Acute gastroenteritis (AGE) is a prevalent childhood condition that places a heavy burden on healthcare systems, particularly in low- and middle-income countries (LMICs). It is characterized as a syndrome of nausea, vomiting, diarrhea, and abdominal discomfort with an underlying infectious etiology [1]. Three or more bouts of loose, watery stools in a 24-hour period meet the World Health Organization’s (WHO) criteria for diagnosis [2]. Estimates show that acute diarrhea alone causes more than 1.5 million outpatient visits, 200,000 hospitalizations, and 300 fatalities per year in the United States (US) alone. It is important to note that when third-world countries are taken into consideration, diarrheal diseases are responsible for about 2 million deaths annually [3]. Most AGE patients only require minimal medical attention, although in rare circumstances hypoglycemia and severe dehydration may occur [4]. Despite the slight differences across various geographical zones, AGE management is a global endeavor. The gold standard for treating patients with acute gastroenteritis (AGE) who seek medical care remains supportive therapy, with oral rehydration solutions playing a central role in fluid replacement [1].

Rotavirus is the most common enteric virus that causes pediatric AGE [5]. A meta-analysis demonstrated the enormous impact of rotavirus AGE, showing that 111 million episodes required home management, 25 million clinic visits, 2 million hospitalizations, and a median of 440,000 deaths annually worldwide [6]. Another analysis showed a total of 215,000 deaths attributed to rotavirus AGE in 2013, with India, Nigeria, Pakistan, and the Democratic Republic of Congo accounting for approximately half of deaths in the same period [7]. The clinical spectrum of rotavirus infection can manifest as anything from a preclinical illness to frequent, excessive vomiting and diarrhea that can cause shock, electrolyte imbalance, and even death [8]. Rotavirus vaccines licensed in 2006 have gained approval as being strongly recommended [5][9]. A decreasing incidence of rotavirus cases has been detected by a rate of 57% - 89% annually [10].

In 2015, the Rotateq® vaccine was introduced to the Jordanian national immunization program, and it is given in three separate doses at the 61^st, 91^st, and 121^st days of life [11]. Worth mentioning, children on Jordanian grounds are all eligible for the Jordanian national immunization program vaccines, and childhood vaccination is mandatory. Prior to the introduction of the vaccine, the prevalence of rotavirus AGE in children below the age of five was 39.9% [12]. To the best of our knowledge, there is no large cohort study evaluating the efficacy of the rotavirus vaccine among Jordanians or assessing the impact of vaccination on the clinical course of rotavirus cases. In this retrospective analysis, we sought to determine the significant clinical manifestations among patients as well as the prevalence of rotavirus as a causal agent of AGE after the introduction of rotavirus vaccination. In addition, we aimed to compare the clinical and laboratory manifestations between Rota and Non-Rota gastroenteritis.

This retrospective study aimed to investigate the prevalence of acute AGE cases at a tertiary care center and to assess the burden of rotavirus as a causative agent for AGE following the introduction of the rotavirus vaccine. This is an observational retrospective study. The study was conducted at King Abdullah University Hospital (KAUH) between 1^st January 2015 and 31^st December 2020. The center, in collaboration with other healthcare facilities, is the sole tertiary care facility in northern Jordan that provides care for more than 2 million people. Northern Jordan also hosts a substantial Syrian refugee population, among whom childhood vaccination coverage—including rotavirus vaccine—is variable. This represents a potential confounder in interpreting vaccine impact.

Although the global incidence of AGE has declined due to improved hygiene and vaccination [15], AGE continues to be a significant global health issue, leading to mortality primarily in sub-Saharan Africa and South Asia, despite the availability of cost-effective treatment options [16]-[18]. Our study highlights that rotavirus continues to be a major causative agent of AGE requiring hospital admission despite the vaccination measures taken in our community. Herein, 709 AGE attacks were included; 33.4% were due to rotavirus. Neither vital signs nor growth parameters differed between the causes of AGE. Patients with rotavirus AGE were more likely to have vomiting episodes per day compared to other causes of AGE. It is evident that rotavirus vaccination could be protective against rotavirus AGE. Raised hematocrit, urea, creatinine, and Na⁺ levels indicated more severe dehydration caused by rotaviral illness.

In our study, almost one third of our patients were due to Rota infection. The second identified microorganism was E. histolytica (13.6% of the non-rota AGE). Of note, 84.1% of non-rotavirus AGE cases lacked an identified pathogen. Given the limited viral diagnostics available, it is likely that norovirus, adenovirus, astrovirus, and sapovirus account for a significant portion of these ‘other’ cases. The facilities to identify viruses other than Rota were not available in our facility. Our results contradict what Salami et al. reported in Lebanese children; E. histolytica was the leading microorganism [19]. Rota was responsible for 13.6% of the cases. We believe that sanitation conditions might be responsible for the discrepancy in E. histolytica rates, while the lower rates of Rota infection could be due to the younger age group of their cohort. Interestingly, an older study by Yuosef and colleagues on children below 5 with acute gastroenteritis presented to the pediatric hospital in Northern Jordan showed that Rota was responsible for almost one third of the cases, and E. coli subtypes were responsible for the other one third of the cases [20].

The clinical presentation of patients is variable. Viral AGE mostly results in non-bloody watery diarrhea with low-grade fever, in contrast to bacterial AGE, which results in bloody diarrhea, high-grade fever, and leukocytes in stool samples [21][22]. The peak age is below 2 years, and the mode of transmission is fecal-oral or respiratory. The degree of dehydration can be determined by the clinical presentation of patients, such as weight loss. In mild to moderate dehydration, oral rehydration solutions were equally effective when compared with the intravenous counterpart when weight gain, duration of diarrhea, and hospitalization period were taken into consideration. In cases of vomiting and refusal of oral hydration, continuous nasogastric application is as effective as intravenous rehydration [23]. In the present study, although included, physical signs of dehydration were considered a less reliable mode of determining and comparing the dehydration status, due to the cross-sectional nature of the study and variability among reporters. This discrepancy may arise from the subjective nature of parental assessment, recall bias, or underestimation of insensible losses, whereas laboratory indices provide an objective biochemical measure of dehydration severity. Additionally, rotavirus-related dehydration may develop more rapidly, leading to disproportionate biochemical changes despite similar clinical impressions. Therefore, laboratory parameters were used to indicate the severity of dehydration among the two study groups, including hematocrit (P = 0.001), urea (P = 0.003), creatinine (P = 0.002), and Na⁺ levels (P = 0.026). This is consistent with previous reports that Rota is more likely to cause dehydration compared to other microorganisms [24][25].

According to Tafalla et al., rotavirus was responsible for 38.1% of all cases of AGE, and 40.7% of those cases were classified as severe. In contrast, only 19.5% of patients who tested negative for rotavirus experienced severe symptoms [26]. Similarly, Almatti’s study in Jordan showed that rotavirus accounted for 35% of all cases of AGE [27]. Additionally, Nafi found that 39.9% of children, mainly those under two years old, were ELISA-positive for rotavirus in their stool samples [12]. In another study by Meqdam et al., ELISA assay detected rotaviruses in 39.6% of cases [28]. The present study indicated that rotavirus was the cause of 33.4% of all cases of AGE. Although such numbers might be interpreted as a non-effective vaccination program, we believe that our numbers might be affected by the fact that our hospital is the referral center for North Jordan and is surrounded by a couple of pediatric hospitals that deal primarily with less severe conditions. In addition, as North Jordan is the main host for Syrian refugees, the influx of unvaccinated children might result in diluting the effect of vaccination in Jordan.

It is evident that rotavirus AGE cases vary across time and geographical locations [29]. Rotavirus infection is seasonal in temperate climates, peaking in late winter, but occurs throughout the year in the tropics [22]. As stratified cases, AGE shows no seasonal variation; however, rotavirus AGE was clearly more prominent during the period between March and May [26]. Similar seasonal variations were observed as well in a Polish study by Toczylowski et al., in which peak prevalence was between February and May [30]. In Pakistan, most of the cases were during June, October, and November [31]. Correspondingly, bacterial AGE tends to vary considerably during the year, predominating amidst warmer weather, and more frequently being foodborne [21]. In our study, the rate of rotavirus cases peaked in May.

Sun and colleagues conducted a meta-analysis that showed that both Rotarix and RotaTeq vaccines were effective in reducing the risk of rotavirus and rotavirus-associated hospitalization in fully vaccinated children, especially those with severe symptoms [32]. Likewise, Burnett et al. found that the effectiveness of the Rotarix vaccine against laboratory-confirmed rotavirus was 86%, 77%, and 63% in low-, middle-, and high-mortality countries, respectively, alongside RotaTeq vaccine, which was likely effective among children younger than 12 months [33]. The introduction of the rotavirus vaccine in Latin America resulted in a decline in the proportion of diarrhea cases caused by rotavirus from 24.3% to 16.1% [34]. In terms of effectiveness, Rotarix was found to prevent 84% of severe rotavirus diarrhea cases and possibly 41% of cases of severe all-cause diarrhea after one year of follow-up, while RotaTeq prevented 92% of severe rotavirus diarrhea cases. In low-mortality countries, Rotarix was found to prevent 82% of severe rotavirus diarrhea cases and possibly 37% of severe all-cause diarrhea episodes in children vaccinated and followed up for two years, whereas RotaTeq prevented 82% of severe rotavirus diarrhea cases [35]. Because our hospital serves as a referral center for areas hosting many unvaccinated refugees, their inclusion may have diluted the apparent vaccine effect.

The duration of the study (over 5 years) starting with the introduction of the vaccination is not the best way to assess the vaccination effect. Although it is noticeable that Rota AGE decreased each year compared with previous years. A panoramic view of the results of the present study and older studies in Jordan shows almost a 6% drop in the incidence of rotaviral AGE post-vaccine administration. In our cohort over the six years of the study, a steady drop in the rate of AGE was noticed. A 50% reduction was noticed between 2015 and 2020. All in all, the significant protection provided by these vaccines, coupled with the low risk of serious adverse events, highlights the importance of their use.

The study still carries a spectrum of limitations, mainly reassembled by its retrospective nature. Laboratory tests included were routinely performed, with no thorough microbiological assessment, leading to many unidentified etiologies for AGE. E. histolytica identification was mainly through microscopy, which carries low sensitivity. The lack of comprehensive genetic screening for all viruses contributed significantly to unlabeled AGE cases. The study data is only applied to a specific time period (5 years), and its results could not be generalized across other time frames. Further national surveys and screening studies are warranted to confirm the obtained results.

The infection of rotavirus has been associated with severe dehydration, leading to increased levels of hematocrit, urea, creatinine, and serum Na⁺. While the administration of the rotavirus vaccine appeared to reduce the incidence of rotavirus-related AGE, this observation requires prospective controlled studies to confirm the extent of its impact. Additionally, the observed decrease in rotavirus cases may reflect broader trends or other contributing factors that warrant additional research. Continued rotavirus surveillance remains essential, and expanding diagnostic capabilities for other enteric viruses in Jordan will improve case attribution and guide preventive strategies.

There is no funding to report.

Data are available upon request from the corresponding author. The data collection sheets used are available in the appendix for use.

None.