Ehsanipour F; Noorbakhsh S; Taj FE; Movahedi Z

Special Article - Pediatric Gastroenterology

J Pediatr & Child Health Care. 2017; 2(2): 1017.

The Study of Incidence, Clinical Presentation and Progression of Rota Virus Infection in Hospitalized Children with Acute Nonbacterial Diarrhea: A Cross Sectional Study in Tehran, Iran

Ehsanipour F¹, Noorbakhsh S¹*, Taj FE¹ and Movahedi Z²

¹Department of Pediatric Infectious Diseases, Iran University of Medical Sciences, Iran

²Department of Pediatric Infectious Diseases, Qom University of Medical Sciences and Health Services, Iran

*Corresponding author: Samileh Noorbakhsh, Pediatric Infectious Diseases Department, 4th Floor, Rasoul Akram Hospital, Niayesh Street, Satarkhan Avenue, Tehran, Iran

Received: August 30, 2017; Accepted: September 13, 2017; Published: September 20, 2017

Abstract

Background: Rotavirus infection is the most common cause of acute diarrhea in children. Main goal of this study was to determine the incidence, clinical presentation and progression of Rota virus infection in hospitalized children with acute non bacterial diarrhea.

Methods: In a prospective cross sectional study, we studied 80 children with acute onset of non bacterial diarrhea in the pediatric ward of Rasoul Akram Hospital (2011-2013), Tehran, The presence of rotavirus antigen in stool were studied.

Results: Thirty nine (48.8percent) have positive tests for rotavirus. Incidence of rotavirus diarrhea in males was more than female patients, 76.9% of rotavirus diarrhea was observed in cases younger than 18 months. Also, degree of dehydration in children with rotavirus diarrhea was more severe than other cases.

Conclusion: Due to massive unvaccinated infants in Iran, until to mass vaccination, Rotavirus screening tests seems to be necessary in children with acute diarrhea in our young population. Considering the high incidence of rotavirus infection in children with acute diarrhea, Further cost benefit study for rota virus vaccination is needed.

Keywords: Acute diarrheal disease; Viral gastroenteritis; Rota virus; Vaccine

Introduction

According to World Health Organization (WHO) report, 1.5 million deaths annually are due to acute diarrhea in young population [1]. Diarrheal disease is a major cause of malnutrition in children [2]. Viral diarrhea is a major cause of morbidity in childhood and leaded to be hospital admission even in developed countries [3-6]. Although different types of viruses such as norovirus, astrovirus, adenovirus, enterovirus, parechovirus causes acute diseases but rotavirus is known as a common cause in pediatric group [3-18].

Acute Diarrheal Disease (ADD) is a common cause of hospital admission in our country [19,20]. In countries like Iran, which rotavirus vaccination in not used, knowledge of viral etiological agents of, acute diarrheal disease is so important. Rota virus is so important for strategic planning [21-22]. It might be useful for future vaccine development in the region. Shokrollahi et al. showed that viral agents, especially rotavirus (48.8%), HPeV-1 (23.2%) and adenovirus (20%) are the most important causes for viral AGE in children while HBoV (8%) is infrequent during childhood. Determination of various viral pathogens of ADD is very important in planning diarrhea disease control strategies in our country where rotavirus vaccination in not routinely used [23]. Epidemiological aspects of rotavirus in children with acute diarrhea in Tehran and Ahwaz (south of Iran) had reported by some authors [24,25]. In a recent study by Talachial et al. lower level for serum 25(OH) vitamin D in children with acute diarrhea reported [26].

Main goal of this study was to determine the incidence, clinical presentation and progression of Rota virus infection in hospitalized children with acute non bacterial diarrhea during 2 years.

Methods

This study prospective cross sectional study on 80 hospitalized children with acute non bacterial diarrhea in a third level referral hospital (Rasoul Akram, Tehran, Iran) during 2 years.

This study was approved by the Ethics Committee of the Research Center of Pediatric Infectious Diseases at Iran University of Medical Sciences. Data collection was performed after obtaining parental consent.

Definition of cases

In the first step all children with acute infectious diarrheal diseases were selected. For each case, the questionnaire was completed by an authorized physician, covering different aspects such as age, gender and other relevant demographic variables. Clinical manifestations included vomiting, duration and type of diarrhea, duration of hospitalization and finally the lab test results (stool direct exams, biochemical parameters, complete blood count, stool culture and direct viral test in stool). The cases then underwent a thorough clinical exam.

Based on type of diarrheal, medical history, clinical symptoms and examination, stool analysis and lab results (stool exam and culture) and other lab results were selected as cases with non bacterial diarrheal diseases.

Exclusion criteria

Malnutrition, chronic diarrhea, other underlying diseases (malnutrition diabetes, immune deficiency, etc), antibiotic use longer than a month, Cases with bacterial ( based on stool culture ) or other known causes (except viral causes) for stool direct smear (parasitic, amebic toxins, antibiotic associated diarrhea, celiac inflammatory diseases, lactase deficiency etc.) or parenteral (urinary infection, pneumonia, otitis media, sinusitis etc.) were considered as non viral infectious causes and excluded from the study.

Laboratory exam

Stool samples were processed to detect rota and adenoviruses. A rapid chromatographic test was performed with RFDA QUICK Rotavirus/(R-Bio pharm, Germany, N1002) according to the manufacturer’s instructions. At the same time, a part of the stool samples was collected on viral transport media.

Statistical analysis

The student’s t test was used to determine significant in means for continuous variables. The mann whitney u test and the chi-square test were used to compare groups. p-value less than 0.05 were considered statistically significant. The analyses were performed using the SPSS software (Version 11.5).

Results

The range of age in studied cases (n=80) was between 2-108 month; mean age=19.5±21.2 months; 52.5% were (n=42) male and 42.5 (n= 38) were female. Duration of diarrhea: Mean=6.3±4.9 days. Other clinical signs in cases: Fever (T>38) 47.5% (n=38); Vomiting: 42.5% (n=34); Respiratory symptoms: 16.3% (n=16). Positive Rota virus test detected in 48.8% (n=39) of cases with higher rate in male gender (p=0.003); and younger age. (P=0.03, CI=-13.4, 5.5); almost 76.9% cases aged between 1-18 month. The characteristic signs compared between Rotavirus positive and negative cases in Table 1. Except for severity of dehydration which was more common in positive rota virus cases (p=0.001). No significant difference observed for other signs (fever, vomiting, Respiratory symptoms) between 2 groups (Figure 1).

Table 1: Comparison of the characteristic signs between Rotavirus positive and negative cases. Case group (n=25) Control group (n=25) p.




  
    Clinical signs in Rota 
    Positive Rota virus test 
    Negative Rota virus test 
    P value 
  
  
    Male/female ratio 
    27/12
    15/26
    0.003 
  
  
    Mean    age 
    17.49 months
    21.44 months
    0.03 
  
  
    Duration    of diarrhea:
    Mean=6.3±4.9 days
    Mean=6.3±4.9 days
     
  
  
    Fever    (T>38) 
    53.8%(n=21)
    41%(n=17)
    0.07
  
  
    Vomiting 
    48.7 %(n=19)
    36%(n=15)
    0.3
  
  
    Respiratory    symptoms
    5
    8
    0.5
  
  
    Duration    of diarrhea:
    Mean=6.82±5.9 days
    Mean=5.8±3.7 days
    0.6
  
  
    Severity    of dehydration 
    No:11
      Mild:12
      Moderate:13
      Severe:3
    No:24
      Mild:15
      Moderate:1
      Severe:1
    0.001



Table 1: Comparison of the characteristic signs between Rotavirus positive and
negative cases. Case group (n=25) Control group (n=25) p.

Figure 1: Age histogram of studied cases.

    
    
    Figure 1:  Age histogram of studied cases.

Discussion

In this study upon 80 cases with acute non bacterial diarrhea during 2 years. Here we found Positive Rota virus test in stool specimen of 48.8% (n=39) cases. Rota virus infection had the higher rate in male gender (p=0.003); and younger age (p=0.03). Near most cases (76.9%) were younger than 18 month. Except for severity of dehydration which was more common in positive rota virus cases (p=0.001). No significant difference observed for other signs (fever, vomiting, Respiratory symptoms) between 2 groups.

Like here, rota virus antigen obtained from stool of ADD cases between 15-47% of hospitalized children with Acute Diarrheal Disease, just in 12% of controls group. Adenovirus and astrovirus obtained from stool of Iranian children with AGE [11-21]. Saderi et al. reported the incidence of enteric adenoviruses in Iranian children. 6.7% of stool specimens contained enteric adenoviruses (3.3% Ad40 and 3.4% Ad41) and 2.0% non-enteric adenoviruses [14].

Like other studies Rotavirus was the most common cause for viral AGE in near 60% of studied cases (48% single isolate and 12% coinfection with adenovirus). Adenovirus (20%); Human Boca virus (8%); coinfection Adeno & Rota (6%) diagnosed respectively. 12% was undiagnosed.

The probable viral causes might be norovirus, astrovirus or others.

The isolation rate for HBoV (6%) was significanltly lower (P<0.0006) than Rota; and Adenovirus (p=0.0001).

This study is close to a Korean study (10); 44.7% of all AGE cases was viral; rotavirus (25.7%), norovirus (13.7%), adenovirus (3.0%), astrovirus (1.1%), and human bocavirus (0.8%) [10].

Rotavirus is a common cause of acute gastroenteritis in Iranian children [11,14].

In Present study, 60% Rota virus positive (48% as single and 12% coinfection with adenovirus) is very close to Esteghamati et al. upon 1298 stool samples with diarrhea [14], They found 59.1% positive test for rotavirus in all diarrheal diseases. 85% occurred during the first 2 years of life, and peak prevalence of severe rotavirus disease occurring from September through January. 30.9% of strains (110 positive rotavirus) G4P [8] was the most commonly detected rotavirus genotype P [8] with G nontypeable (21.8%), G4 with P nontypeable (13.6%), G1 [P8] (10.9%), and G2 [P4] (5.5%) [14]. But Zamani et al. reported [11] very lower rate for rotavirus antigen (15.3%). Kazemi et al. [13] compared 185 hospitalized children with acute diarrhea and 91 controls; positive rotavirus antigens obtained from 30.8% of acute diarrhea and 12.1% of control children (p<0.05). Hosseininasab et al. reported the etiologic causes of aseptic meningitis in CSF of 65 Iranian children with by PCR, 30 (46.2%) were positive for the viruses. A virus was detected in 30 (46.2%). Non-polio human enterovirus and mumps virus were detected in 13 (43.3%) and 11 (36.7%) respectively. Mumps meningitis was found in two vaccinated and nine non-vaccinated patients [22]. Although evidence suggesting that rotavirus is a cause of central nervous system sequelae remains inconclusive [3,7]. A search of 2 large hospital discharge databases suggested that seizures are noted as part of the discharge diagnosis in the records of, at most, <4% of patients with rotavirus diarrhea versus 7% of patients with bacterial diarrhea [3-5]. 16% of AGE in present study had neurologic manifestations (seizure: 12%; aseptic meningitis: 4%), 20% of adenoviral, 13.5% of rota virus and 33.3% of coinfection, none of Human Boca virus presented with neurologic signs but without significant differences (P=0.619). Lynch et al. explained 2 patients with rotavirus gastroenteritis who developed encephalopathy, rotavirus RNA was detected in the Cerebro Spinal Fluid (CSF) by reverse transcription-polymerase chain reaction; in 1 patient, rotavirus RNA was detected on 2 occasions 3 weeks apart. Is it a true pathogen? CSF contamination that occurs at the time of lumbar puncture or in the laboratory, or carriage of rotavirus RNA in trafficking lymphocytes is another explanation [3]. Nakagomi et al. study Rotavirus antigen was detected in acute phase sera from 5 of 8 children with rotavirus-associated encephalopathy, confirming antigenemia. However, antigenemia was not detected in cerebrospinal fluid, failing to provide added evidence of invasion to the brain.

Here, the adenovirus detection is higher than 2 previous Iranian studies [14,15]. Saderi et al. study obtained enteric adenoviruses in 6.7% (3.3% Ad40 and 3.4% Ad41) and nonenteric adenoviruses 2.0%; from stool samples of AGE cases [14]. Modaress et al. study (2004) showed adenoviruses (Ad40, 41) 2.6% of AGE cases, but not in healthy control group [15]. Hamkar et al. study determined the rate of positive Rotavirus, adenovirus and astrovirus 62%, 2.3%, and 3% of samples, respectively. Astrovirus and adenovirus were detected predominantly in the 2-5-year-old age group of children, with a prevalence of 8.3% and 3.5% respectively. All studied viral gastroenteritis peaked in the winter, and minimum rate were found in summer [16].

Results of the Hamkar et al. study (2006) upon 400 symptomatic cases with acute gastroenteritis in Mazandaran Province (north of Iran) showed rotavirus: 62%, adenovirus 2.3%, and astrovirus3%. Astrovirus and adenovirus detected predominantly in the age; 2-5-years and rotaviruses was in the <1-year old age group of children [16]. In contrast to it, we found higher rate of adenovirus (20% and 12%) in AGE cases. The prevalence of astrovirus infection was estimated to be between 2 to 16% among hospitalized children with diarrhea in other countries, and 3% in Iran (Mazandran) but not studied in present study.

Although evidence suggesting that rotavirus is a cause of central nervous system squeal remains inconclusive [4-6]. Rotavirusassociated encephalopathy described by some authors. Nakagomi et al. study [7] determined the rotavirus antigen in acute phase sera from 5 of 8 children with rotavirus-associated encephalopathy, confirming antigenemia, but not in cerebrospinal fluid, failing to provide added evidence of invasion to the brain [7]. There are increasing reports of cases in which patients who have seizures after an episode of rotavirus diarrhea have evidence of rotavirus in their CSF [3].

Conclusion

Due to massive unvaccinated infants in Iran, until to mass vaccination, Rotavirus screening tests seems to be necessary in children with acute diarrhea in our young population. Considering the high incidence of rotavirus infection in children with acute diarrhea, further cost benefit study for rota virus vaccination is needed.

References

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Citation: Ehsanipour F, Noorbakhsh S, Taj FE and Movahedi Z. The Study of Incidence, Clinical Presentation and Progression of Rota Virus Infection in Hospitalized Children with Acute Nonbacterial Diarrhea: A Cross Sectional Study in Tehran, Iran. J Pediatr & Child Health Care. 2017; 2(2): 1017.

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