among children [ 8 ]. On the other hand, in Beirut, Lebanon, human rhinovirus, RSV, human bocavirus, human metapneumovirus and human adenovirus were respectively reported as the most common causes of RTIs among hospitalized children [ 9 ], while in the Egyptian Delta, influenza was the major viral cause of RTIs while RSV was reported as the major cause among children [ 10 ].
Our findings show that the largest proportion of hospitalized patients was children less 7 than ten years old, but the highest hospitalization rates were among the older population. This is simply explained by the fact that the Palestinian population is a young population with one quarter the population being less than ten years old [ 11 ].
Although the highest number of cases was associated with influenza A; most cases of RSV, adenoviruses, B. pertussis and enteroviruses occurred in children less than ten years old.
These organisms were previously reported to be most common among children [ B. pertussis is a vaccine preventable disease that used to be considered as a universal infection among children less than 5 years old. The infection was reported to kill one in ten infected children in the United States during the 1920s. Whole-cell pertussis vaccine was available since 1940s, and during the nineties it was replaced by acellular vaccines.
Studies have shown that immunity against pertussis is not life-long [ 8 20 ]. In Palestine, vaccination against B. pertussis is a part of the Expanded Program on Immunization and is given in combination with vaccines against tetanus, diphtheria and Hib at the ages of 2, 4 and 6 months, in addition to a booster dose at 18 months. Our study shows that B. pertussis is still considered a major cause of morbidity in the West Bank. Outbreaks of the disease have been reported worldwide regardless of the high vaccine coverage [ 20 , 21 ]. Studies showed that the waning immunity results in a peak in the incidence of pertussis among school-age children, and the infection spreads from these subjects to infants or not-fully vaccinated young children [ 21 ]. In addition, changes in the circulating strains of the bacterium should be considered [ 20 , 21 ]. Our findings showed similar patterns. The severity of infection among infants is the highest [ 20 ]. In this study we only included hospitalized patients, reflecting severe cases of the disease, and excluding mild, non-hospitalized cases who are probably older (adolescents and young adults).
In contrast to RSV and pertussis, influenza cases occurred mostly in elderly population, a pattern of influenza that has been previously demonstrated [ 22 , 23 ]. Similar findings were reported in the Egyptian Delta, where influenza was the major cause of acute RTIs and was most common among individuals 65 years old or more [ 10 ]. Furthermore, in our study, a distinctive pattern of influenza A virus was seen through the study years; a drop in the rate of hospitalized cases of influenza A during  36 ]. Explanation of the seasonality of infections has been hard. One of the hypothesized explanations states that these seasonal outbreaks are a result of overcrowding indoors with the lack of proper ventilation during cold seasons. In addition, low temperature and dry conditions were found to be favorable conditions for pathogen transmission in animal studies, which is consistent with indoor state [ 37 , 38 ]. The hospitalization rates from other organisms were very low during the study period. Therefore we were unable to review patterns and trends accurately.
In summary, RTIs are still a public health concern, especially among children and elderly populations. Influenza viruses are the major cause of respiratory diseases among Palestinians. RSV is the most common cause of pediatric RTIs while influenza is the major cause among the elderly population. In addition, B. pertussis is still a common cause of RTIs among children regardless of the vaccination policies.
This study is the first to describe RTIs in Palestine and is one of the largest studies in the neighboring countries. The study included all MOH hospitals in the West Bank, which is the main healthcare provider in Palestine. In addition, the study covered a period of six years; which was suitable to capture changes in the trends of the disease. Regardless, one of the limitations of this study was including only hospitalized patients in MOH hospitals without considering outpatients and patients in other hospitals, inclusion of these cases could have provided more comprehensive and representative view on the patterns of RTIs.
Furthermore, some common respiratory tract infections were not examined here as they are not part of the diagnostic tests such as human rhinovirus, human bocavirus and human coronavirus. Moreover, clinical characteristics of the cases and disease outcomes were not considered in our study. Coinfection with two or more pathogens is another missing entity in this study.

Conclusions
We compared the spectrum, seasonality, and age distribution of common causes of RTIs among Palestinians in the West Bank. Our data showed that viral agents caused the majority of respiratory diseases. Further surveillance and follow up on the epidemiology of these diseases is recommended. In most cases of RTIs, the causal agent was Therefore, no approval from an ethics committee or informed consent from patients was required for this study.

Consent for publication
Not applicable.

Availability of data and material
The data that support the findings of this study are available from The Palestinian Ministry of Health but restrictions apply to the availability of these data, which were used under 13 license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of The Palestinian Ministry of Health.

Competing interests
The authors declare that they have no competing interests.